Emotional modulation of the ability to inhibit a prepotent response during childhood.

The present study examined the bottom-up influence of emotional context on response inhibition, an issue that remains largely unstudied in children. Thus, 62 participants, aged from 6 to 13 years old, were assessed with three stop signal tasks: one with circles, one with neutral faces, and one with emotional faces (happy and sad). Results showed that emotional context altered response inhibition ability in childhood. However, no interaction between age and emotional influence on response inhibition was found. Positive emotions were recognized faster than negative emotions, but the valence did not have a significant influence on response inhibition abilities.

Domestic radon exposure and risk of childhood cancer: a prospective census-based cohort study

BACKGROUND: In contrast with established evidence linking high doses of ionizing radiation with childhood cancer, research on low-dose ionizing radiation and childhood cancer has produced inconsistent results. OBJECTIVE: We investigated the association between domestic radon exposure and childhood cancers, particularly leukemia and central nervous system (CNS) tumors. METHODS: We conducted a nationwide census-based cohort study including all children < 16 years of age living in Switzerland on 5 December 2000, the date of the 2000 census. Follow-up lasted until the date of diagnosis, death, emigration, a child's 16th birthday, or 31 December 2008. Domestic radon levels were estimated for each individual home address using a model developed and validated based on approximately 45,000 measurements taken throughout Switzerland. Data were analyzed with Cox proportional hazard models adjusted for child age, child sex, birth order, parents' socioeconomic status, environmental gamma radiation, and period effects. RESULTS: In total, 997 childhood cancer cases were included in the study. Compared with children exposed to a radon concentration below the median (< 77.7 Bq/m3), adjusted hazard ratios for children with exposure ≥ the 90th percentile (≥ 139.9 Bq/m3) were 0.93 (95% CI: 0.74, 1.16) for all cancers, 0.95 (95% CI: 0.63, 1.43) for all leukemias, 0.90 (95% CI: 0.56, 1.43) for acute lymphoblastic leukemia, and 1.05 (95% CI: 0.68, 1.61) for CNS tumors. CONCLUSIONS: We did not find evidence that domestic radon exposure is associated with childhood cancer, despite relatively high radon levels in Switzerland.

Ammonia toxicity to the brain.

Hyperammonemia can be caused by various acquired or inherited disorders such as urea cycle defects. The brain is much more susceptible to the deleterious effects of ammonium in childhood than in adulthood. Hyperammonemia provokes irreversible damage to the developing central nervous system: cortical atrophy, ventricular enlargement and demyelination lead to cognitive impairment, seizures and cerebral palsy. The mechanisms leading to these severe brain lesions are still not well understood, but recent studies show that ammonium exposure alters several amino acid pathways and neurotransmitter systems, cerebral energy metabolism, nitric oxide synthesis, oxidative stress and signal transduction pathways. All in all, at the cellular level, these are associated with alterations in neuronal differentiation and patterns of cell death. Recent advances in imaging techniques are increasing our understanding of these processes through detailed in vivo longitudinal analysis of neurobiochemical changes associated with hyperammonemia. Further, several potential neuroprotective strategies have been put forward recently, including the use of NMDA receptor antagonists, nitric oxide inhibitors, creatine, acetyl-L-carnitine, CNTF or inhibitors of MAPKs and glutamine synthetase. Magnetic resonance imaging and spectroscopy will ultimately be a powerful tool to measure the effects of these neuroprotective approaches.

In vitro assessment of the pulmonary toxicity and gastric availability of lead-rich particles from a lead recycling plant

Epidemiological studies in urban areas have linked increasing respiratory and cardiovascular pathologies with atmospheric particulate matter (PM) from anthropic activities. However, the biological fate of metal-rich PM industrial emissions in urban areas of developed countries remains understudied. Lead toxicity and bioaccessibility assessments were therefore performed on emissions from a lead recycling plant, using complementary chemical acellular tests and toxicological assays, as a function of PM size (PM(10-2.5), PM(2.5-1) and PM(1)) and origin (furnace, refining and channeled emissions). Process PM displayed differences in metal content, granulometry, and percentage of inhalable fraction as a function of their origin. Lead gastric bioaccessibility was relatively low (maximum 25%) versus previous studies; although, because of high total lead concentrations, significant metal quantities were solubilized in simulated gastrointestinal fluids. Regardless of origin, the finest PM(1) particles induced the most significant pro-inflammatory response in human bronchial epithelial cells. Moreover, this biological response correlated with pro-oxidant potential assay results, suggesting some biological predictive value for acellular tests. Pulmonary effects from lead-rich PM could be driven by thiol complexation with either lead ions or directly on the particulate surface. Finally, health concern of PM was discussed on the basis of pro-inflammatory effects, accellular test results, and PM size distribution.

Clustering of health behaviours in adult survivors of childhood cancer and the general population.

BACKGROUND: Little is known about engagement in multiple health behaviours in childhood cancer survivors. METHODS: Using latent class analysis, we identified health behaviour patterns in 835 adult survivors of childhood cancer (age 20-35 years) and 1670 age- and sex-matched controls from the general population. Behaviour groups were determined from replies to questions on smoking, drinking, cannabis use, sporting activities, diet, sun protection and skin examination. RESULTS: The model identified four health behaviour patterns: 'risk-avoidance', with a generally healthy behaviour; 'moderate drinking', with higher levels of sporting activities, but moderate alcohol-consumption; 'risk-taking', engaging in several risk behaviours; and 'smoking', smoking but not drinking. Similar proportions of survivors and controls fell into the 'risk-avoiding' (42% vs 44%) and the 'risk-taking' cluster (14% vs 12%), but more survivors were in the 'moderate drinking' (39% vs 28%) and fewer in the 'smoking' cluster (5% vs 16%). Determinants of health behaviour clusters were gender, migration background, income and therapy. CONCLUSION: A comparable proportion of childhood cancer survivors as in the general population engage in multiple health-compromising behaviours. Because of increased vulnerability of survivors, multiple risk behaviours should be addressed in targeted health interventions.

Late morbidity during childhood and adolescence in previously premature neonates after patent ductus arteriosus closure.

The health status of previously premature neonates after closure of a patent ductus arteriosus (PDA) was analyzed in childhood and adolescence. Physician questionnaires were used to study 180 hospital survivors among 210 consecutive premature neonates who underwent PDA closure between 1985 and 2005. Complete follow-up data were obtained for 129 patients (72%). During a median follow-up period of 7 years (range, 2-22 years), three late deaths (2.3%) had occurred. Only 45% of the patients were considered healthy. Morbidity included developmental delay (41.1%), pulmonary illness (12.4%), neurologic impairment (14.7%), hearing impairment (3.9%), gastrointestinal disease (3.1%), and thoracic deformity (1.2%). None of the adverse variables during the neonatal period (intraventricular hemorrhage, bradycardia apnea syndrome, bronchopulmonary dysplasia, pulmonary bleeding, hyaline membrane disease, artificial respiration time [continuous positive airway pressure + intubation], or necrotizing enterocolitis) statistically predicted respective system morbidity at the follow-up evaluation. Hyaline membrane disease (odds ratio, 2.5; p = 0.026) and longer hospitalization time (odds ratio, 1.2 days per 10 hospitalization days; p = 0.032) in the newborn period were significant predictors of an unhealthy outcome at the last follow-up evaluation. Survival until childhood after closure of a hemodynamically significant PDA in premature neonates is satisfactory. However, physical and neurodevelopmental co-morbidity persist for half of the patients, perhaps as a sequela of prematurity unrelated to ductus closure.

The Bcl-2/Bcl-XL inhibitor ABT-737 promotes death of retinoblastoma cancer cells.

Purpose: Retinoblastoma is a malignant tumor that usually develops in early childhood. During retinoblastoma spreading, RB1 gene inactivation is followed by additional genomic modifications which progressively lead to resistance of tumor cells to death. Drugs that act at downstream levels of death signaling pathways should therefore be interesting in killing retinoblastoma cells. ABT-737, a BH3 mimetic molecule effective at the mitochondrial level, has been shown to induce apoptosis in different human tumoral cell lines as well as in primary patient-derived cells, and in a mouse xenograph model. Methods: In this report, we analyzed the pro-death effect of ABT-737 on two human retinoblastoma cell lines, Y79 and WERI-Rb, as well as on the mouse photoreceptor cell line 661W. Results: We observed that ABT-737 was very effective as a single agent in inducing human WERI-Rb cells apoptosis without affecting the mouse 661W photoreceptor cells. However human Y79 cells were resistant to ABT-737, as a probable consequence of the absence of Bax. The high sensitivity of WERI-Rb to ABT-737 can be increased by downregulating Mcl-1 using the proteasome inhibitor MG-132. Preliminary analysis in primary mouse retinoblastoma tumoral cell lines predicts high sensitivity to ABT-737. Conclusion: Our data suggest that ABT-737 or related compounds could be a highly effective drug in the treatment of some retinoblastomas.

Non-traumatic spinal cord ischaemia in childhood - clinical manifestation, neuroimaging and outcome.

BACKGROUND: Spinal cord ischaemia is rare in childhood and information on clinical presentation and outcome is scarce. METHODS: This is a retrospective analysis of eight patients and 75 additional cases from the literature. Data search included: patient's age, primary manifestation, risk factors, neuroimaging and outcome. RESULTS: Five female and three male patients gave consent to participate. Mean age was 12.5 years (10-15 years). Six patients presented with paraplegia; this was preceded by pain in four. Brown Sequard syndrome and quadriparesis were the two others' presenting condition. Sensation levels were thoracolumbar in seven cases. Bladder dysfunction only or bladder and bowel dysfunction were reported in eight and five patients respectively. Time to maximal symptom manifestation was <12 h in 7/8. Risk factors included surgery, minor trauma, recent infection, and thrombophilia. Mean follow-up was 3.3 years (0.25-6.3 years). Three patients remained wheelchair-dependent and three patients were ambulatory without aid. Bladder function recovered fully in five children. Most affected aspects of quality of life were physical and mental well-being and self-perception. T2-weighted-MR images showed pencil-like hyperintensity (8/8) in sagittal and H-shaped or snake-eyes-like lesion (6/8) in axial views. Analyses of all 83 patients were in congruence with the above results of the study group. CONCLUSION: Spinal cord ischaemia in childhood presenting with pain, paraplegia, and bladder dysfunction has high morbidity concerning motor problems and quality of life. Acute arterial ischaemic event in children seems similar to adult events with respect to clinical presentation and, surprisingly, also in outcome.

Carbon and oxygen isotope study of hydrothermal carbonates in the zinc-lead deposits of the San Vicente district, central Peru: A quantitative modeling on mixing processes and CO2 degassing

Carbon and oxygen isotope studies of the host and gangue carbonates of Mississippi Valley-type zinc-lead deposits in the San Vicente District hosted in the Upper Triassic to Lower Jurassic dolostones of the Pucara basin (central Peru) were used to constrain models of the ore formation. A mixing model between an incoming hot saline slightly acidic radiogenic (Pb, Sr) fluid and the native formation water explains the overall isotopic variation (delta(13)C = - 11.5 to + 2.5 parts per thousand relative to PDB and delta(18)O = + 18.0 to + 24.3 parts per thousand relative to SMOW) of the carbonate generations. The dolomites formed during the main ore stage show a narrower range (delta(13)C = - 0.1 to + 1.7 parts per thousand and delta(18)O = + 18.7 to + 23.4 parts per thousand) which is explained by exchange between the mineralizing fluids and the host carbonates combined with changes in temperature and pressure. This model of fluid-rock interaction explains the pervasive alteration of the host dolomite I and precipitation of sphalerite I. The open-space filling hydrothermal white sparry dolomite and the coexisting sphalerite II formed by prolonged fluid-host dolomite interaction and limited CO2 degassing. Late void-filling dolomite III (or calcite) and the associated sphalerite III formed as the consequence of CO2 degassing and concomitant pH increase of a slightly acidic ore fluid. Widespread brecciation is associated to CO2 outgassing. Consequently, pressure variability plays a major role in the ore precipitation during the late hydrothermal events in San Vicente. The presence of native sulfur associated with extremely carbon-light calcites replacing evaporitic sulfates (e.g., delta(13)C = - 11.5 parts per thousand), altered native organic matter and heavier hydrothermal bitumen (from - 27.0 to - 23.0 parts per thousand delta(13)C) points to thermochemical reduction of sulfate and/or thiosulfate. The delta(13)C- and delta(18)O-values of the altered host dolostone and hydrothermal carbonates, and the carbon isotope composition of the associated organic matter show a strong regional homogeneity. These results coupled with the strong mineralogical and petrographic similarities of the different MVT occurrences perhaps reflects the fact that the mineralizing processes were similar in the whole San Vicente belt, suggesting the existence of a common regional mineralizing hydrothermal system with interconnected plumbing.

Improved statistical evaluation of group differences in connectomes by screening-filtering strategy with application to study maturation of brain connections between childhood and adolescence.

Detecting local differences between groups of connectomes is a great challenge in neuroimaging, because the large number of tests that have to be performed and the impact on multiplicity correction. Any available information should be exploited to increase the power of detecting true between-group effects. We present an adaptive strategy that exploits the data structure and the prior information concerning positive dependence between nodes and connections, without relying on strong assumptions. As a first step, we decompose the brain network, i.e., the connectome, into subnetworks and we apply a screening at the subnetwork level. The subnetworks are defined either according to prior knowledge or by applying a data driven algorithm. Given the results of the screening step, a filtering is performed to seek real differences at the node/connection level. The proposed strategy could be used to strongly control either the family-wise error rate or the false discovery rate. We show by means of different simulations the benefit of the proposed strategy, and we present a real application of comparing connectomes of preschool children and adolescents.

Fatal tolperisone poisoning: autopsy and toxicology findings in three suicide cases.

Tolperisone (Mydocalm) is a centrally acting muscle relaxant with few sedative side effects that is used for the treatment of chronic pain conditions. We describe three cases of suicidal tolperisone poisoning in three healthy young subjects in the years 2006, 2008 and 2009. In all cases, macroscopic and microscopic autopsy findings did not reveal the cause of death. Systematic toxicological analysis (STA) including immunological tests, screening for volatile substances and blood, urine and gastric content screening by GC-MS and HPLC-DAD demonstrated the presence of tolperisone in all cases. In addition to tolperisone, only the analgesics paracetamol (acetaminophen), ibuprofen and naproxen could be detected. The blood ethanol concentrations were all lower than 0.10 g/kg. Tolperisone was extracted by liquid-liquid extraction using n-chlorobutane as the extraction solvent. The quantification was performed by GC-NPD analysis of blood, urine and gastric content. Tolperisone concentrations of 7.0 mg/l, 14 mg/l and 19 mg/l were found in the blood of the deceased. In the absence of other autopsy findings, the deaths in these three cases were finally explained as a result of lethal tolperisone ingestion. To the best of our knowledge, these three cases are the first reported cases of suicidal tolperisone poisonings.