Synaptic pathology, altered gene expression, and degeneration in photoreceptors impacted by drusen.

PURPOSE: Drusen are risk factors for age-related macular degeneration and have been shown to negatively impact cells of the RPE and retina. In this study, the effects of drusen on the synaptic machinery of retinal photoreceptors are investigated. METHODS: Human donor eye tissue containing retina, RPE, and choroid was processed for confocal immunofluorescence microscopy, laser capture microdissection, and light and electron microscopy. Tissue sections were immunostained with a panel of antibodies to synapse-associated proteins. Populations of photoreceptors over drusen and normal populations of photoreceptors were microdissected from fresh frozen tissue, RNA was purified, and quantitative PCR was performed to compare relative levels of gene expression. RESULTS: The number of photoreceptor synaptic terminals is reduced in regions of the outer plexiform layer over drusen, synaptic proteins are mislocalized in photoreceptor cells, and synaptic terminals are often observed within the outer nuclear layer. Photoreceptors over drusen also increase expression of the stress response proteins apolipoprotein E and alphaB-crystallin. Abnormal immunolabeling patterns are not restricted to photoreceptors directly over drusen but are also observed in cells flanking drusen. Gene expression analysis confirms reductions in the expression of genes coding for synapse-associated proteins and signal transduction proteins and increases in the expression of apolipoprotein E and alphaB-crystallingene transcripts. Ultrastructural analysis of photoreceptor synaptic terminals over drusen reveals significant abnormalities, and cell counts show a reduction in photoreceptor density directly over, and lateral to, drusen of all sizes. CONCLUSIONS: Photoreceptors overlying and flanking drusen exhibit morphologic and biochemical signs of degeneration. The expression of synapse-associated proteins decreases in photoreceptor synaptic terminals, whereas the expression of stress-response proteins increases. Reductions in photoreceptor cell densities over, and flanking, drusen suggest that these degenerative effects eventually result in the death of photoreceptors.

Comparison between emergency department and inpatient nurses' perceptions of boarding of admitted patients.

INTRODUCTION: The boarding of admitted patients in the emergency department (ED) is a major cause of crowding and access block. One solution is boarding admitted patients in inpatient ward (W) hallways. This study queried and compared ED and W nurses' opinions toward ED and W boarding. It also assessed their preferred boarding location if they were patients. METHODS: A survey administered to a convenience sample of ED and W nurses was performed in a 631-bed academic medical center (30,000 admissions/year) with a 68-bed ED (70,000 visits/ year). We identified nurses as ED or W, and if W, whether they had previously worked in the ED. The nurses were asked if there were any circumstances where admitted patients should be boarded in ED or W hallways. They were also asked their preferred location if they were admitted as a patient. Six clinical scenarios were then presented, and the nurses' opinions on boarding based on each scenario were queried. RESULTS: Ninety nurses completed the survey, with a response rate of 60%; 35 (39%) were current ED nurses (cED), 40 (44%) had previously worked in the ED (pED). For all nurses surveyed 46 (52%) believed admitted patients should board in the ED. Overall, 52 (58%) were opposed to W boarding, with 20% of cED versus 83% of current W (cW) nurses (P < 0.0001), and 28% of pED versus 85% of nurses never having worked in the ED (nED) were opposed (P < 0.001). If admitted as patients themselves, 43 (54%) of all nurses preferred W boarding, with 82% of cED versus 33% of cW nurses (P < 0.0001) and 74% of pED versus 34% nED nurses (P = 0.0007). The most commonly cited reasons for opposition to hallway boarding were lack of monitoring and patient privacy. For the 6 clinical scenarios, significant differences in opinion regarding W boarding existed in all but 2 cases: a patient with stable chronic obstructive pulmonary disease but requiring oxygen, and an intubated, unstable sepsis patient. CONCLUSION: Inpatient nurses and those who have never worked in the ED are more opposed to inpatient boarding than ED nurses and nurses who have worked previously in the ED. Primary nursing concerns about boarding are lack of monitoring and privacy in hallway beds. Nurses admitted as patients seemed to prefer not being boarded where they work. ED and inpatient nurses seemed to agree that unstable or potentially unstable patients should remain in the ED but disagreed on where more stable patients should board.