Clinical associations of prenatal ischaemic white matter injury

Neuropathological examinations were carried out at necropsy on 274 cases of intrauterine death or neonatal death at or before three days after birth. Fifty six (20.4%) subjects had evidence of prenatal ischaemic brain damage. On review of the maternal case notes to ascertain antenatal clinical associations there was an increased incidence of intrauterine growth retardation, either based on birth weight for gestational age (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.1 to 3.7) or diagnosed antenatally (OR 2.7; 95% CI 1.3 to 5.6). Oligohydramnios was also more common (OR 2.9; 95% CI 1.2 to 7.0). The association of intrauterine growth retardation and white matter damage remained after excluding fetuses with a major congenital anomaly (OR 2.4; 95% CI 1.1 to 5.1). The findings suggest that chronic intrauterine hypoxia may be associated with damage to cerebral white matter among fetuses and infants who die. The relation between ischaemic white matter damage and cerebral palsy among survivors remains speculative.     

Hearing impairment fitting: study of an auditory prosthesis with 7 entirely programmable filters

We designed a 7-filter digital auditory prosthesis table prototype. For each of these filters frequency band width, amplification and compression were programmable in order to adapt these parameters to the deaf patient's audiometric particularities. We compared the hearing improvement it was possible to obtain with our prototype as a function of the number of filters (3, 4 or 7) and their frequency band width programmability. We tested 21 patients suffering from middle or severe neurosensory hearing loss. This study allows to demonstrate that a 7 programmable-width-filter strategy seems to be the most appropriate.     

Rethinking infant knowledge: toward an adaptive process account of successes and failures in object permanence tasks

Infants seem sensitive to hidden objects in habituation tasks at 3.5 months but fail to retrieve hidden objects until 8 months. The authors first consider principle-based accounts of these successes and failures, in which early successes imply knowledge of principles and failures are attributed to ancillary deficits. One account is that infants younger than 8 months have the object permanence principle but lack means-ends abilities. To test this, 7-month-olds were trained on means-ends behaviors and were tested on retrieval of visible and occluded toys. Means-ends demands were the same, yet infants made more toy-guided retrievals in the visible case. The authors offer an adaptive process account in which knowledge is graded and embedded in specific behavioral processes. Simulation models that learn gradually to represent occluded objects show how this approach can account for success and failure in object permanence tasks without assuming principles and ancillary deficits.     

Monocyte diapedesis through an in vitro vessel wall construct: inhibition with monoclonal antibodies to thrombospondin

Human peripheral blood monocytes were examined for migration across an endothelial cell monolayer in an in vitro vessel wall construct. Few monocytes invaded in the absence of a chemotactic gradient, despite significant adhesion to the endothelial monolayer. However, the addition of zymosan-activated human plasma to the lower compartment, to create a chemotactic gradient across the vessel wall, resulted in significantly enhanced monocyte migration. Pretreatment of the monocytes with monoclonal antibodies to thrombospondin (TSP) dramatically inhibited monocyte diapedesis into the vessel wall. The same treatment inhibited monocyte adhesion to endothelial cells in two-dimensional monolayer cultures as well as in vessel wall constructs (no chemotactic gradient). Of interest, however, the monoclonal antibodies had no inhibitory effect on monocyte migration into collagen gels devoid of endothelial cells in response to the same chemotactic gradient, suggesting the importance of TSP in monocyte-endothelial cell interactions. Monoclonal antibodies to fibronectin and normal mouse immunoglobulin G did not inhibit migration in this model of a vessel wall. Furthermore, monoclonal antibodies to TSP showed no inhibition of human peripheral blood neutrophil migration. Previous studies have shown that monocytes synthesize TSP and express this moiety on their surface. The present data suggest that monocytes may utilize TSP to interact with endothelial cells lining the vessel wall during diapedesis.     

Low density lipoprotein catabolism is enhanced by the cleaved form of alpha-1-antitrypsin

The frequent occurrence of hypocholesterolaemia following inflammatory processes is well known but unexplained. Elevated plasma levels of serine proteinase inhibitors (serpins) and their complexes with target enzymes have been demonstrated in inflammatory, malignant and infectious diseases which are also often accompanied by low plasma cholesterol levels. Under inflammatory conditions, uncomplexed, but cleaved inactive serpins arising from slow deacylation of the serpin-proteinase complex may be present in the circulation. To determine the influence of native and cleaved forms of serpins, such as alpha-1-antitrypsin (AAT), on lipoprotein metabolism, we investigated the effect of these forms on low density lipoprotein (LDL) catabolism in human HepG2 cell line. We have found that the cleaved form of AAT in concentrations from 125 to 2000 nmol l-1 stimulates LDL binding to the HepG2 cells, by up to 49% with a subsequent increase in LDL uptake and degradation of up to 79 and 65% respectively. Native AAT was also found to increase LDL binding and internalization by 20-25%, independently of the amount of AAT added, an effect most probably due to the cleaved form of AAT produced by local proteolysis of native AAT incubated in the cell culture. Moreover we have shown that the cleaved form of AAT interacts with LDL in vitro, and that such an interaction abolishes AAT ability to stimulate LDL binding and internalization. This study for the first time describes the ability of the cleaved form of AAT to stimulate LDL binding and internalization in HepG2 cell culture, and provides evidence that hypocholesterolaemia occurring during inflammatory processes may be mediated by cleaved forms of serpins.     

Stressful life events and smoking behaviors in Chinese adolescents: a longitudinal analysis.

The associations between stressful life events and smoking have been established among adolescents in the United States. However, whether these relationships are similar in adolescents from other non-Western cultures is unknown. Understanding these relationships in adolescents may help to provide opportunities to reduce the smoking rates in those cultures by providing positive coping methods that do not include smoking. In this longitudinal study, the associations between nine stressful life events scales and smoking behaviors were examined in a sample of Chinese adolescents. Six of these scales, positive school-related, negative school-related, positive family-related, positive peer-related, negative peer-related, and negative health-related had significantly different means among females and males. Among males, positive school-related stress was a protective factor for smoking susceptibility. Among females, positive school-related stress was a protective factor and negative school-related stress was a risk factor for lifetime smoking, and negative family-related stress was a risk factor for smoking susceptibility. Findings indicate that smoking among male adolescents in China may not be the result of stress; however, in females stress may contribute to the decision to smoke. Future directions are discussed.