Comparación de los programas de residencia en urología de Estados Unidos y China / Comparison of urology residency training between the United States and China

Objetivo: Este estudio compara el estado actual y las características de los programas de formación de la residencia de urología de EE. UU. y China.Métodos: Se realizó una evaluación comparativa de la trayectoria, la estructura, el plan de estudios, la experiencia quirúrgica, las actividades académicas, los sistemas de evaluación y otros aspectos de la formación de los residentes en China y EE. UU.Resultados: Los programas de residencia de urología de China y EE. UU. difieren entre sí en muchos aspectos. Los requisitos de acceso al programa de residencia de urología de EE. UU. son más rigurosos, y la especialización de la formación en EE. UU. está más condensada. Además, en EE. UU. la formación clínica e investigativa es más práctica y el sistema de evaluación es más diverso y basado en competencias. Adicionalmente, las oportunidades laborales tras la residencia difieren sustancialmente entre estos dos países. Convertirse en cirujano urológico independiente no es el objetivo específico de la formación de la residencia urológica en China, y esto requiere mucho más tiempo de formación que en EE. UU.Conclusión: Los programas de residencia de urología en EE. UU. y China tienen un formato y unas características propias. La formación en China se centra en técnicas y procedimientos generales, mientras que los programas en EE. UU. siguen un plan de estudios más estandarizado. Tanto EE. UU. como China pueden ser un buen complemento para la creación de programas de formación que, en última instancia, proporcionen una atención de alta calidad a los pacientes (AU)

Objective: This study compares the present status and traits of urology residency programs in the United States and China.Methods: The flow path, structure, curriculum, operative experience, scholarly activities, evaluation systems and other aspects of training were comparatively evaluated between China and the United States.Results: Urology residency training programs are different between China and the United States in many aspects. Admission requirements for the United States urology residency program are more rigorous, and the specialty training program in the United States is more concentrated. Furthermore, residency programs in USA have much more practical clinical and research training, and their evaluation process is more diverse, and it has been designed to assess competencies. Moreover, job opportunities after residency substantially differ between these two countries. Becoming an independent urologic surgeon is not the specific goal of the Urology residency training program in China, and it would require more training time than in the United States.Conclusion: Urology residency training programs in the United States and China have a unique format and characteristics. The training programs in China are focused on general techniques and procedures, while training programs in USA follow a more standardized curriculum. Both USA and China may complement each other to create training programs that would ultimately provide high-quality patient care (AU)

Comparison of urology residency training between the United States and China.

OBJECTIVE: This study compares the present status and traits of urology residency programs in the United States and China. METHODS: The flow path, structure, curriculum, operative experience, scholarly activities, evaluation systems and other aspects of training were comparatively evaluated between China and the United States. RESULTS: Urology residency training programs are different between China and the United States in many aspects. Admission requirements for the United States urology residency program are more rigorous, and the specialty training program in the United States is more concentrated. Furthermore, residency programs in USA have much more practical clinical and research training, and their evaluation process is more diverse, and it has been designed to assess competencies. Moreover, job opportunities after residency substantially differ between these two countries. Becoming an independent urologic surgeon is not the specific goal of the Urology residency training program in China, and it would require more training time than in the United States. CONCLUSION: Urology residency training programs in the United States and China have a unique format and characteristics. The training programs in China are focused on general techniques and procedures, while training programs in USA follow a more standardized curriculum. Both USA and China may complement each other to create training programs that would ultimately provide high-quality patient care.

Human Cortex Spheroid with a Functional Blood Brain Barrier for High-Throughput Neurotoxicity Screening and Disease Modeling.

The integral selectivity characteristic of the blood brain barrier (BBB) limits therapeutic options for many neurologic diseases and disorders. Currently, very little is known about the mechanisms that govern the dynamic nature of the BBB. Recent reports have focused on the development and application of human brain organoids developed from neuro-progenitor cells. While these models provide an excellent platform to study the effects of disease and genetic aberrances on brain development, they may not model the microvasculature and BBB of the adult human cortex. To date, most in vitro BBB models utilize endothelial cells, pericytes and astrocytes. We report a 3D spheroid model of the BBB comprising all major cell types, including neurons, microglia and oligodendrocytes, to recapitulate more closely normal human brain tissue. Spheroids show expression of tight junctions, adherens junctions, adherens junction-associated proteins and cell specific markers. Functional assessment using MPTP, MPP+ and mercury chloride indicate charge selectivity through the barrier. Junctional protein distribution was altered under hypoxic conditions. Our spheroid model may have potential applications in drug discovery, disease modeling, neurotoxicity and cytotoxicity testing.

Ibuprofen loaded PLA nanofibrous scaffolds increase proliferation of human skin cells in vitro and promote healing of full thickness incision wounds in vivo.

This article presents successful incorporation of ibuprofen in polylactic acid (PLA) nanofibers to create scaffolds for the treatment of both acute and chronic wounds. Nanofibrous PLA scaffolds containing 10, 20, or 30 wt % ibuprofen were created and ibuprofen release profiles quantified. In vitro cytotoxicity to human epidermal keratinocytes (HEK) and human dermal fibroblasts (HDF) of the three scaffolds with varying ibuprofen concentrations were evaluated and compared to pure PLA nanofibrous scaffolds. Thereafter, scaffolds loaded with ibuprofen at the concentration that promoted human skin cell viability and proliferation (20 wt %) were evaluated in vivo in nude mice using a full thickness skin incision model to determine the ability of these scaffolds to promote skin regeneration and/or assist with scarless healing. Both acellular and HEK and HDF cell-seeded 20 wt % ibuprofen loaded nanofibrous bandages reduced wound contraction compared with wounds treated with Tegaderm™ and sterile gauze. Newly regenerated skin on wounds treated with cell-seeded 20 wt % ibuprofen bandages exhibited significantly greater blood vessel formation relative to acellular ibuprofen bandages. We have found that degradable anti-inflammatory scaffolds containing 20 wt % ibuprofen promote human skin cell viability and proliferation in vitro, reduce wound contraction in vivo, and when seeded with skin cells, also enhance new blood vessel formation. The approaches and results reported here hold promise for multiple skin tissue engineering and wound healing applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 327-339, 2017.

Assessments of injectable alginate particle-embedded fibrin hydrogels for soft tissue reconstruction.

Soft tissue reconstruction is often needed after massive traumatic damage or cancer removal. In this study, we developed a novel hybrid hydrogel system consisting of alginate particles and a fibrin matrix that could maintain tissue volume long term. Alginate particles were fabricated by mixing 5% alginate with a 20 mM calcium solution. Cells and these alginate particles were then embedded in fibrin (alginate-fibrin) hydrogels using a dual syringe mixer. Cell-hydrogel constructs were evaluated in terms of cell survival and proliferation in the constructs in vitro. The results indicated that cellular viability, spreading and proliferation in the alginate-fibrin hydrogels were significantly higher compared to constructs fabricated with fibrin or alginate only. In vivo explants showed that cells contained within fibrin-only hydrogels did not contribute to neo-tissue formation, and the fibrin was fully degraded within a 12 week period. In the alginate-fibrin system, higher cellularity and vascular ingrowth were observed in vivo. This resulted in neo-tissue formation in the alginate-fibrin hydrogels. These results demonstrate that fibrin may enhance cell proliferation and accelerate the formation of extracellular matrix proteins in the alginate-fibrin system, while the alginate particles could contribute to volume retention. This injectable hybrid system composed of degradable and non-degradable hydrogels may be a preferable approach to the repair of soft tissue defects.

Decellularization for whole organ bioengineering.

Organ transplantation in an orthotopic location is the current treatment for end-stage organ failure. However, the need for transplantable organs far exceeds the number of available donor organs. As a result, new options, such as tissue engineering and regenerative medicine, have been explored to achieve functional organ replacement. Although there have been many advances in the laboratory leading to the reconstruction of tissue and organ structures in vitro, these efforts have fallen short of producing organs that contain intact vascular networks capable of nutrient and gas exchange and are suitable for transplantation. Recently, advances in whole organ decellularization techniques have enabled the fabrication of scaffolds for engineering new organs. These scaffolds, consisting of naturally-derived extracellular matrix (ECM), provide biological signals and maintain tissue microarchitecture, including intact vascular systems that could integrate into the recipient's circulatory system. The decellularization techniques have led to the development of scaffolds for multiple organs, including the heart, liver, lung and kidney. While the experimental studies involving the use of decellularized organ scaffolds are encouraging, the translation of whole organ engineering into the clinic is still distant. This paper reviews recently described techniques used to decellularize whole organs such as the heart, lung, liver and kidney and describes possible methods for using these matrices for whole organ engineering.

Controlled heparin conjugation on electrospun poly(ε-caprolactone)/gelatin fibers for morphology-dependent protein delivery and enhanced cellular affinity.

Electrospun fibrous scaffolds have now been shown to possess great potential for tissue engineering applications, owing to their unique mimicry of natural extracellular matrix structure. In this study, poly(ε-caprolactone) and gelatin were electrospun to fabricate tissue-engineered scaffolds with three different fiber morphologies (1.0 µm, 3.0 µm and co-electrospun containing both 1.0 and 3.0 µm diameter fibers). Subsequently, these scaffolds were conjugated with heparin to immobilize a bioactive molecule by electrostatic interactions. This study determined the quantity of heparin conjugation on the scaffolds and that the crosslinking time and the fiber morphologies govern the extent of heparin conjugation on the fibers. In order to evaluate the release capacity of the heparin-conjugated scaffolds, lysozyme was used as a model protein for conjugation. The heparin-conjugated scaffolds provided high loading efficiency and cumulative release of lysozyme with a relatively linear relationship. In addition, the release kinetics was significantly dependent on heparin conjugation and fiber morphology. This fundamental investigation into how fiber morphology and crosslinking protocols can affect the heparin binding ability of electrospun fibers is crucial for predicting the delivery of many different types of bioactive molecules from an electrospun scaffold for tissue engineering applications.

Embryoid body formation of human amniotic fluid stem cells depends on mTOR.

Human amniotic fluid stem cells (hAFSCs) harbor high proliferative capacity and high differentiation potential and do not raise the ethical concerns associated with human embryonic stem cells. The formation of three-dimensional aggregates known as embryoid bodies (EBs) is the principal step in the differentiation of pluripotent embryonic stem cells. Using c-Kit-positive hAFSC lines, we show here that these stem cells harbor the potential to form EBs. As part of the two kinase complexes, mTORC1 and mTORC2, mammalian target of rapamycin (mTOR) is the key component of an important signaling pathway, which is involved in the regulation of cell proliferation, growth, tumor development and differentiation. Blocking intracellular mTOR activity through the inhibitor rapamycin or through specific small interfering RNA approaches revealed hAFSC EB formation to depend on mTORC1 and mTORC2. These findings demonstrate hAFSCs to be a new and powerful biological system to recapitulate the three-dimensional and tissue level contexts of in vivo development and identify the mTOR pathway to be essential for this process.

Basic science research in urology training.

The role of basic science exposure during urology training is a timely topic that is relevant to urologic health and to the training of new physician scientists. Today, researchers are needed for the advancement of this specialty, and involvement in basic research will foster understanding of basic scientific concepts and the development of critical thinking skills, which will, in turn, improve clinical performance. If research education is not included in urology training, future urologists may not be as likely to contribute to scientific discoveries.Currently, only a minority of urologists in training are currently exposed to significant research experience. In addition, the number of physician-scientists in urology has been decreasing over the last two decades, as fewer physicians are willing to undertake a career in academics and perform basic research. However, to ensure that the field of urology is driving forward and bringing novel techniques to patients, it is clear that more research-trained urologists are needed. In this article we will analyse the current status of basic research in urology training and discuss the importance of and obstacles to successful addition of research into the medical training curricula. Further, we will highlight different opportunities for trainees to obtain significant research exposure in urology.

Expression-targeted gene therapy for the treatment of transitional cell carcinoma.

Targeted gene delivery for induced apoptosis of transitional cell carcinomas was carried out in vivo in mice via utilization of the murine cyclooxygenase type 2 (Cox-2) promoter (Tis10). MB49 cells, which constitutively overexpress Cox-2 like numerous other carcinomas, selectively expressed delivered genes that utilized this transcriptional control element. The products of the delivered genes were artificially inducible forms of caspases 3 and 9, which remained inactive until a chemical inducer of dimerization was later injected intraperitoneally. The genes were delivered intravesically as plasmids complexed with poly(ethylenimine). Significant improvements, in the form of reduced bladder mass, reduced tumor volume, anti-angiogenesis and inhibition of tumor growth were seen versus untreated or unactivated controls. In some instances, tumors were seen to go into complete remission. There were no apparent bystander effects associated with the treatments. This targeted gene therapy regimen could have wide applicability to numerous cancers due to constitutive overexpression of Cox-2.

Renal differentiation of amniotic fluid stem cells.

OBJECTIVES: The role of stem cells in regenerative medicine is evolving rapidly. Here, we describe the application, for kidney regeneration, of a novel non-genetically modified stem cell, derived from human amniotic fluid. We show that these pluripotent cells can develop and differentiate into de novo kidney structures during organogenesis in vitro. MATERIALS AND METHODS: Human amniotic fluid-derived stem cells (hAFSCs) were isolated from human male amniotic fluid obtained between 12 and 18 weeks gestation. Green fluorescent protein and Lac-Z-transfected hAFSCs were microinjected into murine embryonic kidneys (12.5-18 days gestation) and were maintained in a special co-culture system in vitro for 10 days. Techniques of live microscopy, histology, chromogenic in situ hybridization and reverse transcriptase polymerase chain reaction were used to characterize the hAFSCs during their integration and differentiation in concert with the growing organ. RESULTS: Green fluorescent protein and Lac-Z-transfected hAFSCs demonstrated long-term viability in organ culture. Histological analysis of injected kidneys revealed that hAFSCs were capable of contributing to the development of primordial kidney structures including renal vesicle, C- and S-shaped bodies. Reverse transcriptase polymerase chain reaction confirmed expression of early kidney markers for: zona occludens-1, glial-derived neurotrophic factor and claudin. CONCLUSIONS: Human amniotic fluid-derived stem cells may represent a potentially limitless source of ethically neutral, unmodified pluripotential cells for kidney regeneration.

Tunica repair with acellular bladder matrix maintains corporal tissue function.

Penile conditions, such as Peyronie's disease or tumor resection may require surgical reconstruction of the tunica albuginea. Various materials have been proposed, as a biomaterial for tunica albuginea repair, however, little functional data are available. We examined the applicability and functional outcome of a collagen-based matrix derived from the bladder (acellular bladder matrix (ABM)), as a biomaterial for tunica repair. Biocompatibility testing was performed on the matrix, which included mitochondrial metabolic activity, cell viability and apoptosis. Approximately 50% of the dorsal penile tunica albuginea was replaced with the collagen-based matrix patch after surgical removal in 24 New Zealand White rabbits. Cavernosometry and cavernosography were performed. The animals were killed 1, 2 and 3 months after surgery for analyses. The matrix showed excellent biocompatibility. All animals implanted with the matrix survived without any noticeable untoward effects. There was no evidence of inflammation or infection at the time of retrieval. Cavernosometry of the implanted animals demonstrated normal intracavernosal pressures with visual erections. Cavernosography of the repaired corpora showed a normal anatomical configuration. Biomechanical analysis of the retrieved matrices demonstrated similar tensile strengths as native tunica. Histologically, there was only a minimal inflammatory response, which gradually decreased over time. These results show that ABM is biocompatible, durable and effective when used as a tunica substitute. The matrix may be useful as an off-the-shelf biomaterial for patients requiring tunica albuginea repair.

The effect of thrombin on ACL fibroblast interactions with collagen hydrogels.

Premature loss of provisional scaffold formation has been identified as one of the factors responsible for poor healing of intraarticular tissues. To address this deficiency, substitute provisional scaffolds are being developed. The function of these scaffolds can be enhanced by the addition of specific extracellular matrix proteins. In this study, it was hypothesized that the addition of thrombin to a provisional scaffold material would result in increases in cell proliferation, collagen production, and cell migration within the scaffold. These three parameters are thought to be critical components of wound healing. Gels containing fibrin and collagen supplemented with either 0, 10.5, 21, or 42 U/mL of thrombin were placed in contact with explants of tissue from the anterior cruciate ligament. The addition of thrombin stimulated cell migration at low concentrations and impaired migration at higher concentrations, and had no significant effect on cell proliferation or collagen production. The use of all concentrations of thrombin resulted in mechanically weaker gels. Thus, the use of thrombin to optimize a collagen-platelet rich plasma (PRP) provisional scaffold must be done with caution, and use of high concentrations of thrombin (>42 IU/mL) should be avoided specifically in situations where gel strength or cell ingrowth is important. Use of low concentrations of thrombin (10.5 IU/mL) may be beneficial in applications where a faster set time and enhanced cell migration are desirable and the gel mechanical strength is of secondary importance.

Tissue engineering for urinary incontinence applications.

Urinary incontinence affects men and women of all ages, and may be present in nearly half of all elderly women. Current nonpharmacologic, pharmacologic, and surgical therapies often only offer short-term relief. This review focuses on the application of tissue engineering and regenerative medicine to the field of urinary incontinence. The principles of tissue engineering will be discussed as well as some current strategies for applying these principles in developing novel therapies for urinary incontinence.

Alterations in angiogenic growth factors and neuronal nitric oxide synthase expression in chronic cavernosal ischemia.

Our aim was to study anatomical and molecular changes at varying time points after the induction of cavernosal ischemia (CI) in a rabbit model of arteriogenic erectile dysfunction. Tissue structure and the expression of angiogenic and neurogenic genes were examined using immunostaining and reverse transcription-polymerase chain reaction (RT-PCR) analyses. We found a progressive increase of erectile connective tissue together with a decrease in smooth muscle cell content as the duration of CI increased. Immunohistochemical staining showed an increase in vascular endothelial growth factor (VEGF) levels at the early stages and a decrease at the later stages of ischemia. RT-PCR analysis of VEGF and neuronal nitric oxide synthase (nNOS) confirmed these results and showed nearly a two-fold increase in VEGF and nNOS mRNA levels in the early stages of CI with a decrease at the later stages of CI. On the other hand, mRNA levels of VEGF receptor, KDR, decreased approximately by 50% over the course of CI. Our studies showed that the cellular and molecular responses of the erectile tissue to short-term ischemia are different than those seen after long-term ischemia. The dramatic reduction in KDR expression suggests that the cavernosal endothelium is very sensitive to ischemia. The similar changes in VEGF and nNOS expression over the course of CI suggest a tissue-defensive mechanism to CI via the VEGF and NO pathways. Taken together, this study suggests that supplementation of VEGF at earlier stages of ischemia may restore the damaged endothelial cells of the corpus cavernosum and support tissue perfusion.

[Tissue engineering in urology. Basic principles and application]. / Tissue engineering in der Urologie. Prinzipien und Anwendung.

Tissue engineering is a rather new field of science. Despite this fact, some experimental investigations have already been applied in clinical studies. Compared to other medical fields, tissue engineering in urology is well established. Tissue-engineered bulking agents and tissue-engineered bladder augments are being investigated in clinical trials. Even though the knowledge gained in recent years is promising, the results of cellular therapies need to be critically judged before being finally applied in patients. Genetic engineering and stem cell research (adult undifferentiated cells) have had major impact on the field of tissue engineering over the past 2 years. By using the technology of genetic engineering, biochemical and functional qualities of tissues may be modified. Adult stem cells may help to substitute lost tissue in an autologous fashion by isolating undifferentiated cells from the body and by differentiating them into a desired cell type. These cells may be used to form native functional tissue to replace a diseased organ or organ part.

Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo.

Arterial conduits are increasingly preferred for surgical bypass because of inherent functional properties conferred by arterial endothelial cells, especially nitric oxide production in response to physiologic stimuli. Here we tested whether endothelial progenitor cells (EPCs) can replace arterial endothelial cells and promote patency in tissue-engineered small-diameter blood vessels (4 mm). We isolated EPCs from peripheral blood of sheep, expanded them ex vivo and then seeded them on decellularized porcine iliac vessels. EPC-seeded grafts remained patent for 130 days as a carotid interposition graft in sheep, whereas non-seeded grafts occluded within 15 days. The EPC-explanted grafts exhibited contractile activity and nitric-oxide-mediated vascular relaxation that were similar to native carotid arteries. These results indicate that EPCs can function similarly to arterial endothelial cells and thereby confer longer vascular-graft survival. Due to their unique properties, EPCs might have other general applications for tissue-engineered structures and in treating vascular diseases.

Vascular endothelial growth factor-mediated autocrine stimulation of prostate tumor cells coincides with progression to a malignant phenotype.

Vascular endothelial growth factor (VEGF), which is often produced at high levels by tumor cells, is a well-known mediator of tumor angiogenesis. VEGF receptor tyrosine kinases, KDR/Flk-1 and Flt-1, have been thought to be expressed exclusively by endothelial cells. In this study, we have used a prostate tumor progression series comprised of a differentiated rat prostate epithelial cell line, NbE-1, and its highly motile clonal derivative, FB2. Injection of NbE-1 cells into the inferior vena cava of syngeneic rats indicated that these cells are nontumorigenic. Using the same model, FB2 cells generated rapidly growing and well-vascularized tumors in the lungs. NbE-1 expressed marginal levels of VEGF, whereas high levels of VEGF protein were detected in FB2-conditioned medium and in FB2 tumors in vivo. Analysis of (125)I-VEGF(165) binding to NbE-1 and FB2 cells indicated that only motile FB2 cells expressed the VEGF receptor Flt-1. Consistent with this finding, physiological concentrations of VEGF induced chemotactic migration in FB2 but not in NbE-1 cells. This is the first documentation of a functional Flt-1 receptor in prostate tumor cells. Our results suggest two roles for VEGF in tumor progression: a paracrine role as an angiogenic factor and a previously undescribed role as an autocrine mediator of tumor cell motility.