7 research outputs found
Maturation of the Cardiac Autonomic Nervous System Activity in Children and Adolescents
Background
Despite the increasing interest in cardiac autonomic nervous activity, the normal development is not fully understood. The main aim was to determine the maturation of different cardiac sympatheticâ(SNS) and parasympathetic nervous system (PNS) activity parameters in healthy patients aged 0.5 to 20 years. A second aim was to determine potential sex differences.
Methods and Results
Five studies covering the 0.5â to 20âyear age range provided impedanceâ and electrocardiography recordings from which heart rate, different PNSâparameters (eg, respiratory sinus arrhythmia) and an SNSâparameter (preâejection period) were collected. Age trends were computed in the mean values across 12 ageâbins and in the ageâspecific variances. Age was associated with changes in mean and variance of all parameters. PNSâactivity followed a cubic trend, with an exponential increase from infancy, a plateau phase during middle childhood, followed by a decrease to adolescence. SNSâactivity showed a more linear trend, with a gradual decrease from infancy to adolescence. Boys had higher SNSâactivity at ages 11 to 15 years, while PNSâactivity was higher at 5 and 11 to 12 years with the plateau level reached earlier in girls. Interindividual variation was high at all ages. Variance was reasonably stable for SNSâ and the logâtransformed PNSâparameters.
Conclusions
Cardiac PNSâ and SNSâactivity in childhood follows different maturational trajectories. Whereas PNSâactivity shows a cubic trend with a plateau phase during middle childhood, SNSâactivity shows a linear decrease from 0.5 to 20 years. Despite the large samples used, clinical use of the sexâspecific centile and percentile normative values is modest in view of the large individual differences, even within narrow age bands.National Institute of Diabetes and Digestive and Kidney Diseases; the Netherlands Organization for Scientific Research; National Initiative for Brain and Cognition Research; European Commission under the 7th Framework Health Program with Grant; The Netherlands Organization for Health Research and Development (ZonMw); The Dutch Heart Foundatio
Human gene copy number variation and infectious disease
Variability in the susceptibility to infectious disease and its clinical manifestation can be determined by variation in the environment and by genetic variation in the pathogen and the host. Despite several successes based on candidate gene studies, defining the host variation affecting infectious disease has not been as successful as for other multifactorial diseases. Both single nucleotide variation and copy number variation (CNV) of the host contribute to the host's susceptibility to infectious disease. In this review we focus on CNV, particularly on complex multiallelic CNV that is often not well characterised either directly by hybridisation methods or indirectly by analysis of genotypes and flanking single nucleotide variants. We summarise the well-known examples, such as α-globin deletion and susceptibility to severe malaria, as well as more recent controversies, such as the extensive CNV of the chemokine gene CCL3L1 and HIV infection. We discuss the potential biological mechanisms that could underly any genetic association and reflect on the extensive complexity and functional variation generated by a combination of CNV and sequence variation, as illustrated by the Fc gamma receptor genes FCGR3A, FCGR3B and FCGR2C. We also highlight some understudied areas that might prove fruitful areas for further research