Anterograde TNFα Transport From Rat Dorsal Root Ganglion To Spinal Cord And Injured Sciatic Nerve

Spontaneous activity originating in the injured nerve or the dorsal root ganglion (DRG) has been implicated in the development and maintenance of neuropathic pain. The inherent characteristics of spontaneous activity and the causal factors that modulate its firing pattern and frequency are not fully understood. We attempted to assess the thermosensitivity of spontaneous activity in dorsal root ganglion (DRG) neurons in normal rats and in rat, with cl-ironic compression of the DRG (CCD) in an in vitro nerve-DRG preparation. Extracellular, dorsal root recording from 66 spontaneously active CCD Abeta fibers indicate that: (1) decreasing bath temperature from 37 to 36-26 °C significantly decreased the firing rate (FR) in 85% (56/66) of fibers tested, of which 19 fibers (34%) responded to temperature change at physiological range (36-37 °C), whereas the remaining fibers responded at lower temperature levels (26-36 °C); (2) cooling of the DRG increased the FR in 12% (8/66) of fibers tested; (3) similarly, the firing rate of 21/26 spontaneously active Abeta fibers from normal rats was decreased following temperature decrease; (4) intracellular recordings from 38 normal neurons revealed that cooling the DRG significantly increased the action potential (AP) threshold, A-P duration, AP amplitude and afterhyperpolarization (AHP) duration, but decreased AHP amplitude, maximal depolarizing and repolarizing rates. There was no significant change in the rheobase currents or the resting membrane potential. The present study indicates that large sensory neurons with myelinated axons are temperature dependent. It also suggests that maintenance of a stable temperature is critical for reliable characterization of spontaneous activity of sensory neurons.     

Implementing and Evaluating a Four-Year Integrated End-of-Life Care Curriculum for Medical Students

Problem: Meeting the needs of patients with life-limiting and terminal illness requires effectively trained physicians in all specialties to provide skillful and compassionate care. Despite mandates for end-of-life (EoL) care education, graduating medical students do not consistently feel prepared to provide this care. Intervention: We have developed a longitudinal, integrated, and developmental 4-year curriculum in EoL care. The curriculum's purpose is to teach basic competencies in EoL care. A variety of teaching strategies emphasize experiential, skill-building activities with special attention to student self-reflection. In addition, we have incorporated interprofessional learning and education on the spiritual and cultural aspects of care. We created blended learning strategies combining interactive online modules with live workshops that promote flexibility, adaptability, and interprofessional learning opportunities. Context: The curriculum was implemented and evaluated in the 4-year program of studies at Yale School of Medicine. Outcome: A mixed-method evaluation of the curriculum included reviews of student written reflections and questionnaires, graduating student surveys, and demonstration of 4th-year students’ competency in palliative care with an observed structured clinical examination (OSCE). These evaluations demonstrate significant improvements in students’ self-reported preparedness in EoL care and perceptions of the adequacy in their instruction in EoL and palliative care, as well as competency in primary palliative care in a newly developed OSCE. Lessons Learned: A 4-year longitudinal integrated curriculum enhances students’ skills and preparedness in important aspects of EoL care. As faculty resources, clinical sites, and curricular structure vary by institution, proven and adaptable educational strategies as described in this article may be useful to address the mandate to improve EoL care education. Teaching strategies and curricular components and design as just described can be adapted to other programs.     

Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study

OBJECTIVE: The objective of this Phase 3 study was to confirm the efficacy and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome), a rare, fatal lysosomal storage disease with no effective treatment. STUDY DESIGN: Thirty-nine patients with MPS VI were evaluated in a randomized, double-blind, placebo-controlled, multicenter, multinational study for 24 weeks. The primary efficacy variable was the distance walked in a 12-minute walk test (12MWT), whereas the secondary efficacy variables were the number of stairs climbed in a 3-minute stair climb (3MSC) and the level of urinary glycosaminoglycan (GAG) excretion. All patients received drug in an open-label extension period for an additional 24 weeks. RESULTS: After 24 weeks, patients receiving rhASB walked on average 92 meters (m) more in the 12MWT (p=.025) and 5.7 stairs per minute more 3MSC (p=.053) than patients receiving placebo. Continued improvement was observed during the extension study. Urinary GAG declined by -227+/-18 microg/mg more with rhASB than placebo (p<.001). Infusions were generally safe and well tolerated. Patients exposed to drug experienced positive clinical benefit despite the presence of antibody to the protein. CONCLUSION: rhASB significantly improves endurance, reduces GAG, and has an acceptable safety profile.     

航天员训练中心模拟设备的制作和应用

本文介绍了俄罗斯航天员训练中心模拟设备设计的基本概念及应用情况。在研制和使用模拟器设备加采用了以下几条原则：分层原则，模块原则，通用原则，整合原则，文中还介绍了中性浮力水槽，离心机，综合训练模拟器，ＴＵ－１５４ＭＬＫ－１和ＩＬ－７６ＭＤＫ失重飞机等训练设备。     

Transcatheter embolization in the management of pulmonary hemorrhage

A group of 306 patients with acute pulmonary hemorrhage were evaluated by means of bronchial arteriography and treated with transcatheter embolization. Specific causes for bleeding included lung abscess, chronic pneumonia, tuberculosis, lung cancer, and bronchiectasis. In 120 patients the hemoptysis was massive, with volumes exceeding 500 ml/day. The majority (n = 225) were treated during peak hemorrhage. Embolization was performed with one of three methods: particulate embolization with polyurethane or velour, obturation with the angiographic catheter combined with peripheral embolization by means of infused albumin macroaggregates, and regional infusion of sclerosing agents. Effective hemostasis was obtained initially in 278 patients (90.8%), including 87.5% of those treated during peak hemorrhage. In 26 of 28 cases without initial response, the pulmonary artery was the source of bleeding. Recurrent bleeding, within 1-4 days, requiring surgery was observed in 39 patients with initially successful hemostasis. Of 158 patients who were treated without surgery, subsequent episodes of hemoptysis occurred in 36. Combined methods of embolization may improve the efficacy of treatment of operable and inoperable patients with lung disease complicated by hemorrhage.