L ymphangioleiomyomatosis (LAM) is a rare, progressive, frequently fatal cystic lung disease that affects women almost exclusively. 1,2 LAM occurs in up to 40% of women with tuberous sclerosis complex (TSC-LAM), 3-5 a tumor suppressor syndrome associated with seizures, cognitive impairment, and hamartomas in multiple organs, and in a nonheritable sporadic form (S-LAM) that involves only the lung,
Mild sleep restriction for 5 days impairs reaction times during working memory tasks in adolescents in the absence of increased perception of sleepiness.
Wolbachia pipientis Hertig and Wolbach (Rickettsiales: Rickettsiaceae) are intracellular α-proteobacteria that occur naturally in Aedes albopictus (Skuse) (Diptera: Culicidae) and numerous other invertebrates. These endosymbionts can invade host populations by manipulating host reproduction. Wolbachia infections have been shown to impart both costs and benefits to hosts in terms of development, survival, and fecundity. Here, we monitor intraspecific competition among independent cohorts of infected or uninfected larvae. Levels of competition are manipulated by varying initial larval densities and food levels. Although larval density is observed to have major impacts on immature survivorship, sex ratio of eclosing adults, and developmental rates, the Wolbachia infection status had minimal impact on male immatures and no effect on immature females under these experimental conditions. Female and male immatures were observed to respond differently to competitive pressure, with the functional relationships of females and males consistent with scramble and contest competition, respectively. The results are discussed in relation to the evolution of naturally occurring Wolbachia infections in Ae. albopictus (i.e., natural population replacement events) and public health strategies that propose the manipulation of Wolbachia infections in Ae. albopictus populations.
Rationale: We previously demonstrated that children with obstructive sleep apnea have increased blood pressure associated with changes in left ventricular mass index. Others have shown in adults that blood pressure variability is an important predictor of changes in left ventricular mass. The baroreflex system buffers blood pressure changes by varying heart rate. We have thus hypothesized that (1) baroreflex system gain is increased during sleep, improving blood pressure buffering; (2) children with obstructive sleep apnea lack this baroreflex gain increase; and (3) reduced blood pressure buffering results in exaggerated blood pressure variability that is associated with end-organ damage. Objectives: Compare measures of left ventricular mass index and nighttime baroreflex gain of healthy children to those of children with obstructive sleep apnea. Methods: A total of 169 children (50 control subjects, 63 with mild obstructive sleep apnea, and 56 with severe obstructive sleep apnea) with a mean age of 9.9 years (62.2) underwent echocardiography followed by polysomnography with continuous blood pressure measurement. Baroreflex gain was calculated in time and frequency domains. Measurements and Main Results: Healthy children demonstrated a nighttime pattern of increasing baroreflex gain. Children with obstructive sleep apnea had decreased nighttime baroreflex gain compared with control subjects. Nighttime blood pressure and blood pressure variability were significantly correlated with left ventricular mass index. Conclusions: Obstructive sleep apnea is associated with a decrease in nighttime baroreflex gain and an increase in blood pressure variability. This increase is correlated with changes in left ventricular mass index.Keywords: sleep; apnea; baroreceptor; blood pressure Numerous studies show that adults with obstructive sleep apnea (OSA) commonly have associated impairment of cardiovascular autonomic control (1-5). Beat-to-beat heart rate variability is diminished while sympathetic nerve activity and blood pressure (BP) are increased. Although the mechanisms linking OSA to cardiovascular pathology remain unclear, OSA is an identified cause of hypertension in adults (6, 7).Recently, as part of an ongoing National Institutes of Health protocol, we showed that children with OSA have elevated nighttime and diurnal BP (8). Other studies have shown that children with OSA have left ventricular remodeling (9), altered heart rate variability (10), and increased sympathetic activity (11). Together, these findings suggest that children with OSA may likewise suffer from cardiovascular autonomic control impairment.A critical component of cardiovascular autonomic control is the baroreflex system. This system provides the negative feedback control necessary to buffer BP fluctuations with accelerating or decelerating heart rate by changing the R-wave interval. The feedback is transmitted via the arterial baroreceptors, which are nerve fiber endings that respond to pressure-induced changes in circumferential stress of the majo...
Rationale: The efficacy of inhaled tobramycin on chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) has been established in clinical trials. However, little is known about its clinical effectiveness on lung function outside randomized controlled trial settings; conventional analysis of existing registry data has heretofore been confounded by treatment selection bias.Objective: To determine effectiveness of inhaled tobramycin on FEV 1 decline in patients with chronic P. aeruginosa infections using observational data from the Cystic Fibrosis Foundation Patient Registry.Methods: Patient-level tobramycin use was measured at first chronic P. aeruginosa infection (n = 13,686 patients; age, 6-21 yr). Decline in FEV 1 2 years after infection was estimated for patients treated with tobramycin and compared with untreated patients. Multiple linear regressions with confounder adjustment and propensity scores were used to estimate mean FEV 1 decline for each group. Because care is organized by centers, we used center-specific prescription rates as an instrument to reduce treatment-by-condition bias.Measurements and Main Results: Using center-level prescribing rates, instrumental variables analysis showed less FEV 1 decline for patients who received tobramycin when first eligible compared with those who did not receive tobramycin (difference, 2.55% predicted; 95% confidence interval, 0.16-4.94; P = 0.0366).Conclusions: Inhaled tobramycin is effective in reducing lung function decline among patients 6 to 21 years of age with CF. Because CF care is organized by center, using center-specific prescription rates as an instrumental variable is a feasible approach to using the Cystic Fibrosis Foundation Patient Registry to determine treatment effectiveness. More generally, this approach can correct for treatment-by-condition bias arising from observational studies.
Contrary to expectations, sleep duration was not associated with metabolic outcomes, and showed limited associations with lipid profiles. Although inadequate sleep may affect other areas of functioning, it appears premature to expect that lengthening sleep will improve BMI or metabolic outcomes in clinical samples of obese adolescents.
Treatment of obstructive sleep apnea in children by adenotonsillectomy is associated with gradual improvement in known risk factors for cardiovascular disease. Complete normalization of baroreceptor sensitivity was not achieved 6 months postoperatively.
Rationale: An association between neurocognitive deficits and pediatric sleep-disordered breathing has been suggested; however, weak correlations between disease severity and functional outcomes underscore the lack of knowledge regarding factors modulating cognitive morbidity of sleep-disordered breathing. Objectives: To identify the parameters affected by sleep-disordered breathing that modulate cerebral oxygenation, an important determinant of cognition. A further objective was to use these parameters with demographic data to develop a predictive statistical model of pediatric cerebral oxygenation. Methods: Ninety-two children (14 control subjects, 32 with primary snoring, and 46 with obstructive sleep apnea) underwent polysomnography with continuous monitoring of cerebral oxygenation and blood pressure. Analysis of covariance was used to relate the blood pressure, sleep diagnostic parameters, and demographic characteristics to regional cerebral oxygenation. Measurements and Main Results: To account for anatomic variability, an index of cerebral oxygenation during sleep was derived by referencing the measurement obtained during sleep to that obtained during wakefulness. In a repeated measures model predicting the index of cerebral oxygenation, mean arterial pressure, rapid eye movement (REM) sleep, female sex, age, and oxygen saturation had a positive effect on cerebral oxygenation levels, whereas arousal index and non-REM (NREM) sleep had a negative effect. Conclusions: Increasing mean arterial pressure, age, oxygen saturation, and REM sleep augment cerebral oxygenation, while sleepdisordered breathing, male sex, arousal index, and NREM sleep diminish it. The proposed model may explain the sources of variability in cognitive function of children with sleep-disordered breathing.Keywords: children; sleep-disordered breathing; cerebral oxygenationThe pediatric syndrome of sleep-disordered breathing (SDB), which encompasses both primary snoring and obstructive sleep apnea (OSA), affects more than 12% of children (1, 2). Whereas children with primary snoring have only a limited number of obstructive airway events during sleep, those with OSA characteristically experience varying, but more frequent episodes of airway obstruction. Although cognitive deficits have been described in children with SDB, evidence of a causal relationship between SDB and these deficits has not been firmly established (3-9). The absence of a dose-dependent association of cognitive deficits with increasing severity of OSA, coupled with findings of cognitive deficits in children with primary snoring, has challenged the notion of an adverse effect of SDB on cognition (10, 11). To the contrary, however, SDB may indeed be causally related to the development of cognitive deficits, with the biological factors that modify its effect on cognition not yet identified.There is strong evidence that a sustained decrease of regional cerebral oxygen saturation (rS O 2 ) during cardiopulmonary bypass surgery in adults is related to postoperative decline in...
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