Adolescent insomnia as a risk factor for early adult depression and substance abuse

STUDY OBJECTIVE: To evaluate the association between adolescent insomnia and mental health during adolescence and young adulthood. DESIGN: Cross-sectional and prospective study. SETTINGS: School and in home. PARTICIPANTS: Nationally based population sample of 4494 adolescents, 12 to 18 years old at baseline (mean = 15.83 years), with 3582 young adults, 18 to 25 years old (mean = 21.25 years) at 6- to 7-year follow-up. MEASURES: Self-report measures of mental health. RESULTS: Insomnia symptoms were reported by 9.4% of the adolescents. Cross-sectionally, adolescent insomnia symptoms were associated with use of alcohol, cannabis, and drugs other than cannabis; depression; suicide ideation; and suicide attempts (all P values < 0.01) after controlling for sex. Prospectively, insomnia symptoms during adolescence were a significant risk factor for depression diagnosis (odds ratio = 2.3) in young adulthood after controlling for sex and baseline depression. CONCLUSION: This study is the first to longitudinally evaluate insomnia symptoms during adolescence as a risk factor for mental health problems in young adulthood. The findings indicate that insomnia is a prevalent problem for adolescents and argue for future treatment-outcome studies to evaluate the efficacy and effectiveness of various insomnia interventions in this age group.     

Inhibition of TNF-alpha secretion from peripheral blood monocular cells by triptolid is associated with TNF-alpha-308 gene polymorphisms in rheumatoid arthritis patients

This study examined the inhibitory effect of triptolid (TP) on tumor necrosis factor-α (TNF-α) secreted from peripheral blood monocular cells (PBMCs) and the association of the inhibitory effect with TNF-α-308 gene polymorphisms in rheumatoid arthritis (RA) patients. Gene polymorphism at A-G site 308 in the promoter region of TNF-α gene was detected in 42 RA patients by using allele specific polymerase chain reaction (AS-PCR) assay. PBMCs were harvested from these patients and treated first with lipopolysaccharides (LPS) and then with different doses of TP (1, 5.4 and 15 ng/mL). The TNF-α level in the supernatants was measured by enzyme-linked immunosorbent assay (ELISA). The results showed that TNF-α level in the supernatants of TP (1 ng/mL)-treated PBMCs was decreased by 3.80% and 4.91%, respectively, in the patients with AA and AG genotypes, when compared with those treated with LPS alone (P>0.05). Moreover, the TNF-α level in the patients with GG genotype was reduced by 20.74% (P<0.05). When PBMCs were treated with TP at 5.4 ng/mL, TNF-α levels in the patients with AA, AG, and GG genotypes were decreased by 20.42%, 34.73%, and 41.69%, respectively (P<0.05). The TNF-α level was slightly higher in the PBMCs treated with 15 ng/mL of TP than those in the two TP groups in the patients carrying AA, AG, and GG genotypes (P>0.05). It was concluded that gene polymorphism at TNF-α-308 sites may relate to the secretion of TNF-α in RA patients. TP has different inhibitory effects on the secretion of TNF-α in the patients harboring different genotypes, which may be one of the reasons for individual variation in response to TP.     

Data mining of microarray for differentially expressed genes in liver metastasis from gastric cancer

Tumor metastasis is the leading cause of death for gastric cancer. Metastasis is the main reason for the failure of clinical treatment for gastric cancer. In order to find metastasis-related genes and abnormal signal transduction pathway of high-invasive gastric cancer, samples of gastric cancer with liver metastasis were collected for microarray detection; up-regulated or down-regulated genes in all three cases were simultaneously screened out. Subsequently, from the preliminary screened genes, molecular pathways possibly impacting liver metastasis from gastric cancer were investigated by the Gene Cluster with Literature Profiles (GenCLip) analysis software. Many biological effects including apoptosis have been validated. Functional analysis of differentially expressed genes revealed that a variety of biological pathways, such as blood circulation and gas exchange, vasodilation and vasoconstriction regulation, and immune defense, could be significantly activated. Besides, gene sequences, specific keywords or gene regulatory networks were further searched by GenCLiP. We conclude that data mining allows to quickly identify a series of special signal transduction pathways involving abnormally expressed genes.     

Flow measurement by cardiovascular magnetic resonance: a multi-centre multi-vendor study of background phase offset errors that can compromise the accuracy of derived regurgitant or shunt flow measurements

Aims

Cardiovascular magnetic resonance (CMR) allows non-invasive phase contrast measurements of flow through planes transecting large vessels. However, some clinically valuable applications are highly sensitive to errors caused by small offsets of measured velocities if these are not adequately corrected, for example by the use of static tissue or static phantom correction of the offset error. We studied the severity of uncorrected velocity offset errors across sites and CMR systems.

Methods and Results

In a multi-centre, multi-vendor study, breath-hold through-plane retrospectively ECG-gated phase contrast acquisitions, as are used clinically for aortic and pulmonary flow measurement, were applied to static gelatin phantoms in twelve 1.5 T CMR systems, using a velocity encoding range of 150 cm/s. No post-processing corrections of offsets were implemented. The greatest uncorrected velocity offset, taken as an average over a ''great vessel'' region (30 mm diameter) located up to 70 mm in-plane distance from the magnet isocenter, ranged from 0.4 cm/s to 4.9 cm/s. It averaged 2.7 cm/s over all the planes and systems. By theoretical calculation, a velocity offset error of 0.6 cm/s (representing just 0.4% of a 150 cm/s velocity encoding range) is barely acceptable, potentially causing about 5% miscalculation of cardiac output and up to 10% error in shunt measurement.

Conclusion

In the absence of hardware or software upgrades able to reduce phase offset errors, all the systems tested appeared to require post-acquisition correction to achieve consistently reliable breath-hold measurements of flow. The effectiveness of offset correction software will still need testing with respect to clinical flow acquisitions.     

Level of agreement on postoperative complications after one-stage hypospadias correction comparing medical records and parent reports

PurposeTo analyze agreement on postoperative complications after hypospadias surgery according to medical records and parents' reports.Materials & methodsIn this retrospective cohort study, data were collected from 409 children who received an initial one-stage hypospadias correction in the Radboudumc, The Netherlands.Postoperative complications according to medical records were compared with parent-reported complications in an online questionnaire. Main complications studied were wound-related complications, urinary tract infections, fistulas, stenosis, and prepuce-related complications. Agreement was determined by Cohen's kappa coefficient.ResultsSlightly less complications were mentioned in medical records (37%) compared to parents' reports (42%). Overall agreement was moderate (κ = 0.50, 95% confidence interval (CI):0.41–0.59), but poor for some specific complications. Agreement was higher for complications that needed reoperation compared to when no reoperation was performed (κ = 0.53, 95% CI: 0.43–0.62 and κ = 0.18, 95% CI: 0.06–0.31) and for patients with recent surgery (< 5 years before questionnaire completion) compared to less recent surgeries (κ = 0.69, 95% CI: 0.55–0.84 and κ = 0.43, 95% CI: 0.33–0.54).ConclusionsAgreement on complications according to medical records and parents' reports was poor to moderate, but better after reoperation and more recent surgery. Some complications mentioned in medical records were missing from parents' reports and the other way around. Better agreement will give physicians and parents a more reliable view on postoperative outcome after hypospadias surgery.Type of studyDiagnostic test.Level of evidenceLevel III.     

Expression levels of genes likely involved in glucose-sensing in the obese Zucker rat brain

It has been suggested that certain cells in the brain, like pancreatic beta-cells, use glucose transporter-2 (GLUT-2), glucokinase and glucagon-like peptide-1 receptor (GLP-1R) to sense glucose in the service of multiple aspects of energy balance. The obese Zucker rat displays numerous disturbances in energy homeostasis and may provide a model of dysfunctional expression of genes related to nutrient control systems. Using real-time RT-PCR we measured gene expression for three of the pancreatic glucose-sensing markers and neuropeptide Y (NPY) in the medial, lateral hypothalamus and hindbrain of lean and obese Zucker rats of both genders. Additionally, we measured circulating levels of glucose, leptin, insulin, corticosterone and glucagon. The results indicate that GLUT-2 mRNA expression is decreased, whereas glucokinase is increased in the hindbrain of obese rats. NPY mRNA level is significantly higher, whereas GLP-1R is significantly lower in the medial hypothalamus in obese individuals. Gender-related differences were found in the hindbrain and medial hypothalamus for GLUT-2 and in the lateral hypothalamus for GLP-1R and they may be related to the fact that the female Zucker rats do not develop diabetes as readily as males. Furthermore, the hindbrain may be an important site for glucose-sensing where major phenotypic changes occur for glucose-sensing genes expression.     

Evidence for hypothalamic K+(ATP) channels in the modulation of glucose homeostasis

Several lines of evidence support the hypothesis that ATP-sensitive K+ channels (K+(ATP)) participate in the brain's regulation of peripheral glucose homeostasis. In testing this hypothesis we conducted a series of in vivo experiments using albino rats and bilateral intrahypothalamic injections of K+(ATP) channel blockers, glibenclamide and repaglinide. The results show that 0.2 and 2.0 nM injections of glibenclamide lowered blood glucose in a dose-dependent manner. During mild insulin-induced hypoglycemia, hypothalamic glibenclamide delayed recovery to normoglycemia. The impaired recovery was associated with a reduction in plasma norepinephrine (P<0.001), though circulating epinephrine and glucagon were not reduced. In a separate experiment, 2-deoxy-D-glucose (200 mg/kg) was intraperitoneally administered to produce neuroglucopenia. Hypothalamic injections of either glibenclamide or repaglinide significantly blunted compensatory hyperglycemic responses (P<0.01). In a feeding study, 2.0, but not 0.2 nM of hypothalamic glibenclamide, reduced chow intake over a 2-h period (P<0.01). The results support the hypothesis that hypothalamic K+(ATP) channels participate in central glucose-sensing and glucose regulation.