The impact of cesarean section on neonatal outcome of infants born at 23 weeks of gestation

Objective

Determine the impact of cesarean section (CS) on neonatal outcome of infants born at 23 weeks of gestation.

Methods

A retrospective study was performed involving 34 infants born at 23 weeks and 91 infants born at 24–26 weeks. Indications necessitating delivery were severe pregnancy induced hypertension, non-reassuring fetal heart rate patterns (NRFHRs), or intrauterine infection (IUI). Obstetrical indication for CS included NRFHR and breech presentation. Poor outcome included neonatal death or cerebral palsy. Univariate and multiple logistic analyses were performed to determine the effect of CS for obstetrical indications on poor outcome.

Results

The incidence of poor outcome was significantly higher at 23 weeks (number of poor outcomes/total number: 22/34) compared to that (31/91) at 24–26 weeks (p < 0.01). The incidence of a poor outcome was significantly higher at 23 weeks for infants having NRFHR (11/16) compared to those at 24–26 weeks (15/43, p = 0.02). However, the incidence of a poor outcome was similar in infants with IUI (6/10 at 23 weeks versus 5/11 at 24–26 weeks, p = 0.41). Vaginal birth in cases of obstetrical indication for CS at 23 weeks was associated with higher risk of a poor outcome (odds ratio: 8.2). In contrast, the risk at 24–26 weeks was not higher (OR, 0.8). After adjustment using variables of vaginal birth and IUI, vaginal birth significantly affected poor outcome (OR, 13.0).

Conclusion

Poor neonatal outcome was closely related to the mode of delivery, suggesting that CS for obstetrical indication at 23 weeks may improve neonatal outcome.     

Cross-cultural comparison of the attitudes of dental students in three countries

The aim of this study was to identify and compare the attitudes of dental students toward their career choice and dental education in three different countries. Three hundred thirty-six dental students from the University of British Columbia, Canada; Mahidol University and Chiang Mai University, Thailand; and Nippon Dental University, Japan, participated in this study. Information was derived from a questionnaire consisting of career choice items and dental education items. Significant differences in the responses of the participants from each of the three countries were detected for each of the questionnaire items (P<0.001). Regarding factors that may have served as motivations for career choice, the majority of dental students from each country indicated positive reasons such as interpersonal motives, caring for other people, and academic interest. For future career options, the majority of Japanese and Canadian students planned to work as general dentists. Thai students were more likely than Japanese or Canadian to prefer specialization than practicing general dentistry. Nearly three-quarters of the Canadian and Thai students were satisfied with the teaching faculty of their schools, while only a quarter of the Japanese students indicated satisfaction. The findings from this study enhance our understanding of differences and/or similarities among dental students in three nations; this information may help to define strategies to improve the quality of international student exchange programs.     

Heat of supersaturation-limited amyloid burst directly monitored by isothermal titration calorimetry

Amyloid fibrils form in supersaturated solutions via a nucleation and growth mechanism. Although the structural features of amyloid fibrils have become increasingly clearer, knowledge on the thermodynamics of fibrillation is limited. Furthermore, protein aggregation is not a target of calorimetry, one of the most powerful approaches used to study proteins. Here, with β₂-microglobulin, a protein responsible for dialysis-related amyloidosis, we show direct heat measurements of the formation of amyloid fibrils using isothermal titration calorimetry (ITC). The spontaneous fibrillation after a lag phase was accompanied by exothermic heat. The thermodynamic parameters of fibrillation obtained under various protein concentrations and temperatures were consistent with the main-chain dominated structural model of fibrils, in which overall packing was less than that of the native structures. We also characterized the thermodynamics of amorphous aggregation, enabling the comparison of protein folding, amyloid fibrillation, and amorphous aggregation. These results indicate that ITC will become a promising approach for clarifying comprehensively the thermodynamics of protein folding and misfolding.Aggregation has often been an obstacle to studying the structure, function, and physical properties of proteins. However, a large number of aggregates associated with serious diseases, including Alzheimer’s, Parkinson, and prion diseases (1, 2) promoted the challenge of studying protein misfolding and aggregation. Researchers succeeded in distinguishing amyloid fibrils and oligomers from other amorphous aggregates and characterized the ordered structures present in amyloid fibrils or oligomers, which led to the development of the field of amyloid structural biology (3–8). These advances have been attributed to various methodologies that are also useful for studying the structural properties of globular proteins. Even X-ray crystallography has become a powerful approach for studying amyloid microcrystals (5) or oligomers (9). The atomic details of amyloid fibrils are becoming increasingly clearer, and a cross-β structure was shown to be the main structural component of fibrils (5, 6, 8). Although tightly packed core regions of amyloid fibrils have been reported, the overall structures were shown to be dominated by common cross-β structures, which supported the argument for the main-chain dominated architecture in contrast to the side-chain dominated architecture of globular native states (10–12).These structural studies have been complemented by a series of efforts to clarify the mechanism for the formation of amyloid fibrils (i.e., amyloid fibrillation). The presence of a long lag time in spontaneous fibrillation and rapid fibrillation by the addition of preformed fibrils represent a similarity with the supersaturation-limited crystallization of substances (13–18). We have revisited “supersaturation” and argued its critical role for amyloid fibrillation (17–19). The role of supersaturation in neurodegenerative diseases at the proteome level has been reported recently (20).However, calorimetry, one of the most powerful methods used to study the thermodynamic properties of globular proteins (21–24), has not played a significant role in understanding protein aggregation. The aggregation of proteins following heat denaturation as monitored by differential scanning calorimetry is an infamous example demonstrating how aggregation can prevent exact analyses (25, 26). To date, few studies have investigated protein aggregation including amyloid fibrils with calorimetry (27–32). Our previous study on the exothermic heat effects accompanying fibril growth was achieved by monitoring the seed-dependent elongation of fibrils formed by β₂-microglobulin (β2m), a protein responsible for dialysis-related amyloidosis, using isothermal titration calorimetry (ITC) (28).In the present study using β2m, we succeeded in characterizing the total heat of spontaneous fibrillation and amorphous aggregation. An analysis of the heat burst associated with fibrillation or amorphous aggregation under various temperatures clarified their thermodynamic properties. The results obtained enabled the calorimetric characterization of amyloid fibrils and amorphous aggregates relative to that of the native globular structures, which opens a new field for the calorimetric study of protein aggregates.     

20-Hydroxyeicosatetraenoic acid stimulates nuclear factor-kappaB activation and the production of inflammatory cytokines in human endothelial cells

Endothelial dysfunction is associated with endothelial cell activation, i.e., up-regulation of surface cell adhesion molecules and the release of proinflammatory cytokines. 20-Hydroxyeicosatetraenoic acid (HETE), a major vasoactive eicosanoid in the microcirculation, has been implicated in the regulation of endothelial cell function through its angiogenic and pro-oxidative properties. We examined the effects of 20-HETE on endothelial cell activation in vitro. Cells transduced with adenovirus containing either CYP4A1 or CYP4A2 produced higher levels of 20-HETE, and they demonstrated increased expression levels of the adhesion molecule intercellular adhesion molecule (ICAM) (4-7-fold) and the oxidative stress marker 3-nitrotyrosine (2-3-fold) compared with cells transduced with control adenovirus. Treatment of cells with 20-HETE markedly increased levels of prostaglandin (PG) E(2) and 8-epi-isoprostane PGF(2alpha), commonly used markers of activation and oxidative stress, and most prominently, interleukin-8, a potent neutrophil chemotactic factor whose overproduction by the endothelium is a key feature of vascular injury. 20-HETE at nanomolar concentrations increased inhibitor of nuclear factor-kappaB phosphorylation by 2 to 5-fold within 5 min, which was followed with increased nuclear translocation of nuclear factor-kappaB (NF-kappaB). Likewise, 20-HETE activated the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway by stimulating phosphorylation of ERK1/2. Inhibition of NF-kappaB activation and inhibition of ERK1/2 phosphorylation inhibited 20-HETE-induced ICAM expression. It seems that 20-HETE triggers NF-kappaB and MAPK/ERK activation and that both signaling pathways participate in the cellular mechanisms by which 20-HETE activates vascular endothelial cells.     

In Vitro and In Vivo Antidermatophyte Activities of NND-502, a Novel Optically Active Imidazole Antimycotic Agent

In vitro and in vivo antidermatophyte activities of NND-502, a new imidazole antimycotic agent, were compared with those of two existing antifungal agents, lanoconazole and terbinafine. NND-502 exhibited strong in vitro antifungal activity against Trichophyton spp.; its MIC was 1 to 4 times lower than that of lanoconazole or terbinafine. In an in vivo study with a guinea pig model of tinea pedis, 7-day topical treatment with a 0.5% solution of NND-502 (dissolved in polyethylene glycol 400) was more effective than that with a 0.5% solution of either lanoconazole or terbinafine for eradicating fungi from the infected feet. When the duration of treatment was shortened to 3 days, a topical 1% solution of NND-502 achieved a complete mycological cure, while topical 1% solutions of lanoconazole and terbinafine did not.     

Quantitative CT measurements of small pulmonary vessels in chronic obstructive pulmonary disease: do they change on follow‐up scans?

The aims of this study were to perform a longitudinal evaluation of the cross‐sectional area (CSA) of small pulmonary vessels and the extent of emphysema measured on computed tomography (CT) scans of patients with chronic obstructive pulmonary disease (COPD), and to correlate the pulmonary vascular measurements with extent of emphysema. The institutional review board approved this retrospective study and waived the need for patients' informed consent. Seventy‐four patients with COPD who underwent both initial and follow‐up CT scans at an interval of ≥12 months were analysed. The CSA of small pulmonary vessels <5 mm² was measured, and the percentage of total CSA of the area of the lung (%CSA_<5) was calculated. The extent of emphysema was assessed as the percentage of low attenuation area (%LAA, <5 and %LAA during the follow‐up period was assessed using the Spearman rank correlation. The %LAA increased significantly on follow‐up CT scans (P<0·0001). The %CSA_<5 was slightly decreased on follow‐up scans, but the difference was not significant. Although longitudinal change in %LAA was positively correlated with duration of follow‐up period (ρ = 0·505, P<0·0001), longitudinal change in %CSA_<5 was not. In conclusion, there was a progressive increase in the extent of emphysema over time, but no significant decrease in the CSA of small pulmonary vessels over the same time period.