Associations between fibroblast growth factor 23 and cardiac characteristics in pediatric heart failure

Background

In adults with heart failure, elevated levels of fibroblast growth factor 23 (FGF23) are associated with mortality. Data on FGF23 levels in pediatric heart failure are lacking.

Patients and methods

We conducted a cross-sectional study of 17 healthy children (mean age 13 years) and 20 pediatric patients with heart failure (mean age 12 years) who underwent echocardiography and for whom the following measurements were taken: plasma FGF23 and parathyroid hormone (PTH) and serum phosphate, creatinine and N-terminal prohormone brain natriuretic peptide (NT-proBNP). Symptom severity was assessed with the New York Heart Association and the Ross classification systems.

Results

Of the 20 patients, 11 had dilated cardiomyopathy, four had congenital heart disease, three had hypertrophic cardiomyopathy, one had a failing heart transplant and one had pulmonary hypertension. Mean phosphate levels in these patients were within the reported reference range for healthy children. Median PTH levels were in the normal range in patients and controls. The median FGF23 level was higher in patients versus controls (110.9 vs. 66.4 RU/ml; P?=?0.03) and higher in patients on diuretics versus other patients (222.4 vs. 82.1 RU/ml; P?=?0.01). Levels of FGF23 and NT-proBNP were directly correlated (r?=?0.47, P?=?0.04), and patients with greater physical functional impairment had higher FGF23 levels (142.5 in those with moderate-severe limitation vs. 92.8 RU/ml in those with no limitation; P?=?0.05). Among patients with dilated cardiomyopathy, higher FGF23 levels were associated with a greater left ventricular end-diastolic diameter (r?=?0.63, P?=?0.04).

Conclusion

FGF23 levels are elevated in children with heart failure and are associated with diuretic use, severity of heart failure and left ventricular dilation.     

Waste of skin in elliptical excision biopsy of non-melanomatous skin cancer

Our objective was to quantify the skin wasted during elliptical excision biopsy. This is defined as the difference between the excised elliptical area and the area of the original lesion. We used geometrical calculations of 26 excisional biopsy specimens from patients with non-melanomatous malignant tumours. Relative to the lesion area, the largest waste of skin measured was 230% and the smallest was 34% with a mean of 130%. We conclude that for better preservation of tissue when closing circular defects, patterns other than an ellipse should be adopted.     

Ethical Considerations in Conducting Research on Autism Spectrum Disorders in Low and Middle Income Countries

Autism spectrum disorder (ASD) is being identified in an ever-increasing number of countries, including many that are low or middle income (LMIC). Research conducted in these countries requires awareness of unique ethical issues. Drawing on the experience of two organizations that have been involved in conducting and collaborating in ASD research in India, we describe specific considerations in conducting epidemiological, genetic and treatment studies as well as general principles from the field of multinational clinical research as they apply to the conduct of ASD research. We argue that greater attention to ethical concerns will result in quality studies conducted in LMICs that are also of greatest relevance for families and children with ASD.     

Error self-regulation following traumatic brain injury: A single case study evaluation of metacognitive skills training and behavioural practice interventions

The objective of the study was to evaluate the effects of metacognitive skills training (MST) and behavioural practice on error self-regulation during a naturalistic task after traumatic brain injury (TBI). A single-case study design was used and three participants (two males, one female) aged 26–43 years with severe TBI were included in the study. In the first study, after a four-session baseline of behavioural practice, two participants received eight MST sessions followed by four maintenance sessions. In the second study, a third participant received 16 sessions of behavioural practice to assess the extent to which error self-regulation improves through long-term task practice and therapist corrections. Participants prepared two different meals with a novel meal introduced later to examine skills generalisation. Behavioural outcomes included error frequency, checking and self-corrections. Data analysis involved a combination of visual analysis and two standard deviation (2-SD) band analysis. In the MST study, the two participants demonstrated a 38% and 76% reduction in error frequency (p < .05), a significant decrease in checks (p < .05), and a significant increase in self-corrections (p < .05) relative to baseline. In the behavioural practice study, the participant demonstrated reduced errors (25%), although this was not statistically significant, and a significant increase in checks (p < .05), but self-corrections did not significantly change (p > .05). This exploratory research suggests that, firstly, by targeting error self-regulation MST can potentially promote independence on complex everyday tasks; and secondly, although behavioural practice alone may facilitate some functional gains, it fails to promote more independent self-regulatory behaviours.     

Influence of Intra- and Extracellular Acidification on Free Radical Formation and Mitochondria Membrane Potential in Rat Brain Synaptosomes

Brain ischemia is accompanied by lowering of intra- and extracellular pH. Stroke often leads to irreversible damage of synaptic transmission by unknown mechanism. We investigated an influence of lowering of pH_i and pH_o on free radical formation in synaptosomes. Three models of acidosis were used: (1) pH_o 6.0 corresponding to pH_i decrease down to 6.04; (2) pH_o 7.0 corresponding to the lowering of pH_i down to 6.92: (3) 1 mM amiloride corresponding to pH_i decrease down to 6.65. We have shown that both types of extracellular acidification, but not intracellular acidification, increase 2′,7′-dichlorodihydrofluorescein diacetate fluorescence that reflects free radical formation. These three treatments induce the rise of the dihydroethidium fluorescence that reports synthesis of superoxide anion. However, the impact of amiloride on superoxide anion synthesis was less than that induced by moderate extracellular acidification. Superoxide anion synthesis at pH_o 7.0 was almost completely eliminated by mitochondrial uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone. Furthermore, using fluorescent dyes JC-1 and rhodamine-123, we confirmed that pH_o lowering, but not intracellular acidification, led to depolarization of intrasynaptosomal mitochondria. We have shown that pH_o but not pH_i lowering led to oxidative stress in neuronal presynaptic endings that might underlie the long-term irreversible changing in synaptic transmission.