Disruption of the sterol carrier protein 2 gene in mice impairs biliary lipid and hepatic cholesterol metabolism.

Hepatic up-regulation of sterol carrier protein 2 (Scp2) in mice promotes hypersecretion of cholesterol into bile and gallstone formation in response to a lithogenic diet. We hypothesized that Scp2 deficiency may alter biliary lipid secretion and hepatic cholesterol metabolism. Male gallstone-susceptible C57BL/6 and C57BL/6(Scp2(-/-)) knockout mice were fed a standard chow or lithogenic diet. Hepatic biles were collected to determine biliary lipid secretion rates, bile flow, and bile salt pool size. Plasma lipoprotein distribution was investigated, and gene expression of cytosolic lipid-binding proteins, lipoprotein receptors, hepatic regulatory enzymes, and intestinal cholesterol absorption was measured. Compared with chow-fed wild-type animals, C57BL/6(Scp2(-/-)) mice had higher bile flow and lower bile salt secretion rates, decreased hepatic apolipoprotein expression, increased hepatic cholesterol synthesis, and up-regulation of liver fatty acid-binding protein. In addition, the bile salt pool size was reduced and intestinal cholesterol absorption was unaltered in C57BL/6(Scp2(-/-)) mice. When C57BL/6(Scp2(-/-)) mice were challenged with a lithogenic diet, a smaller increase of hepatic free cholesterol failed to suppress cholesterol synthesis and biliary cholesterol secretion increased to a much smaller extent than phospholipid and bile salt secretion. Scp2 deficiency did not prevent gallstone formation and may be compensated in part by hepatic up-regulation of liver fatty acid-binding protein. These results support a role of Scp2 in hepatic cholesterol metabolism, biliary lipid secretion, and intracellular cholesterol distribution.

Acute partial paralysis alters perceptions of air hunger, work and effort at constant P(CO(2)) and V(E).

Breathing sensations of AIR HUNGER, WORK and EFFORT may depend on projections of central motor discharge (corollary discharge) to the forebrain. Source of motor drive (brainstem or cortex) may determine what is perceived. To test the effect of changing motor discharge at constant ventilation, we induced partial neuromuscular blockade during hypercapnic hyperpnea (31 + or - 9 L min(-1); PET(CO(2))=49 + or - 2 Torr) and during matched volitional hyperpnea (34 + or - 5 L min(-1); PET(CO(2))=41 + or - 1 Torr). Decline of vital capacity was similar between conditions (39%). Ventilation was unchanged with paralysis, indicating increased respiratory motor drive to maintain hyperpnea. Sensations were rated on a seven point ordinal scale. Median EFFORT and WORK increased 3-3.5 points with paralysis during both forms of hyperpnea (P<0.02, Wilcoxon signed rank). Median AIR HUNGER increased 2.5 points with paralysis during hypercapnic (P<0.02) but not during volitional hyperpnea. Data suggests that EFFORT and WORK arise from motor cortex activity (subjects reported engaging volitional control when paralyzed even during hypercapnia) and suggests that AIR HUNGER arises from medullary motor activity.

Estimating sleep patterns with activity monitoring in children and adolescents: how many nights are necessary for reliable measures?

STUDY OBJECTIVES: This study provides estimates of reliability for aggregated values from 1 to 7 recording nights for five commonly used actigraphic measures of sleep patterns, reliability as a function of night type (weeknight or weekend night), and stability of measures over several months. DESIGN AND SETTING: Data are from three studies that obtained 7 nights of actigraph data (using Mini Motionlogger actigraphs and associated validated algorithms [ASA]) on children and adolescents living at home on self-selected sleep-wake schedules. PARTICIPANTS: Participants were 169 children aged 12-60 months, and 55 adolescents aged 11-16 years. MEASUREMENTS AND RESULTS: Up to 28% of weekly recordings may be unacceptable for analysis in young participants because of illness, technical problems, and participant noncompliance; studies aiming to collect 5 nights of actigraph data should record for at least 1 full week. Reliability estimates for values aggregated over any 5 nights were adequate (> or = .70) for sleep start time, wake minutes, and sleep efficiency. Measures of sleep minutes and sleep period were less reliable and may require 7 or more nights for estimates of stable individual differences. Reliability for 1- or 2-night aggregates were poor for all measures. We found significant and high correlations between summer and fall session measures for all five variables when weekend nights were included. CONCLUSIONS: Five or more nights of usable recordings are required to obtain reliable actigraph measures of sleep for children and adolescents.

[Cognitive procedures in psychiatric rehabilitation]. / Kognitive Verfahren in der psychiatrischen Rehabilitation.

The legal requirements and research work done until now on rehabilitative cognitive methods will be critically reviewed in terms of possible therapeutic achievements. Cognitive deficits, like attention and concentration disturbances and abstract and differentiation ability, can be improved clearly by these therapy programs; however, a remission cannot be achieved.