Conserved gene order at the nuclear periphery in Drosophila.

Whether higher-order chromatin organization is related to genome stability over evolutionary time remains elusive. We find that regions of conserved gene order across the genus Drosophila are larger if they harbor genes bound by B-type lamin (Lam) and Suppressor of Under-Replication (SUUR), two proteins located at the nuclear periphery. Low recombination rates and coexpression of genes in regions of conserved gene order do not explain the lower probability of disruption in these regions by genome rearrangements. Instead, we find a significant colocalization between evolutionarily stable genomic regions associated with Lam and sequences thought to regulate local gene expression, which have the potential to impose constraints on genome rearrangement. At least in the genus Drosophila, localization of particular genomic regions at the nuclear periphery is intimately associated with their long-term integrity during evolution.

Effect of antenatal betamethasone on blood glucose levels in women with and without diabetes.

OBJECTIVE: To characterize the maternal glycemic response to betamethasone in subjects without diabetes compared to subjects with diabetes. STUDY DESIGN: Blood glucose levels in 22 gravidae without diabetes and 11 gravidae with diabetes were recorded for 48h following betamethasone administration for threatened preterm delivery. Maximum blood glucose value and time to maximum value were compared. Area under the curve calculations were used to express the duration and degree of significant hyperglycemia for individual subjects. These summary measures were then correlated to subject characteristics and laboratory values to determine a risk profile of those subjects without diabetes at risk for significant hyperglycemia. RESULTS: All subjects with diabetes and the majority of those without diabetes had significant hyperglycemia during the study period. Mean maximum blood glucose was higher for those with diabetes (205mg/dL vs. 173mg/dL, p⩽0.01). Mean time to reach the maximum glucose level was similar for both groups. Result of a glucose tolerance test given immediately prior to betamethasone correlated strongly with amount of time spent with hyperglycemia for subjects without diabetes (rho=0.59, p⩽0.01). Morbidly obese subjects spent less time with hyperglycemia than those with lower body mass indices (p=0.03). CONCLUSION: Both subjects with and without diabetes demonstrate significant hyperglycemia after receipt of antenatal betamethasone.

Histopathologic characteristics of atherosclerotic coronary disease and implications of the findings for the invasive and noninvasive detection of vulnerable plaques.

OBJECTIVES: The goal of this study was to identify histomorphologic characteristics of atherosclerotic plaques and to determine the amenability of some of these components to be used as markers for invasive and noninvasive imaging. BACKGROUND: Rupture of the atherosclerotic plaques is responsible for the majority of acute coronary events, and the culprit lesions demonstrate distinct histopathologic features. It has been tacitly believed that plaque rupture (PR) is associated with angiographically minimally occlusive lesions. METHODS: We obtained 295 coronary atherosclerotic plaques, including stable (fibroatheroma [FA]; n = 105), vulnerable (thin-cap fibroatheroma [TCFA]; n = 88), and disrupted plaques (plaque rupture [PR]; n = 102) from the hearts of 181 men and 32 women who had died suddenly. The hierarchical importance of fibrous cap thickness, percent luminal stenosis, macrophage area, necrotic core area, and calcified plaque area was evaluated by using recursive partitioning analysis. Because clinical assessment of fibrous cap thickness is not possible by noninvasive imaging, it was excluded from the second set of partitioning analysis. RESULTS: Thickness of the fibrous cap emerged as the best discriminator of plaque type; the cap thickness measured <55 µm in ruptured plaques, and all FA were associated with >84-µm cap thickness. Although the majority of TCFA were found in the 54- to 84-µm thickness group, those with <54-µm thickness were more likely to show <74% luminal stenosis (area under the curve: FA, 1.0; TCFA, 0.89; PR, 0.90). After exclusion of cap thickness, analysis of the plaque characteristics revealed macrophage infiltration and necrotic core to be the 2 best discriminators of plaque types (area under the curve: FA, 0.82; TCFA, 0.58; PR, 0.72). More than 75% cross-section area stenosis was seen in 70% of PR and 40% of TCFA; only 5% PR and 10% TCFA were <50% narrowed. CONCLUSIONS: This postmortem study defines histomorphologic characteristics of vulnerable plaques, which may help develop imaging strategies for identification of such plaques in patients at a high risk of sustaining acute coronary events.

Differences in editorial board reviewer behavior based on gender.

BACKGROUND: Reports indicate that there are gender-based differences in aspects of the peer-review process. METHODS: This is an analysis of editorial board members' reviews of original research submissions based on gender using the web-based management program, Editorial Manager, from January 1, 2002, through December 31, 2008. We evaluated recommendations of editorial board members for acceptance/rejection using a four-tier system, agreement with editor's final decision, turnaround time from review request to submission, and editors' grades of reviews on a 5-point scale. We evaluated the performance of editorial board members with advancing tenure, seeking trends in recommendations over time. RESULTS: We included 6062 manuscript reviews representing 5958 manuscripts; 67% were assigned to male editorial board members and 33% to females. There were 38 editorial board members (25 men, 13 women) with tenure duration from 2 to 4.9 years, and 3 editors (2 men, 1 woman) serving 7, 7, and 6 years, respectively. Women were less likely to accept or accept with minor revisions than men (p < 0.003). Median turnaround times were 14 (0-55) days for women and 10 (0-33) days for men (p < 0.001). The editors' grades assigned to women were more often than men's grades in the very good to exceptional category (p < 0.0001). There was no difference based on gender, with approximately 73% decision congruence overall with the editors' final decisions. Men rejected more manuscripts than did women with advancing tenure on the editorial board (p < 0.0001). CONCLUSIONS: There are differences based on gender of editorial board members' recommendations about manuscript triage, turnaround time, and editors' grades assigned. Overall, however, these differences do not affect editors' ultimate decisions about manuscript publication.