Age-specific activities that support successful transition to adulthood for children with disabilities

Twenty-two activities that support transition to adulthood previously published by Blomquist et al. 1998) were explored in a focus group with parents of successful young adults with disabilities. Parents rated these activities on a 5-point Likert scale, and comments were gathered about the activities parents felt were essential for transition to adulthood. Parents rated the activities high with highest agreement being: "Do not do for them what they can do for themselves," "Assign appropriate household chores," and "Help children interact with others in varied settings." The lowest agreement ratings involved issues about school to work transitions, vocational programs within schools, and strategies assuring continuity of care with adult health care providers. Parents offered insights into the daily activities in school, home, and community that support transition to adulthood. Through review and understanding of these transition activities, health care professionals gain insight into the activities fostering a child's independence throughout their development.     

Treatment of murine Candida krusei or Candida glabrata infection with L-743,872.

L-743,872 is a broad-spectrum pneumocandin antifungal drug developed by Merck Research Co., and in the present work it was evaluated in vivo in murine models of Candida krusei and Candida glabrata infection. Mice were infected intravenously with two isolates of C. krusei and treated with fluconazole or L-743,872. Fluconazole was beneficial only in immune-competent mice infected with isolate 94-2696. At > 0.5 mg/kg of body weight/day, L-743,872 was effective against both infecting isolates in immune-competent and immune-suppressed mice. Against C. glabrata, L-743,872 was effective, at doses > or = 0.5 mg/kg, in reducing fungal cell counts in the kidneys but not in the spleen. L-743,872 has significant potential for clinical development.     

Single-Cell RNA Sequencing of Lymph Node Stromal Cells Reveals Niche-Associated Heterogeneity

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Provider-perceived barriers and facilitators for ischaemic heart disease (IHD) guideline adherence

RATIONALE, AIMS AND OBJECTIVES: Clinical practice guidelines have become a standard way of implementing evidence-based practice, yet research has shown that clinicians do not always follow guidelines. METHOD: As part of a larger study to test the effects of an intervention on provider adherence to ischaemic heart disease (IHD) guidelines, we conducted five focus groups at three Veterans Administration Medical Centers with 32 primary care providers, cardiologists, and internists to identify key barriers and facilitators to adherence of the guidelines. Using content analysis, responses were grouped into categories. RESULTS: The main perceived advantages of using the IHD guidelines were improvements in quality and the cost of care. Perceived barriers were the lack of ability of guidelines to manage the care of any one individual patient, the difficulty of accessing guidelines, and high workloads with many complex patients. While providers agreed on the benefits of aspirin, beta-blockers and angiotensin converting enzyme inhibitors, barriers for use of these medications were lack of consensus about contraindications, difficulty in providing follow-up during medication titration, and lack of patient adherence. Sources of influence for guideline use were: professional cardiology organizations, colleagues, mainly cardiologists, and key cardiology journals. However, most providers acknowledged that following guidelines was a personal practice decision. CONCLUSIONS: While results validated the influences of using clinical practice guidelines, our results highlight the importance of ascertaining guideline-specific barriers for building effective interventions to improve provider adherence. An advisory panel reviewed results and, using a modified nominal group process, chose implementation strategies targeting key barriers.     

Treatment of murine disseminated candidiasis with L-743,872.

L-743,872 (M991), which is a pneumocandin derivative, was evaluated in a mouse model of disseminated candidiasis caused by a fluconazole-resistant isolate of Candida albicans. In immunocompetent mice M991 prolonged survival at doses as low as 0.0125 mg/kg of body weight per day. In neutropenic mice 0.05 mg/kg was the lowest effective dose. M991 is a very potent drug for treatment of disseminated candidiasis.     

Guiding blind T cells and dendritic cells: A closer look at fibroblastic reticular cells found within lymph node T zones

It is within the T cell rich zone of secondary lymphoid organs (SLO) that dendritic cells (DC) present the captured pathogens to recirculating T cells in order to activate the rare antigen-specific T cells. While we have made considerable progress in understanding the biology of mobile hematopoietic cells found within SLO, notably DC and lymphocytes, we still have a lot to learn about the sessile stromal cells. This review is focused on the recent progress made in our understanding of the fibroblastic reticular stromal cells that form the 'niches' within the T zone.     

Subcellular localization of p27 and prostate cancer recurrence: automated digital microscopy analysis of tissue microarrays

Previous investigations have linked decreased nuclear expression of the cell cycle inhibitor p27 with poor outcome in prostate cancer. However, these reports are inconsistent regarding the magnitude of that association and its independence from other predictors. Moreover, cytoplasmic translocation of p27 has been proposed as a negative prognostic sign. Given the cost and accuracy limitations of manual scoring, particularly of tissue microarrays, we determined if laser-based fluorescence microscopy could provide automated analysis of p27 in both nuclear and cytoplasmic locations and, thus, clarify its significance as a prognostic biomarker. We constructed tissue microarrays covering 202 recurrent cases (rising prostate-specific antigen) and 202 matched controls without recurrence. Quadruplicate tumor samples encompassed 5 slides and 1616 cancer histospots. Cases and controls matched on age, Gleason grade, stage, and hospital. We immunolabeled epithelial cytoplasm with Alexafluor 647, p27 with Alexafluor 488, and nuclei with 4c6-diamidino-2-phenylindole·2HCl. Slides were scanned on an iCys laser scanning cytometer (CompuCyte Corp, Cambridge, MA). Nuclear crowding required a stereological approach--random arrays of circles (phantoms) were layered on images and the content of each phantom was analyzed in scatter plots. Both nuclear and cytoplasmic p27 were significantly lower in cases versus controls (P = .014 and P = .004, respectively). Regression models controlling for matching variables plus prostate-specific antigen showed strong linear trends for increased risk of recurrence with lower p27 in both nucleus and cytoplasm (highest versus lowest quartile; odds ratio, 0.35; P = .006). Manual scoring identified an inverse association between p27 expression and tumor grade but no independent association with recurrence. In conclusion, we developed an automated method for subcellular scoring of p27 without the need to segment individual cells. Our method identified a strong relationship, independent of tumor grade, stage, and prostate-specific antigen, between p27 expression--regardless of subcellular location--and prostate cancer recurrence. This relationship was not observed with manual scoring.     

Anthracycline-induced phospholipase A<Subscript>2</Subscript> inhibition

The purpose of this essay is to overview our findings that membrane-associated calcium-independent phospholipase A₂ is markedly inhibited by low, clinically relevant concentrations of anthracyclines. Our studies suggest that due to the essential role of this enzyme in membrane homeostasis, its inhibition can be one of the early culprits leading to anthracycline-induced cardiac dysfunction. The clinical importance and potential pharmaceutical use of this new phenomenon await further studies.