Utilizing In-Hospital Fabrication to Decrease Simulation Costs.

BACKGROUND: Two restrictive factors for surgical training through simulation, are the cost of and accessibility to materials and consoles for simulation models. Commercial surgical simulation models continue to maintain high prices with a wide range of fidelity levels. We believe that by utilizing in-house fabrication, these barriers can be decreased while maintaining and even improving the functionality of surgical simulation models as well as increase their individualization and customization. METHODS: By using a combination of digital and manual fabrication techniques such as 3D printing and basic mold making methods, we were able to create models equivalent to current commercial products by utilizing the first of its kind MakerHEALTH space and collaborating with our surgical simulation staff. We then compared our research and development, start-up, materials, operational, and labor costs to buying comparable commercial models with the simulation usage rates of our institution. RESULTS: We were able to decrease the costs of a 6 model simulation sample set (appendectomy, cholecystectomy, common bile duct exploration, ventral hernia, chest tube insertion, and suture pads) at our institution from $99,646.60 to $13,817.21 for a medical student laborer, $14,500.56 for a surgical resident laborer, $15,321.08 for a simulation staff laborer, and $18,984.48 for an attending physician laborer. CONCLUSION: We describe successful approaches for the creation of cost-effective and modular simulation models with the aim of decreasing the barriers to entry and improving surgical training and skills. These techniques make it financially feasible for learners to train during larger faculty-led workshops and on an individual basis, allowing for access to simulation at any time or place.

Evaluation of ES-derived neural progenitors as a potential source for cell replacement therapy in the gut.

BACKGROUND: Stem cell-based therapy has recently been explored for the treatment of disorders of the enteric nervous system (ENS). Pluripotent embryonic stem (ES) cells represent an attractive cell source; however, little or no information is currently available on how ES cells will respond to the gut environment. In this study, we investigated the ability of ES cells to respond to environmental cues derived from the ENS and related tissues, both in vitro and in vivo. METHODS: Neurospheres were generated from mouse ES cells (ES-NS) and co-cultured with organotypic preparations of gut tissue consisting of the longitudinal muscle layers with the adherent myenteric plexus (LM-MP). RESULTS: LM-MP co-culture led to a significant increase in the expression of pan-neuronal markers (ßIII-tubulin, PGP 9.5) as well as more specialized markers (peripherin, nNOS) in ES-NS, both at the transcriptional and protein level. The increased expression was not associated with increased proliferation, thus confirming a true neurogenic effect. LM-MP preparations exerted also a myogenic effect on ES-NS, although to a lesser extent. After transplantation in vivo into the mouse pylorus, grafted ES-NS failed to acquire a distinct phenotype al least 1 week following transplantation. CONCLUSIONS: This is the first study reporting that the gut explants can induce neuronal differentiation of ES cells in vitro and induce the expression of nNOS, a key molecule in gastrointestinal motility regulation. The inability of ES-NS to adopt a neuronal phenotype after transplantation in the gastrointestinal tract is suggestive of the presence of local inhibitory influences that prevent ES-NS differentiation in vivo.

Predicting and enhancing American Board of Surgery In-Training Examination performance: does writing questions really help?

BACKGROUND: The generative learning model posits that individuals remember content they have generated better than materials created by others. The goals of this study were to evaluate question generation as a study method for the American Board of Surgery In-Training Examination (ABSITE) and determine whether practice test scores and other data predict ABSITE performance. METHODS: Residents (n = 206) from 6 general surgery programs were randomly assigned to one of the two study conditions. One group wrote questions for practice examinations. All residents took 2 practice examinations. RESULTS: There was not a significant effect of writing questions on ABSITE score. Practice test scores, United States Medical Licensing Examination Step 1 scores, and previous ABSITE scores were significantly correlated with ABSITE performance. CONCLUSIONS: The generative learning model was not supported. Performance on practice tests and other data can be used for early identification of residents at risk of performing poorly on the ABSITE.

Influence of stochastic gene expression on the cell survival rheostat after traumatic brain injury.

Experimental evidence suggests that random, spontaneous (stochastic) fluctuations in gene expression have important biological consequences, including determination of cell fate and phenotypic variation within isogenic populations. We propose that fluctuations in gene expression represent a valuable tool to explore therapeutic strategies for patients who have suffered traumatic brain injury (TBI), for which there is no effective drug therapy. We have studied the effects of TBI on the hippocampus because TBI survivors commonly suffer cognitive problems that are associated with hippocampal damage. In our previous studies we separated dying and surviving hippocampal neurons by laser capture microdissection and observed unexplainable variations in post-TBI gene expression, even though dying and surviving neurons were adjacent and morphologically identical. We hypothesized that, in hippocampal neurons that subsequently are subjected to TBI, randomly increased pre-TBI expression of genes that are associated with neuroprotection predisposes neurons to survival; conversely, randomly decreased expression of these genes predisposes neurons to death. Thus, to identify genes that are associated with endogenous neuroprotection, we performed a comparative, high-resolution transcriptome analysis of dying and surviving hippocampal neurons in rats subjected to TBI. We found that surviving hippocampal neurons express a distinct molecular signature--increased expression of networks of genes that are associated with regeneration, cellular reprogramming, development, and synaptic plasticity. In dying neurons we found decreased expression of genes in those networks. Based on these data, we propose a hypothetical model in which hippocampal neuronal survival is determined by a rheostat that adds injury-induced genomic signals to expression of pro-survival genes, which pre-TBI varies randomly and spontaneously from neuron to neuron. We suggest that pharmacotherapeutic strategies that co-activate multiple survival signals and enhance self-repair mechanisms have the potential to shift the cell survival rheostat to favor survival and therefore improve functional outcome after TBI.

Neural stem cell transplantation in the stomach rescues gastric function in neuronal nitric oxide synthase-deficient mice.

BACKGROUND & AIMS: Nitric oxide is a major inhibitory neurotransmitter in the enteric nervous system. Loss or dysfunction of nitrinergic neurons is associated with serious disruptions of motility, intractable symptoms, and long-term suffering. The aim of this study was to evaluate the effect of intrapyloric transplantation of neural stem cells (NSCs) on gastric emptying and pyloric function in nNOS-/- mice, a well-established genetic model of gastroparesis. METHODS: NSCs were isolated from embryonic mice transgenically engineered to express green fluorescent protein and transplanted into the pylorus of nNOS-/- mice. Grafted cells were visualized in pyloric sections and further characterized by immunofluorescence staining. One week posttransplantation, gastric emptying to a non-nutrient meal was measured using the phenol red method and pyloric function was assessed by measuring the relaxation of pyloric strips in an organ bath in response to electrical field stimulation (EFS) under nonadrenergic, noncholinergic conditions. RESULTS: One week following implantation, grafted NSCs differentiated into neurons and expressed neuronal nitric oxide synthase. Gastric emptying was significantly increased in mice that received NSCs as compared with vehicle-injected controls (49.67% vs 35.09%; P < .01 by Student t test). EFS-induced relaxation of pyloric strips was also significantly increased (P < .01 by 2-way analysis of variance). The nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester and the neuronal blocker tetrodotoxin blocked the EFS-induced relaxation, indicating that the observed effect is NO mediated and neuronally derived. CONCLUSIONS: Our results support the potential of NSC transplantation as a viable therapeutic option for neuroenteric disorders.