This study determined the muscle effort and fatigue of the upper extremity while performing fundamental surgical skills training tasks. Ten novices performed three tasks (precision cutting, needle passing, and peg transfer) using either a virtual simulator or a laparoscopic box-trainer. Their electromyography (EMG) activities in both proximal and distal parts of upper extremity were measured. Significantly more muscle effort were required to complete tasks with the box-trainer, whereas similar muscle fatigue levels between tasks were found in both training environments. These EMG results demonstrated how the virtual trainer could provide meaningful physiological value to the surgeon training in laparoscopic surgery.

关键词：虚拟现实;培养箱;肌电图;上肢;外科训练

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Disorders of gastrointestinal motility are common, resulting in a decreased quality of life of individuals, and an economic burden. Gastrointestinal motility is categorized according to location within the gastrointestinal tract: stomach, small intestine, and colon, with the colon being the dominant compartment in determining overall gastrointestinal transit. Constipation results from gastrointestinal dysmotility and is a significant chronic health issue globally. Clinical studies in a range of adult populations consistently indicate that kiwifruit are a highly effective dietary option to promote laxation.This, together with emerging evidence for the putative effects of kiwifruit in beneficially promoting gastric emptying and digesta mixing, suggests that kiwifruit are physiologically active throughout the gastrointestinal tract. Although the mechanisms of this action remain unknown, the unique behavior of kiwifruit fiber during digestion and the potential action of bioactive components in kiwifruit may contribute to the effectiveness of kiwifruit in modulating gastrointestinal motility.

关键词：肠胃蠕动；结肠；调节；慢性疾病

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Work done during the first year of the award resulted in the identification and characterization of a set of 29 A. baumannii strains isolated from wounded military personnel with regard to their capacity to grow under iron-limiting conditions, produce iron chelators siderophores and form biofilms on abiotic surfaces found in medical settings. This analysis indicates that all isolates form biofilms on abiotic surfaces and different strains produce and/or use different siderophores when cultured under iron chelation. However, all tested strains produce dihydroxybenzoic acid derivatives, the synthesis of which could be used as a therapeutic target. Accordingly, salicylic acid derivatives seem to inhibit bacterial growth under iron chelation. Equally encouraging is the observation that gallium-containing derivatives, particularly Gaprotoporphyrin IX, inhibit bacterial growth independently of the iron and nutrient content of the medium. These are encouraging observations that will be tested in animal models proposed in this project and promote future basic studies since the mechanisms by which Ga-PPIX inhibit A. baumannii growth are unknown. Work done during this first year together with preliminary data collected by collaborators also resulted in the selection of the AB5075 isolate as a model strain for more extensive studies. This clinical isolate proved to be virulent when tested using ex vivo and in vivo experimental infection models and amenable to genetic manipulations, including high throughput insertion mutagenesis and genetic complementation with shuttle cloning vectors under construction.

关键词：细菌性疾病,革兰氏阴性细菌;传染病;细菌;化学衍生品;临床医学;协作技术;补充(生物学);基因工程

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Project 1. We will determine the early molecular changes in STIC and their biological significance in developing high-grade serous carcinoma. marker selection and sample preparation will begin in the next coming months. Project 2. We will evaluate whether the presence of a STIC is associated with different clinical manifestations and/or outcome compare to those patients in whom a STIC was not identified. Molecular profiling will be initiated after quality control checking. Project 3. We will identify the early molecular changes that precede the development of STICs using gene expression analysis of morphologically normal FTE from high-risk women compared to FTE from normal control specimens and use an in vitro system and a mouse model to generate a molecularly defined carcinoma resembling HGSC from FTE and OSE using oncogenes expressed in ovarian carcinoma. Project 4 We plan to if the statin drugs are effective in preventing STIC formation and suppress tumor progression in the OVGP1 mouse model that spontaneously develops STIC and neoplasms.. Project 5. With the data and cases piling up, we will be able to address the molecular and epidemiologic profile of putative precursor lesions including STIC in the fallopian tubes and ovaries from women at high-risk for ovarian cancer. Also, a pilot study will be performed to determine the most cost-effective way to prepare the tissue sections for studies related to study early tumor development in ovarian cancer. This information will be shared with science community.

关键词：解剖模型;生物学;癌;临床医学;控制;药物;流行病学;基因;体外分析;损伤;标志;分子;肿瘤;癌病毒;卵巢癌;卵巢;患者;试验研究;前兆;制备;预防;生殖系统

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Early prediction of the adverse outcomes associated with heat stress is critical for effective management and mitigation of injury, which may sometimes lead to extreme undesirable clinical conditions, such as multiorgan dysfunction syndrome and death. Here, we developed a computational model to predict the spatiotemporal temperature distribution in a rat exposed to heat stress in an attempt to understand the correlation between heat load and differential organ dysfunction. The model includes a three-dimensional representation of the rat anatomy obtained from medical imaging and incorporates the key mechanisms of heat transfer during thermoregulation. We formulated a novel approach to estimate blood temperature by accounting for blood mixing from the different organs and to estimate the effects of the circadian rhythm in body temperature by considering day-night variations in metabolic heat generation and blood perfusion. We validated the model using in vivo core temperature measurements in control and heat-stressed rats and other published experimental data. The model predictions were within 1 SD of the measured data. The liver demonstrated the greatest susceptibility to heat stress, with the maximum temperature reaching 2 C higher than the measured core temperature and 95% of its volume exceeding the targeted experimental core temperature. Other organs also attained temperatures greater than the core temperature, illustrating the need to monitor multiple organs during heat stress. The model facilitates the identification of organspecific risks during heat stress and has the potential to aid in the development of improved clinical strategies for thermal-injury prevention and management.

关键词：血;体温;临床医学;障碍;接触(通用);热应力(生理学);传热;医疗服务;代谢;器官(解剖)

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Circulating tumor cells (CTC) mediate metastatic spread of many solid tumors. Our proposal exploited a new technology, MagSweeper, for isolation of CTCs from patients with prostate cancer. MagSweeper is an automated immunomagnetic separation technology that gently extracts CTCs from whole blood, allowing the possibility of characterization of the cells molecularly. We have now successfully demonstrated that the MagSweeper isolates completely purified CTCs while preserving the integrity and viability of these fragile cells and eliminating contamination from nonspecific adsorption or entrapment of blood cells. We have optimized the isolation of spiked LNCaP cells from the blood of healthy donors and then from the isolated cells performed whole transcriptome mRNA-Seq. MagSweeper can effectively isolate these cells with a high capture efficiency and purity. In addition, the MagSweeper isolation process does not significantly perturb the transcriptional signature of isolated single cells. We also have been able to isolate CTCs from patients with metastatic prostate cancer, and the numbers of cells isolated were comparable to CellSearch, a commercial FDA approved CTC counting technology. Although the quality of RNA from the CTCs has showed signs of degradation, we have been able to generate whole transcriptome profiles from single cells from patients using mRNA-Seq. Expressed transcripts showed the cells were of prostatic origin and reflected known aspects of prostate cancer biology. These results demonstrate that the MagSweeper provides access to intact CTCs and that it is possible to extract biologically and clinically relevant information from molecular analysis of single CTCs.

关键词：血液细胞,血液循环,捐助者(医学);红细胞;转移;前列腺癌;症状和体征

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The purpose of this study is to determine the functional role of the putative oncogene BORIS in ovarian cancer. The proposed studies will use a newly developed mouse model system to assess the oncogenic potential of BORIS expression in the ovarian surface epithelium, alone and in combination with Rb and p53 knockout. In the past year we have accomplished a number of objectives: (i) we have obtained IACUC and Biosafety approvals for the proposed studies, (ii) we designed and constructed a new conditional overexpression construct (iZEG- CTCFL) to drive BORIS expression in mice, (iii) we have designed a TALEN approach to target iZEG-CTCFL to the ROSA26 locus in mice. The constructs have been injected into fertilized eggs from FVB/N mice, and we are currently awaiting founder mice. (iv) we have obtained double conditional knockout mice (Rb, p53) in FVB/N background and bred with FVB/N wild-type mice, obtained F1 and intercrossed to generate stocks of single Rbflox or p53flox mice, (v) Ms. Joanna March, the Teal scholar, has learned how to carry out intrabursal injections and has begun these experiments to meet the study objectives, and (vi) Ms. March has learned how to isolate and culture OSE cells from mice and has begun to isolate and utilize these cultures to meet the study objectives.

关键词：解剖模型;文化;生育;体内分析;注射,注射(医学);模型;致瘤的病毒;卵巢癌;蛋白质

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At least one in four of the nearly 700,000 U.S. veterans of the 1990- 1991 Gulf War are affected by Gulf War illness (GWI), the chronic condition currently defined only by veterans self-reported symptoms. Previous studies have identified neurological, inflammatory, endocrine, and hematological measures that significantly distinguish groups of GWI cases from controls. Using state-of-the-art biodiscovery techniques, the present study is designed to identify a biological signature for GWI that can be used clinically as a diagnostic blood test. A multiphase case-control design is used to canvas a broad spectrum of blood analytes in three independent samples of Gulf War veterans. The multiplex assay platform includes a diverse array of cytokines, chemokines, growth factors, hormones, hematological measures, and neurotrophic factors, and provides highly replicable and accurate quantitative values for each analyte. The pattern of analytes whose values most reliably distinguish veterans with GWI from healthy controls in the first two development samples will be assembled, and tested in the third validation sample, to determine the test s sensitivity and specificity for diagnosing GWI and/or identified GWI subgroups. If successful, the availability of an objective test for diagnosing GWI will be immensely beneficial to veterans and their healthcare providers, and provide an important tool for improving research to better understand and treat GWI.

关键词：血;诊断(医学);对立;疾病;战争退伍军人

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Following treatment with chemotherapeutic agents, responsive ovarian cancer cells undergo apoptotic cell death. Several groups have shown that the apoptotic protease, caspase 2 (C2), is an essential activator of cell death in ovarian cancer cells treated with cisplatin and we have found, by knock-down of C2 in ovarian cancer cells, that C2 is also required for responsiveness to microtubule perturbing agents such as paclitaxel. Work from our laboratory has demonstrated that C2 is normally controlled by the metabolic status of the cell in that high levels of flux through the pentose phosphate pathway (PPP) prevents activation of C2 . This inhibition is exerted through phosphorylation of C2 at a specific residue that is catalyzed by calcium-calmodulin-dependent kinase II (CaMKII). CaMKII is activated by the product of the PPP, NADPH, through its ability to support fatty acid synthesis. The precise mechanism by which fatty acid synthesis activates CaMKII is not yet known. Because ovarian cancers exhibit increased glucose uptake and increased fatty acid synthesis, we hypothesized that susceptibility of ovarian cancers to front-line chemotherapeutic agents, reflect, at least in part, the metabolic status of the cells and, consequently, the phosphorylation state of caspase 2. We have found that inhibition of PPP operation and interference with fatty acid synthesis sensitizes ovarian cancer cells to a range of chemotherapeutic agents that depend upon C2 for cell death.

关键词：半胱天冬酶2;细胞(生物学);化疗药物;化疗;死亡;脂肪酸合成;脂肪酸;葡萄糖;代谢;卵巢癌;肽水解酶;扰动;磷酸化

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The metabolic consequences of obesity may be critical in the development of ovarian cancer (OC), resulting in biologically different cancers than those that arise in leaner women. This may occur through aberrant modulation of mTOR signaling, given that alterations in this pathway are common in both obesity and OC. Thus, obese OC patients may derive increased benefit from chemotherapeutic agents related to inhibition of this pathway, such as mTOR inhibitors (everolimus) or metformin. We have demonstrated that the obese state can promote tumor progression in the KpB mouse model of OC. The ovarian tumors that arose in the obese mice were genomically and metabolically different from those that arose in non-obese mice. Metformin was found to be more efficacious in the obese versus non-obese KpB mice, suggesting that obesity may be a biomarker for response to this agent. For our in vitro studies, metformin and everolimus were found to be more effective in the inhibition of proliferation and induction of apoptosis under low versus high glucose concentrations. We postulate that OC cells deprived of glucose have blunted proliferative capacity, rendering them more susceptible to metformin and everolimus, and that a high glucose environment may overall enhance proliferative capacity.

关键词：异常;解剖模型;化疗药物,临床医学;浓度(化学);浓度(作文);环境;基因;葡萄糖;影响;体外分析;感应系统;抑制;抑制剂;代谢;调制;肿瘤;肥胖;卵巢癌;卵巢;病理;患者;反应;信号

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