| 1. |
- Campbell, Ian, et al.
(författare)
-
The relation between the age at diagnosis of problem behaviors related to aggression and distal outcomes in Swedish children
- 2019
-
Ingår i: European Child and Adolescent Psychiatry. - : Springer. - 1018-8827 .- 1435-165X. ; 28:7, s. 899-911
-
Tidskriftsartikel (refereegranskat)abstract
- Severe childhood aggressive behaviors are known to predict negative outcomes later in life; however, little is known about the effect of when in childhood aggression problems are diagnosed. While an earlier first diagnosis of problematic aggressive behavior might be associated with increased severity and, thus, worse outcomes, it is also possible that an earlier diagnosis affords an earlier start of treatment programs or indicates that greater attention is being paid to behavioral problems, thus resulting in attenuation of the severity of childhood aggression's impact on distal outcomes. The current study analyzed data from the population-based Swedish Data Registries, which include data on all children formally diagnosed by the Swedish medical system with a wide range of aggression problems between ages 8 and 18 (N = 5816) during the years 1987-2013, along with a matched control. Time-to-event analyses investigated whether the age at time of diagnosis affects later life outcomes while controlling for relevant confounders. Results show that for both boys and girls, those with a later diagnosis had lower average incomes (regression coefficient b = - 0.055, p < 0.005) and a higher probability of having a criminal record (odds ratio 1.126, p < 0.005) than children with earlier diagnoses. The effect on suicide attempts was not significant after correcting for multiple testing (odds ratio 1.264, p = 0.016). Grade score was not significantly affected. The results warrant further research concerning the potential advantage of earlier diagnoses, especially concerning generalizability beyond the Swedish population.
|
|
| 2. |
- Gurung, Iman S., et al.
(författare)
-
Deletion of the metabolic transcriptional coactivator PGC1β induces cardiac arrhythmia
- 2011
-
Ingår i: Cardiovascular Research. - : Oxford University Press. - 0008-6363 .- 1755-3245. ; 92:1, s. 29-38
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: Peroxisome proliferator-activated receptor-γ coactivators PGC1α and PGC1β modulate mitochondrial biogenesis and energy homeostasis. The function of these transcriptional coactivators is impaired in obesity, insulin resistance, and type 2 diabetes. We searched for transcriptomic, lipidomic, and electrophysiological alterations in PGC1β(-/-) hearts potentially associated with increased arrhythmic risk in metabolic diseases.METHODS AND RESULTS: Microarray analysis in mouse PGC1β(-/-) hearts confirmed down-regulation of genes related to oxidative phosphorylation and the electron transport chain and up-regulation of hypertrophy- and hypoxia-related genes. Lipidomic analysis showed increased levels of the pro-arrhythmic and pro-inflammatory lipid, lysophosphatidylcholine. PGC1β(-/-) mouse electrocardiograms showed irregular heartbeats and an increased incidence of polymorphic ventricular tachycardia following isoprenaline infusion. Langendorff-perfused PGC1β(-/-) hearts showed action potential alternans, early after-depolarizations, and ventricular tachycardia. PGC1β(-/-) ventricular myocytes showed oscillatory resting potentials, action potentials with early and delayed after-depolarizations, and burst firing during sustained current injection. They showed abnormal diastolic Ca(2+) transients, whose amplitude and frequency were increased by isoprenaline, and Ca(2+) currents with negatively shifted inactivation characteristics, with increased window currents despite unaltered levels of CACNA1C RNA transcripts. Inwardly and outward rectifying K(+) currents were all increased. Quantitiative RT-PCR demonstrated increased SCN5A, KCNA5, RYR2, and Ca(2+)-calmodulin dependent protein kinase II expression.CONCLUSION: PGC1β(-/-) hearts showed a lysophospholipid-induced cardiac lipotoxicity and impaired bioenergetics accompanied by an ion channel remodelling and altered Ca(2+) homeostasis, converging to produce a ventricular arrhythmic phenotype particularly during adrenergic stress. This could contribute to the increased cardiac mortality associated with both metabolic and cardiac disease attributable to lysophospholipid accumulation.
|
|
