There is a need for a peripheral nerve model on which surgeons-in-training can simulate the repair of nerve injuries at their own pace. Although practicing on animal models/cadavers is considered the “gold standard” of microsurgical training, the proposed model aims to provide a platform for improving the technical skills of surgical trainees prior to their practice on cadaver/animal models. In addition, this model has the potential to serve as a standardized test medium for assessing the skill sets of surgeons.
Methods
Several formulations of silicone were utilized for the design and fabrication of a model which realizes the hierarchical structure of peripheral nerves. The mechanical properties were characterized via the Universal Testing Machine; the damage caused by the needle on the entry sites was assessed through scanning electron microscopy (SEM).
Results
Mechanical properties of the formulations of silicone were tested to mimic human peripheral nerves. A formulation with 83.3?wt% silicone oil and 0.1?wt% cotton fiber was chosen to be used as nerve fascicles. Both 83.3?wt% silicone oil with cotton fiber and 66.6?wt% silicone oil without fiber provided a microsuturing response similar to that of epineurium at a wall thickness of 1?mm. SEM also confirmed that the entry of the needle did not introduce significant holes at the microsuturing sites.
Conclusions
The proposed peripheral nerve model mimicked human tissues mechanically and cosmetically, and a simulation of the repair of a fifth-degree nerve injury was achieved. 相似文献
When our own knowledge is limited, we often turn to others for information. However, social learning does not guarantee accurate learning or better decisions: Other people's knowledge can be as limited as our own, and their advice is not always helpful. This study examines how human learners put two “imperfect” heads together to make utility‐maximizing decisions. Participants played a card game where they chose to “stay” with a card of known value or “switch” to an unknown card, given an advisor's advice to stay or switch. Participants used advice strategically based on which cards the advisor could see (Experiment 1), how helpful the advisor was (Experiment 2), and what strategy the advisor used to select advice (Experiment 3). Overall, participants benefited even from imperfect advice based on incomplete information. Participants’ responses were consistent with a Bayesian model that jointly infers how the advisor selects advice and the value of the advisor's card, compared to an alternative model that weights advice based on the advisor's accuracy. By reasoning about others’ minds, human learners can make the best of even noisy, impoverished social information. 相似文献
Breast cancer vaccines composed of antigens identified by serological analysis of cDNA expression libraries (SEREX) induce antigen specific immune responses in patients but have had disappointing clinical benefits. While many attempts to modify the adjuvants and vaccine method have been tried, one issue not addressed was whether the SEREX tumor-associated antigens identified from late stages of disease were ideal targets. We questioned in the transgenic TgMMTV-neu mouse model whether the antigen repertoire is distinct between early and late stage breast cancer and whether the antigens identified via SEREX from transgenic mice with early or late stage tumors would elicit differential anti-tumor effects to address this question.Three early stage antigens, Pdhx, Stk39, and Otud6B, were identified from a SEREX screen of mice prior to development of palpable lesions. Formulated into a vaccine, each early antigen inhibited tumor growth (p < 0.0001). The antigens identified from mice with late stage tumors (Swap70, Gsn, and Arhgef2) were unable to inhibit tumor growth when used as vaccines (for example Gsn p = 0.26). Each of the three early stage antigens were essential for tumor survival in syngeneic mouse tumor cells and in human breast cancer cell lines across breast cancer subtypes. Silencing protein expression of the early antigens increased apoptosis (p < 0.0001 for all antigens in mouse and p < 0.05 for all antigens in human triple negative breast cancer) and decreased survival (p < 0.0001 for all antigens in mouse and human triple negative and HER2 positive breast cancer). Overexpression of the early stage antigens in women with breast cancer predicted worse prognosis (p = 0.03) while overexpression of late stage antigens did not impact prognosis (p = 0.09). These data suggest that antigens expressed earlier in breast tumor development and functionally relevant to breast tumor growth may be more effective targets for therapeutic breast cancer vaccines than antigens identified in later disease. 相似文献
Introduction: There are at the minimum two major, quite different approaches to advance drug discovery. The first being the target-based drug discovery (TBDD) approach that is commonly referred to as the molecular approach. The second approach is the phenotype-based drug discovery (PBDD), also known as physiology-based drug discovery or empirical approach.
Area covered: The authors discuss, herein, the need for developing radiation countermeasure agents for various sub-syndromes of acute radiation syndromes (ARS) following TBDD and PBDD approaches. With time and continuous advances in radiation countermeasure drug development research, the expectation is to have multiple radiation countermeasure agents for each sub-syndrome made available to radiation exposed victims.
Expert opinion: The majority of the countermeasures currently being developed for ARS employ the PBDD approach, while the TBDD approach is clearly under-utilized. In the future, an improved drug development strategy might be a ‘hybrid’ strategy that is more reliant on TBDD for the initial drug discovery via large-scale screening of potential candidate agents, while utilizing PBDD for secondary screening of those candidates, followed by tertiary analytics phase in order to pinpoint efficacious candidates that target the specific sub-syndromes of ARS. 相似文献
The modular binding sites on the influenza A(H3N2) hemagglutinin protein are under significant pressure to acquire mutations in order to evade human antibody recognition. Analysis of these hemagglutinin epitopes in the strains circulating during 2017/18 and early 2018/19 identified the emergence of a new antigenic cluster that has grown from 4% of circulating strains to 11%. We regressed our module-based antigenic distance, pepitope, with A(H3N2) vaccine effectiveness from recent studies conducted by the US Centers for Disease Control and Prevention (r2 = 0.92), and we used this to estimate that the 2018/19 vaccines will protect against most circulating A(H3N2) strains. The pEpitope model is useful for A(H3N2) influenza vaccine virus selection and development, and it has the potential to aid national or regional regulatory authorities in making geographically localized decisions. 相似文献