Posttraumatic osteoarthritis affects approximately 5.6 million Americans annually. Those affected are typically younger and more active than persons with primary osteoarthritis. Arthrodesis is the typical management option for persons with end-stage ankle and subtalar posttraumatic arthritis. Arthroplasty is typically reserved for elderly persons. The functional limitations resulting from any of these strategies make treatment of this young population challenging. Combat wounds frequently lead to severe lower extremity injuries. We present a series of patients with severe posttraumatic osteoarthritis of the ankle and subtalar joint after combat trauma. They were treated at our institution with an integrated orthotic and rehabilitation initiative called the Return To Run clinical pathway. This clinical pathway may serve as an alternative or adjunct to arthrodesis and arthroplasty for young patients with severe posttraumatic osteoarthritis of the ankle and subtalar joint.

关键词：医药；康复技术；骨关节炎；关节融合术；临床医学

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This study is a randomized trial of a hybrid treatment for Iraq and Afghanistan Veterans with a history of mild to moderate TBI (mTBI) and PTSD. Emotional symptoms are likely a main cause of the persistence of post- concussive symptoms while thinking problems and emotional control problems associated with mTBI can impede recovery from PTSD. However, there is no PTSD treatment specifically designed to accommodate the difficulties with attention, memory, and problem solving that patients with TBI may have. Therefore, this study integrates therapeutic approaches and tests a modification of cognitive processing therapy (CPT), an empirically supported treatment for PTSD, in which CPT is enhanced with compensatory cognitive rehabilitation principles. The enhanced CPT, called SMART-CPT is being compared to standard CPT in a group of Iraq and Afghanistan Veterans with a history of both mTBI and PTSD. Half of the participants are randomly assigned to receive standard CPT and half to receive SMART-CPT. This year was dedicated to study start up, including regulatory approvals and treatment manual development. Initial recruitment and enrollment of participants began in the final quarter of the year; six Veterans are currently enrolled and active in the protocol. There is no data to report at this time.

关键词：医药；康复技术；创伤后应激障碍；创伤性脑损伤；军事人员

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The current proposal aims to explore the relationship between brain function and connectivity in selective pathways/circuits, neuropsychological functioning, and cognitive rehabilitation response in Veterans with both Traumatic Brain Injury (TBI) and Posttraumatic Stress Disorder (PTSD). Toward this end, we propose a randomized clinical trial involving a cognitive rehabilitation intervention that targets improved executive functioning, with the participation of N=100 Veterans diagnosed with both TBI and PTSD (n=50 experimental/n=50 control). We have just begun recruitment three months ago and enrolled n=15 dyads of veterans and family members at this point.

关键词：医药；康复技术；创伤后应激障碍；退伍军人；认知康复

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This report is based on research conducted by the Minnesota Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2007-10064-I). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. The information in this report is intended to help health care decisionmakers--patients and clinicians, health system leaders, and policymakers, among othersmake well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.

关键词：医药；康复技术；脑创伤；医疗保健及竞争

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This project was focused on production of megakaryocytes and platelets from human pluripotent stem cells - originally human embryonic stem cells (hESC), but subsequently, as the technology became available, from human induced pluripotent stem cells (hiPSC). We developed a serum-free system, and also created our own cell-free extracellular matrix extracts instead of live feeder cells to support hESC and hiPSC growth and maintenance, followed by feeder cell-free cultures to create embryoid bodies, then mesenchymal cells, which then were induced to differentiate into functional megakaryocytes and platelets.

关键词：医药；人类胚胎干细胞；人类诱导多能干细胞；无血清培养

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The U.S. military is currently fitting amputees with state-of-the- art prosthetic devices. In addition to walking and changing direction on a variety of surfaces, amputees must be able to manage uneven terrain, crowded environments, stairs, ramps, and hills. The largest problem for a lower extremity amputee is falls. Among individuals with a lower extremity amputation, 52reported having fallen in the previous 12 months, 49reported being fearful of falling, and 65had low balance confidence scores. Falling history and balance confidence are associated with reduced mobility capability and social activity. As a result, lower extremity amputees with limited balance and stability are at risk for diminished quality of life. The goal of this research effort is to rehabilitate lower extremity amputees to reduce falls using a novel training method. In this first year of the research effort, we have developed a novel experimental method to induce unexpected trips to amputees under controlled laboratory conditions. We have identified objective biomechanical variables that are causally related to the success or failure in avoiding a fall after a trip, objective tests to quantify functional outcomes, and a subject-specific questionnaire to determine if the training method is effective. Enrollment has begun. Our target is to deliver a quantitatively derived, deployment-ready, advanced gait rehabilitation system that can improve functional outcomes and/or shorten the time required for injured servicemen and women to return to active duty or to a productive civilian life.

关键词：医药；康复技术；截肢；复健；军事人员

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Autonomic dysreflexia (AD), which induces excessive elevation of blood pressure, is a potentially life-threatening medical emergency that occurs in persons with spinal cord injury (SCI) at or above the mid-thoracic spinal cord segment. Since the most common source of stimulation that initiates AD is the genitourinary tract including bladder distention, followed by colorectal distension, elimination of activation of bladder sensory pathways during bladder distention could significantly reduce the incidence and/or degree of AD in SCI. Because previous studies have indicated that increased levels of nerve growth factor (NGF) in sensory pathways are one of the key factors to induce increased excitability of sensory pathways after SCI, anti-NGF therapy could be an attractive treatment of AD in SCI patients. However, systemic anti-NGF treatment such as the use of NGF antibodies reportedly induces some side effects. Therefore, we hypothesize that the local therapy of NGF antisense delivery using liposomes (LPs) in the bladder could reduce the activation of bladder sensory pathways, thereby suppressing AD during bladder distention after SCI. Using adult female rats with chronic spinal cord injury induced by Th4 spinal cord transection, we will investigate: (1) the contribution of hyperexcitable bladder sensory pathways in the emergence of AD in SCI (Aim 1), and (2) the effects of intravesical delivery of NGF antisense-liposome conjugate, which reduce NGF expression in the bladder, on AD in SCI (Aim 2). If successfully completed, this study directly addresses the feasibility of local NGF antisense treatment for SCI-induced AD and provides the foundation for future clinical translation of local NGF antisense therapy in military service members, their family members, and/or the U.S. veteran population, who suffer from autonomic dysreflexia due to SCI.

关键词：医药；治疗技术；脊髓损伤；反义治疗；军事人员

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Colorectal cancer (CRC) represents a major health burden, and is the third leading cause of cancer deaths in the U.S. In the past decade, the median survival among patients with metastatic CRC has significantly improved, primarily due the development of active chemotherapeutic regimens that include biological agents. However, despite this success, patients soon run out of therapeutic options and receive salvage therapy that results in only a few weeks of disease stability. We have proposed to employ a team science, systems biology based approach to rapidly identify novel anti-cancer agents and individualize therapeutic strategies in preclinical CRC models. In this Year 1 Progress report, we will present the tasks and key accomplishments achieved within this period of time. In brief, we have completed in vitro testing on a large panel of CRC cell lines for six novel anti-cancer agents. We have completed baseline gene expression profiling of our CRC cell lines panel and patient-derived CRC tumor explant models by high-throughput RNA sequencing approach. We have initiated the in vivo cell line derived xenograft models to test the efficacy of these novel anti-cancer agents and in the process of determining the down stream effectors of these targets by immunoblotting assays. Our research findings for RNA-seq analysis will be presented at the 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Dublin, Ireland (November 6-9, 2012). In summary, we have accomplished all the tasks that we proposed in year 1.

关键词：医药；治疗技术；结肠癌；药物化疗

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There is no difference in the rate of return to spontaneous circulation between treatment with epinephrine versus glucagon or glucagon plus epinephrine. 24 female swine 30-50kg were sedated with IV anesthesia, and instrumented (continuous aortic diastolic pressure via Millar transducer and Swan-Ganz catheter placed in pulmonary artery). Endotracheal tube was clamped. Four minutes post loss of arterial pressure, CPR was initiated via LUCAS device. We were able to create a reproducible model of asphyxia arrest. We were able to show that an active mechanical compression device (specifically LUCAS device) can provide adequate coronary perfusion pressure and there is no significant difference in CPP in relation to pig weight. We detected the ventricular fibrillation was the most common rhythm after asphyxial cardiac arrest This rhythm then degraded to asystole or bradystole.

关键词：医药；治疗技术；心血管系统；胰高血糖素；肾上腺素

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Effective treatment of sensory neuropathies in peripheral neuropathies and spinal cord injury (SCI) is one of the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord is a logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the potential of transplant of cells to treat chronic pain. Cell lines derived from the human neuronal NT2 cell line parentage, the hNT2.17 and hNT2.19 lines,which synthesize and release the neurotransmitters gamma- aminobutyric acid (GABA) and serotonin (5HT), respectively, have been used to evaluate the potential of cell-based release of antinociceptive agents near the lumbar dorsal (horn) spinal sensory cell centers to relieve neuropathic pain after PNS (partial nerve and diabetes-related injury) and CNS (spinal cord injury) damage in rat models. Both cell lines transplants potently and permanently reverse behavioral hypersensitivity without inducing tumors or other complications after grafting. Functioning as cellular minipumps for antinociception, human neuronal precursors, like these NT2-derived cell lines, would likely provide a useful adjuvant or replacement for current pharmacological treatments for neuropathic pain.

关键词：医药；治疗技术；中枢神经系统；SCI（脊髓损伤）；细胞治疗

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