Epilepsy in a large cohort of children diagnosed with attention deficit/hyperactivity disorders (ADHD)

PurposeThe knowledge about possible relationships between ADHD and epilepsy is largely based on small samples of ADHD patients and on cohorts with epilepsy. There is insufficient information about the clinical characteristics of epilepsy among children diagnosed with ADHD. The aim of this study was to investigate the prevalence and characteristics of epilepsy in a large, unselected cohort of children with ADHD.MethodsWe conducted a retrospective chart-review of children with ADHD who were evaluated in our clinic between the years 2000 and 2005. We compared age, sex, disorders of psychological development, cognitive level, pharmacological treatment for ADHD, initial response to treatment and ADHD subtype with and without epilepsy. In addition, we compared our data with data from a Norwegian study in a large general pediatric population.ResultsOf 607 children with ADHD (age 6–14 years; 82.4% males); 14 (2.3%) had a history of epilepsy, and 13 of these had active epilepsy. This is a higher occurrence than expected in the general pediatric population (0.5%). The majority of our patients had mild (an easily treated) epilepsy and they were more likely to be seizure free (79%) compared to the patients with epilepsy in general pediatric population. The ADHD patients with and without epilepsy did not differ regarding age, gender, disorders of psychological development, IQ level < 85 or ADHD subtype. The patients had been diagnosed with epilepsy on average 1.8 years before the ADHD assessment. All patients with epilepsy were treated with methylphenidate (MPH), and initial response to MPH was achieved in 85.7%.ConclusionThe epilepsy diagnosis preceded the ADHD diagnosis, and was found in a significantly higher rate than would be expected in the general pediatric population. The majority of patients had mild epilepsy and ADHD-Combined Inattentive/Hyperactive-Impulsive Subtype. All cases with epilepsy and ADHD were treated with MPH, with initial response achieved in 86%.     

Benefits of clinical criteria and high-throughput sequencing for diagnosing children with syndromic craniosynostosis

An accurate diagnosis of syndromic craniosynostosis (CS) is important for personalized treatment, surveillance, and genetic counselling. We describe detailed clinical criteria for syndromic CS and the distribution of genetic diagnoses within the cohort. The prospective registry of the Norwegian National Unit for Craniofacial Surgery was used to retrieve individuals with syndromic CS born between 1 January 2002 and 30 June 2019. All individuals were assessed by a clinical geneticist and classified using defined clinical criteria. A stepwise approach consisting of single-gene analysis, comparative genomic hybridization (aCGH), and exome-based high-throughput sequencing, first filtering for 72 genes associated with syndromic CS, followed by an extended trio-based panel of 1570 genes were offered to all syndromic CS cases. A total of 381 individuals were registered with CS, of whom 104 (27%) were clinically classified as syndromic CS. Using the single-gene analysis, aCGH, and custom-designed panel, a genetic diagnosis was confirmed in 73% of the individuals (n = 94). The diagnostic yield increased to 84% after adding the results from the extended trio-based panel. Common causes of syndromic CS were found in 53 individuals (56%), whereas 26 (28%) had other genetic syndromes, including 17 individuals with syndromes not commonly associated with CS. Only 15 individuals (16%) had negative genetic analyses. Using the defined combination of clinical criteria, we detected among the highest numbers of syndromic CS cases reported, confirmed by a high genetic diagnostic yield of 84%. The observed genetic heterogeneity encourages a broad genetic approach in diagnosing syndromic CS.Subject terms: Genetic testing, Genetics research, Diseases     

Experimental results on bioaccumulation of metals and organic contaminants from marine sediments

A test-system for the assessment of bioavailability and bioaccumulation of metals and organic contaminants in marine benthic organisms is described and results from studies where this system has been applied are assessed. Sediments tested were polluted harbour sediment (from Norway), and clean sediments spikes with metal containing weight materials for drilling muds. Contaminants that may bioaccumulate under relevant conditions are indicated. The test-system uses two species of ecological relevance (Nereis diversicolor and Hinia reticulata). Interspecies differences in bioaccumulation were found for several compounds, which show the importance of using species with different modes of living in such tests. Compared to other PAHs, pyrene was found to bioaccumulate to a high degree (BioAccumulation Ratio, BAR=213.5>sediment concentration ratio, SCR=97.4; bioaccumulation factor, organism dw. conc. to sediment dw. conc., BAF=1.02), which shows that extrapolating bioaccumulation results between different substances is difficult. When assessing bioavailability of specific compounds, it is most adequate to perform direct measurements on exposed organisms, such as the experiments described here. The high bioaccumulation of compounds such as pyrene and nickel may in some cases be attributed to manipulation of the sediments and (for pyrene) lack of subsequent aging, thereby overestimating bioavailability.     

Heterotrophic Archaea dominate sedimentary subsurface ecosystems off Peru

Studies of deeply buried, sedimentary microbial communities and associated biogeochemical processes during Ocean Drilling Program Leg 201 showed elevated prokaryotic cell numbers in sediment layers where methane is consumed anaerobically at the expense of sulfate. Here, we show that extractable archaeal rRNA, selecting only for active community members in these ecosystems, is dominated by sequences of uncultivated Archaea affiliated with the Marine Benthic Group B and the Miscellaneous Crenarchaeotal Group, whereas known methanotrophic Archaea are not detectable. Carbon flow reconstructions based on stable isotopic compositions of whole archaeal cells, intact archaeal membrane lipids, and other sedimentary carbon pools indicate that these Archaea assimilate sedimentary organic compounds other than methane even though methanotrophy accounts for a major fraction of carbon cycled in these ecosystems. Oxidation of methane by members of Marine Benthic Group B and the Miscellaneous Crenarchaeotal Group without assimilation of methane-carbon provides a plausible explanation. Maintenance energies of these subsurface communities appear to be orders of magnitude lower than minimum values known from laboratory observations, and ecosystem-level carbon budgets suggest that community turnover times are on the order of 100-2,000 years. Our study provides clues about the metabolic functionality of two cosmopolitan groups of uncultured Archaea.     

The antiarrhythmic peptide analog ZP123 prevents atrial conduction slowing during metabolic stress

OBJECTIVE: As atrial conduction slowing is important in the pathogenesis of atrial reentry arrhythmias, a drug that increases atrial conduction or prevents atrial conduction slowing could serve to prevent atrial reentry arrhythmias. In this study, we investigated whether the novel stable antiarrhythmic peptide analog, ZP123, was able to prevent atrial conduction slowing. METHODS: We examined the effect of ZP123 on metabolic stress-induced changes in conduction velocity (CV) and on dynamic CV restitution in isolated left atria from male Sprague-Dawley rats. We performed binding of ZP123 to a broad panel of 80 different cardiac and noncardiac ion channels and receptors and examined the effect of ZP123 on HERG channel conductance. RESULTS: ZP123 dose-dependently prevented metabolic stress-induced atrial CV slowing at doses ranging from 1 nM to 10 microM. ZP123 did not affect CV during physiological conditions nor did it affect dynamic CV restitution. ZP123 had no effect on atrial contractility. ZP123 showed no or low affinity binding to all ion channels and receptors examined. ZP123 had no effects on HERG channel activity in concentrations that affected atrial conduction. The concentration of ZP123 giving maximal effect on atrial conduction (100 nM) inhibited the outward K(+)-current by 2.7 +/- 0.1%. CONCLUSION: ZP123 has no effects on atrial conduction during physiological conditions, but it selectively prevents atrial conduction slowing during metabolic stress.