Together at school intervention programme. A pilot study on the feasibility and perceived benefits of a programme focusing on improving socio-emotional skills among schoolchildren in Finland

The aim of the Together at School Intervention Programme developed for the Finnish school system was to improve socio-emotional skills and prevent psychosocial problems among children (7?12 years). The aim of this pilot study was to evaluate the feasibility, safety and perceived benefits of the programme in order to justify its large-scale implementation for a randomized controlled study. Altogether, 23 classrooms from Grades 1–6 (N = 549, n = 451 children) in four schools participated in the study. Informants were teachers (n = 23), head masters (n = 4), children (n = 451) and their parents. Data were collected by questionnaires at three time points. The different tools assessed were considered to be beneficial for the children by 92?100% of the teachers, and pleasant to participate in by 73?89% of the children. During the follow-up, emotional symptoms reduced significantly among boys. Bullying behaviour was significantly reduced according to both teachers and children. The findings of this pilot study were encouraging.     

Novel spectral indexes of heart rate variability as predictors of sudden and non-sudden cardiac death after an acute myocardial infarction

BACKGROUND: Various indexes of 24-hour heart rate variability (HRV) have been able to predict all-cause mortality after an acute myocardial infarction (AMI), but their value in predicting specific modes of cardiac death has been limited. AIM: The aim of this study was to assess the role of two novel spectral indexes of HRV as predictors of either sudden (SCD) or non-sudden cardiac death after an AMI. Method. We used two novel methods of spectral analysis of HRV: 1) the high-frequency (HF) spectral component, V(index), calculated as an average HF power from the most linear portion of HF power versus the R-R interval regression curve, and 2) the prevalent low-frequency oscillation of heart rate (PLF). V(index), conventional HRV measures, and PLF were analyzed from 24-hour Holter recordings of 590 patients with a recent AMI. RESULTS: During the mean follow-up of 39+/-14 months, SCD occurred in 3% (n = 17) and non-sudden cardiac death in 5% (n = 28) of the patients. In univariate analysis, V(index) was the most potent predictor of SCD (RR: 6.0, 95% CI: 1.7-20.7, P<0.01), also remaining the most powerful predictor of SCD after adjustment for clinical variables and ejection fraction (RR: 4.2, 95% CI: 1.2-15.2, P<0.05). PLF was a potent predictor of non-sudden cardiac death (RR: 13.9, 95% CI: 5.9-32.5, P<0.001), but it did not predict SCD. CONCLUSIONS: Novel spectral HRV analysis methods, V(index) and PLF, provide significant information of the risk of the specific mode of death after an AMI.     

Pharmacokinetics and pharmacodynamics of pravastatin in pediatric and adolescent cardiac transplant recipients on a regimen of triple immunosuppression

BACKGROUND: In adults, pravastatin reduces the development and progression of transplant vasculopathy, the main long-term risk after cardiac transplantation. The pharmacokinetics of pravastatin is not known in children taking calcineurin inhibitors. Our aim was to determine the single-dose pharmacokinetics and short-term safety of pravastatin in children undergoing regular triple-drug immunosuppressive therapy after cardiac transplantation. METHODS: Nineteen pediatric cardiac transplant recipients (aged 4.4 to 18.9 years) receiving triple immunosuppression therapy consisting of methylprednisolone (19 patients), cyclosporine (INN, cyclosporin) (17 patients) or tacrolimus (2 patients), and azathioprine (18 patients) or mycophenolate mofetil (1 patient) ingested a single 10-mg dose of pravastatin, and plasma pravastatin concentrations were measured up to 24 hours. Subsequently, the patients took 10 mg pravastatin orally once daily for 8 weeks. The lipid-lowering effect and the safety of pravastatin therapy were studied. RESULTS: The mean peak plasma concentration (C(max)) of pravastatin was 122.2 +/- 88.2 ng/mL (range, 11.4-305.0 ng/mL), and the area under the plasma concentration-time curve of pravastatin from 0 to 10 hours [AUC(0-10)] was 264.1 +/- 192.4 ng.h/mL (range, 30.8-701.6 ng.h/mL). These C(max) and AUC(0-10) values are nearly 10-fold higher than the corresponding values reported in hypercholesterolemic children in the absence of immunosuppressive therapy. The time of peak concentration (t(max)) of pravastatin was 1.1 +/- 0.4 hours (range, 0.5-2 hours), and the mean elimination half-life (t(1/2)) was 1.2 +/- 0.3 hours (range, 0.7-2.2 hours); these parameters were similar to those in the hypercholesterolemic children. By 8 weeks of treatment, the concentration of serum total cholesterol decreased by 13% (P =.005), low-density lipoprotein cholesterol by 27% (P <.0001), and triglycerides by 6% (not significant, P =.28); the concentration of high-density lipoprotein cholesterol increased by 7% (not significant, P =.30). No clinically significant increases in serum ALT, creatine kinase, or creatinine levels were observed. CONCLUSIONS: The plasma concentrations of pravastatin in pediatric cardiac recipients receiving triple immunosuppressive medication are nearly 10-fold higher than in hypercholesterolemic children after the same pravastatin dose. However, the short-term therapy of pravastatin was well tolerated and effective in lowering serum cholesterol levels in cardiac recipients.     

Geographical variation in incidence of primary total hip arthroplasty: a population-based analysis of 34,642 replacements

Background  

Considerable variation in total hip arthroplasty (THA) incidence between regions has been described. The aim of this study was to evaluate geographical variation in the incidence of primary THA for OA in Finland and to analyze variables associated with this variation.     

No association between high temperature requirement 1 (HTRA1) gene polymorphisms and Alzheimer's disease

High temperature requirement 1 (HTRA1) gene is a plausible risk factor in Alzheimer's disease (AD) as it encodes a protease known to degrade amyloid-β peptide. Here we have studied whether single nucleotide polymorphisms (SNPs) in the HTRA1 gene or its nearby regions associated with AD in a large clinic-based case-control cohort originating from Finland. We did not observe significant association of the HTRA1 SNPs with AD among the whole case-control cohort or age-at-onset risk effect among AD patients.     

Cofilin regulator 14-3-3zeta is an evolutionarily conserved protein required for phagocytosis and microbial resistance

Phagocytosis is an ancient cellular process that plays an important role in host defense. In Drosophila melanogaster phagocytic, macrophage-like hemocytes recognize and ingest microbes. We performed an RNAi-based in vitro screen in the Drosophila hemocyte cell line S2 and identified Abi, cpa, cofilin regulator 14-3-3ζ, tlk, CG2765, and CG15609 as mediators of bacterial phagocytosis. Of these identified genes, 14-3-3ζ had an evolutionarily conserved role in phagocytosis: bacterial phagocytosis was compromised when 14-3-3ζ was targeted with RNAi in primary Drosophila hemocytes and when the orthologous genes Ywhab and Ywhaz were silenced in zebrafish and mouse RAW 264.7 cells, respectively. In Drosophila and zebrafish infection models, 14-3-3ζ was required for resistance against Staphylococcus aureus. We conclude that 14-3-3ζ is essential for phagocytosis and microbial resistance in insects and vertebrates.     

Aging is associated with quantitative and qualitative changes in circulating cell-free DNA: the Vitality 90+ study

As a marker of cellular death, cell-free DNA (cf-DNA) has a utility in diagnosis and prognosis of various disorders. Since aging accompanies increased cellular senescence and death, we aimed to characterize potential age-related alterations in cf-DNA. The study population consisted of 12 nonagenarian women (participants in the Vitality 90+ Study) and 11 healthy control women (aged 22-37 years). Some of the nonagenarians (n=8) were also recruited for follow-up after one year. cf-DNA was extracted using two different methods. Total cf-DNA was quantified directly in plasma and the amplifiable cf-DNA was assessed using quantitative PCR. Quality of cf-DNA was analysed with a DNA Chip assay. For all the quantification methods, the concentration of cf-DNA was significantly higher (p<0.05) in nonagenarians as compared to controls. The quality of the cf-DNA also displayed a marked difference between nonagenarians and controls; a fragmented pattern or appearance of low molecular weight cf-DNA was observed in the majority of the nonagenarians, whereas in controls, cf-DNA was intact and had a quasi-genomic, high molecular weight appearance. In nonagenarians, the quality of cf-DNA appeared similar in the original and follow-up samples. We propose that some, as yet uncharacterized, aspects of aging are reflected in the appearance of cf-DNA.     

Ultrasmall and customizable multichannel electrodes for extracellular recordings

Increasing demand exists for smaller multichannel electrodes that enable simultaneous recordings of many neurons in a noninvasive manner. We report a novel method for manufacturing ultrasmall carbon fiber electrodes with up to seven closely spaced recording sites. The electrodes were designed to minimize damage to neuronal circuitry and to be fully customizable in three dimensions so that their dimensions can be optimally matched to those of the targeted neuron population.