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1.
New treatment strategies are urgently needed to overcome early mortality in acute bacterial infections. Previous studies have shown that administration of a novel immunoactivating peptide (P4) alongside passive immunotherapy prevents the onset of septicemia and rescues mice from lethal invasive disease models of pneumococcal pneumonia and sepsis. In this study, using two diverse populations of adult volunteers, we determined whether P4 treatment of human alveolar macrophages would upregulate phagocytic killing of Streptococcus pneumoniae ex vivo. We also measured macrophage intracellular oxidation, cytokine secretion, and surface marker expression following stimulation. Peptide treatment showed enhanced bacterial killing in the absence of nonspecific inflammation, consistent with therapeutic potential. This is the first demonstration of P4 efficacy on ex vivo-derived human lung cells.  相似文献   
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Direct cytotoxic effects of radiocontrast (RC) agents have been implicated in radiocontrast nephropathy (RCIN). The interaction between extracellular calcium, which plays a central role in intercellular contacts, and the in vitro toxicity of RC was tested in Madin-Darby canine kidney (MDCK) cell monolayers grown on permeable supports. Cell viability was determined by trypan blue exclusion. The function of intercellular junctions was assessed by measuring the electrical transmonolayer resistance (TMR). The cell contacts were examined with indirect immunofluorescence microscopy using antibodies against the junctional proteins E-cadherin, ZO-1 and occludin. The ionic RC agents diatrizoate and ioxaglate (74 mg iodine/ml), but not the nonionic compounds iohexol or iodixanol, decreased ionized calcium (Ca2+) in the incubation media from 1.48 +/- 0.04 mM (control) to 0.89 +/- 0.06 mM (diatrizoate), respectively to 1.05 +/- 0.08 mM (ioxaglate). Diatrizoate, and to a lesser extent ioxaglate, reduced the number of viable MDCK cells and showed a redistribution of the E-cadherin, ZO-1 and occludin immunofluorescence signal with a parallel decrease of the TMR indicating an impaired monolayer integrity. A similar reduction of extracellular Ca2+ through EGTA failed to reproduce these effects. Conversely, raising Ca2+ in diatrizoate-containing media to control levels did not abrogate its toxicity. In conclusion, the ionic RC agents diatrizoate and ioxaglate, but not the nonionic compounds iohexol or iodixanol, reduce extracellular Ca2+ in vitro. However, this reduction of Ca2+ does not explain their cytotoxic effects which could contribute to the pathogenesis of RCIN in vivo by opening intercellular junctions.  相似文献   
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We investigated the hypothesis that increased prefrontal activations in older adults are compensatory for decreases in medial-temporal activations that occur with age. Because scene encoding engages both hippocampal and prefrontal sites, we examined incidental encoding of scenes by 14 young and 13 older adults in a subsequent memory paradigm using functional magnetic resonance imaging (fMRI). Behavioral results indicated that there were equivalent numbers of remembered and forgotten items, which did not vary as a function of age. In an fMRI analysis subtracting forgotten items from remembered items, younger and older adults both activated inferior frontal and lateral occipital regions bilaterally; however, older adults showed less activation than young adults in the left and right parahippocampus and more activation than young adults in the middle frontal cortex. Moreover, correlations between inferior frontal and parahippocampal activity were significantly negative for old but not young, suggesting that those older adults who showed the least engagement of the parahippocampus activated inferior frontal areas the most. Because the analyses included only the unique activations associated with remembered items, these data suggest that prefrontal regions could serve a compensatory role for declines in medial-temporal activations with age.  相似文献   
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BACKGROUND: Diffuse and cystic epithelial downgrowth occur rarely, but they represent a mostly preventable potential cause of blindness as sequels to trauma and surgery. The aim of this study is to report on the etiology and course of disease in patients with histologically verified epithelial downgrowth. PATIENTS AND METHODS: From 1986 until 2000 the ophthalmopathological laboratory of the University Eye Hospital Hamburg-Eppendorf received 13 (4 external) referrals. Ten patients with cystic of diffuse intraocular epithelial downgrowth were treated and 9 eyes were operated on in the Hospital. RESULTS: At presentation 4/10 patients had a visual acuity of < or = 0.1, and 2/10 had no light perception. A cystic epithelial downgrowth was verified histologically in 9/13, and a diffuse form in 4/13 patients. Mucin production was proven histochemically in 1/9 intraocular epithelial downgrowth sections. In one case a spontaneous iris cyst was detected by the immunohistological examinations. Trauma (10/14) and surgery (3/14) were the most frequent causes and were symptomatic on average 17 years after the primary event. A curative surgery was done in 13/14 patients (5 x en bloc excision, 2 x penetrating keratoplasty, 1 x iridectomy, 2 x enucleations, 3 x external) resulting in no recurrences during the follow-up of 4(1/2) years (1 - 12 years). The postoperative visual acuity was ameliorated in 5/9, worsened in 2 patients, and 2 were enucleated. CONCLUSIONS: Epithelial downgrowth is a rare but preventable cause of blindness. The most important prophylaxis is meticulous primary surgery including a sufficient wound closure. The visual outcome depends on the preoperative conditions.  相似文献   
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BACKGROUND: The purpose of the study was to ascertain those learning objectives that will initiate increased use of telemedicine by military health care providers. Telemedicine is increasingly moving to the center of the health care industry's service offerings. As this migration occurs, health professionals will require training for proper and effective change management. The United States Department of Defense (DoD) is embracing the use of telemedicine and wishes to use Web-based training as a tool for effective change management to increase use. This article summarizes the findings of an educational needs assessment of military health care providers for the creation of the DoD Web-based telemedicine training curriculum. METHODS: Forty-eight health care professionals were interviewed and surveyed to capture their opinions on what learning objectives a telemedicine training curriculum should include. RESULTS: Twenty learning objectives were found to be needed in a telemedicine training program. These 20 learning objectives were grouped into four learning clusters that formed the structure for the training program. In order of importance, the learning clusters were clinical, technical, organizational, and introduction to telemedicine. FINDINGS: From these clusters, five Web-based modules were created, with two addressing clinical learning needs and one for each of the other learning objective clusters.  相似文献   
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This case study describes how the Evolve electronic course management system was used to deliver an online Trends and Issues in Nursing course for 53 nurses-in-training at Our Lady of Lourdes School of Nursing. Evolve provided an open-ended, electronic course shell that supported the instructor's efforts to create an online learning environment using the seven principles of effective teaching. The course was evaluated with items from the Student Evaluation of Online Teaching Effectiveness and questions written to assess unique features of the Trends and Issues course. Results indicated that most learners perceived that the course was generally a positive learning experience and that constructivist-based principles were used to design and deliver instruction that effectively promoted student learning.  相似文献   
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Abstract: Pigmented vulvar lesions were observed In a child during a sexual abuse evaluation. Gross examination of the lesions appeared most consistent with bowenoid papulosis; however, biopsy confirmed the le-sions to be pigmented apocrine hamartomas. To our knowledge, these rare and benign tumors have never been described as pigmented, but should be added to the differential diagnosis of pigmented vulvar lesions.  相似文献   
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