ADHD and cannabis use in young adults examined using fMRI of a Go/NoGo task

Children diagnosed with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for substance abuse. Response inhibition is a hallmark of ADHD, yet the combined effects of ADHD and regular substance use on neural networks associated with response inhibition are unknown. Task-based functional Magnetic Resonance Imaging (fMRI) data from young adults with childhood ADHD with (n?=?25) and without (n?=?25) cannabis use ≥ monthly in the past year were compared with a local normative comparison group (LNCG) with (n?=?11) and without (n?=?12) cannabis use. Go/NoGo behavioral and fMRI data were evaluated for main and interaction effects of ADHD diagnosis and cannabis use. ADHD participants made significantly more commission errors on NoGo trials than controls. ADHD participants also had less frontoparietal and frontostriatal activity, independent of cannabis use. No main effects of cannabis use on response inhibition or functional brain activation were observed. An interaction of ADHD diagnosis and cannabis use was found in the right hippocampus and cerebellar vermis, with increased recruitment of these regions in cannabis-using controls during correct response inhibition. ADHD participants had impaired response inhibition combined with less fronto-parietal/striatal activity, regardless of cannabis use history. Cannabis use did not impact behavioral response inhibition. Cannabis use was associated with hippocampal and cerebellar activation, areas rich in cannabinoid receptors, in LNCG but not ADHD participants. This may reflect recruitment of compensatory circuitry in cannabis using controls but not ADHD participants. Future studies targeting hippocampal and cerebellar-dependent function in these groups may provide further insight into how this circuitry is altered by ADHD and cannabis use.     

Recent Trends in the Prevalence of Crohn’s Disease and Ulcerative Colitis in a Commercially Insured US Population

Purpose

Most US inflammatory bowel disease (IBD) epidemiology studies conducted to date have sampled small, geographically restricted populations and have not examined time trends. The aim of our study was to determine the prevalence of Crohn’s disease (CD) and ulcerative colitis (UC) in a commercially insured US population and compare prevalences across sociodemographic characteristics and time.

Methods

Using claims data from approximately 12 million Americans, we performed three consecutive 2-year cross-sectional studies. Cases of CD and UC were identified using a previously described algorithm. Prevalence was estimated by dividing cases by individuals in the source population. Logistic regression was used to compare prevalences by region, age, and sex.

Results

In 2009, the prevalences of CD and UC in children were 58 [95 % confidence interval (CI) 55–60] and 34 (95 % CI 32–36), respectively. In adults, the respective prevalences were 241 (95 % CI 238–245) and 263 (95 % CI 260–266). Data analysis revealed that IBD prevalences have slightly increased over time. Based on census data, an estimated 1,171,000 Americans have IBD (565,000 CD and 593,000 UC).

Conclusions

Analysis of the epidemiological data revealed an increasing burden of IBD in recent years, which may be used to inform policy.     

PKC-betaII sensitizes cardiac myofilaments to Ca2+ by phosphorylating troponin I on threonine-144

Ventricular myocytes express Galphaq-coupled receptors that can mediate enhanced contractility by increasing the sensitivity of the contractile apparatus to Ca(2+). The precise mechanisms underlying this change have been difficult to define, in part because myofilament regulatory proteins contain multiple phosphorylation sites for protein kinase C (PKC), protein kinase A (PKA) and myosin light chain kinase (MLCK), with potentially opposing effects. MLCK increases whereas PKC and PKA have a strong tendency to decrease myofilament Ca(2+) sensitivity in myocardium. Here we show in mouse cardiac myocytes that PKC-betaII can increase Ca(2+) sensitivity of tension by a similar magnitude to MLCK but via a distinct mechanism. For PKC-betaII (32)P-incorporation occurred primarily into cardiac troponin I (cTnI) and functional effects were highly dependent upon mutations in phosphorylation sites of cTnI. Replacement of serines-23/24 (PKA sites) with alanine prevented cross-phosphorylation of these sites, reduced (32)P-incorporation into cTnI by half and resulted in myofilament Ca(2+) sensitization rather than desensitization in response to PKC-betaII. Replacement of three additional sites on cTnI, serines-43/45 and threonine-144, eliminated PKC-betaII-mediated Ca(2+) sensitization and the remaining (32)P-incorporation into cTnI. A preference for PKC-betaII phosphorylation of threonine-144 in the intact filament lattice was revealed by differential stable isotope labeling and supported by an analysis of peptide phosphorylation. The results suggest that threonine-144 within the critical inhibitory domain of cTnI represents a novel site of regulation of myofilament Ca(2+) sensitivity by PKC-betaII, with possible implications for chronically stressed or diseased hearts.     

Biomineralization of calcium disilicide in porous polycaprolactone scaffolds

The incorporation of CaSi(2) grains within a polycaprolactone (PCL) framework results in bioactive and biodegradable scaffolds which may be used in bone tissue regeneration. Porous PCL scaffolds were prepared via a combination of salt-leaching and microemulsion methods. To provide markedly different structural environments for the inorganic phase, calcium disilicide powder was either added to a mixed-composition porogen during a given scaffold preparation, or alternatively added to pre-formed scaffolds. Selective fluorescent labeling, scanning electron microscopy (SEM), and energy dispersive X-ray (EDX) analysis were employed to assess scaffold calcification in vitro. The process of CaSi(2)/PCL scaffold calcification under zero bias, during which calcium phosphate growth is significantly dependent on the structural degradation of CaSi(2) grains, has a similar mechanism as the calcium phosphate growth on bioactive glasses/ceramics. The biomineralization of these scaffolds is initiated solely by the silicide phase and can be accelerated by the degradation of the polymer matrix.     

Beta-catenin abnormalities and associated insulin-like growth factor overexpression are important in phyllodes tumours and fibroadenomas of the breast

The aim of this study was to assess the expression of IGF-I and IGF-II in phyllodes tumours and fibroadenomas and to see if there is any correlation between nuclear beta-catenin expression and IGF-I and IGF-II expression in these tumours. In a previous study, it has been shown that Wnt signalling is important in the pathogenesis of phyllodes tumours of the breast. Epithelial Wnt5a overexpression and stromal Wnt2 overexpression were associated with abnormal, nuclear localization of beta-catenin in the stromal cells of these tumours. However, not all tumours with beta-catenin accumulation showed Wnt overexpression. One other possible cause of beta-catenin accumulation is overexpression of insulin-like growth factors (IGFs), as both IGF-I and IGF-II have been shown to stabilize beta-catenin. In this study, 30 fibroadenomas of the breast were assessed for beta-catenin expression using immunohistochemistry and the results were compared with previous data from 119 phyllodes tumours. In situ hybridization was used to assess IGF-I and IGF-II expression in 23 phyllodes tumours and 16 fibroadenomas. Nineteen phyllodes tumours (83%) showed widespread overexpression of IGF-II and 5/23 (22%) showed widespread overexpression of IGF-I. IGF-I expression correlated with nuclear beta-catenin staining in phyllodes tumours. Malignant phyllodes tumours showed no or little IGF-I expression. There was a degree of nuclear beta-catenin expression in the stroma (weak in 33%, moderate in 27%, and strong in 40%) in all fibroadenomas and nuclear beta-catenin staining correlated with IGF-I overexpression. Extensive IGF-II overexpression was also found in the majority of fibroadenomas (12/16). These results support the hypothesis that IGF-I and IGF-II overexpression may be important in the pathogenesis of fibroepithelial neoplasms of the breast and that IGF-I overexpression is likely to be contributing to the nuclear beta-catenin localization observed in the tumours.     

An ERP study of age‐related differences in the central cost of interlimb coordination

The study investigated event‐related EEG potentials during concurrent performance of interlimb coordination and visual oddball tasks by younger and older adults. Coordination task difficulty was equated between age groups by allowing participants to perform the task at self‐determined frequencies. The amplitude of the P3b component of the event‐related potentials (ERPs) elicited by visual task targets showed a different pattern across midline sites (Fz, Cz, Pz) for younger and older adults. While younger adults showed a parietal maximum, P3b amplitudes in older adults did not differ across midline site, with lower amplitudes at central and parietal sites than younger adults but higher amplitude at the frontal site. Younger adults also had significantly shorter P3b latency than older adults. The results suggest that older adults may rely more on cognitive control of their movements than younger adults.     

The role of computed tomography in adult post-mortem examinations: an overview

Radiology has been a part of autopsy practice since just after the discovery of X-rays. Today it remains an important investigative tool although the radiological modalities utilized are changing. The role of post-mortem cross-sectional imaging is gaining acceptance across the world in both natural and unnatural death investigation. This symposium paper provides an overview of the history of the introduction of computed tomography into post-mortem practice, the areas where it is currently been used in practice and problems encountered in relation to its use.     

A genome-wide search for linkage to asthma phenotypes in the genetics of asthma international network families: evidence for a major susceptibility locus on chromosome 2p

Asthma is a complex disease and the intricate interplay between genetic and environmental factors underlies the overall phenotype of the disease. Families with at least two siblings with asthma were collected from Europe, Australia and the US. A genome scan using a set of 364 families with a panel of 396 microsatellite markers was conducted. Nonparametric linkage analyses were conducted for asthma and three asthma-related phenotypes: bronchial hyper-reactivity (BHR), strict definition of asthma and atopic asthma. Nine chromosomal regions with LOD scores greater than 1.5 were identified (chromosomes 1q, 2p, 3q, 4p, 4q, 6q, 12q, 20p and 21). Linkage refinement analysis was performed for three BHR loci by genotyping single nucleotide polymorphisms at an average marker density of 1 cM. The LOD scores increased to 3.07 at chromosome 4p and 4.58 at chromosome 2p, while the chromosome 6p locus did not refine. The LOD score at the chromosome 2p locus is highly significant on a genome-wide basis. The refined locus covers a region with a physical size of 12.2 Mb. Taken together, these results provide evidence for a major asthma susceptibility locus on chromosome 2p.     

Identification of in vivo-induced bacterial protein antigens during human infection with Salmonella enterica serovar Typhi

We applied an immunoscreening technique, in vivo-induced antigen technology (IVIAT), to identify immunogenic bacterial proteins expressed during human infection with Salmonella enterica serovar Typhi, the cause of typhoid fever. We were able to assign a functional classification to 25 of 35 proteins identified by IVIAT. Of these 25, the majority represent proteins with known or potential roles in the pathogenesis of S. enterica. These include proteins implicated in fimbrial structure and biogenesis, antimicrobial resistance, heavy metal transport, bacterial adhesion, and extracytoplasmic substrate trafficking as well as secreted hydrolases. The 10 remaining antigens represent proteins with unknown functions. Of the 35 identified antigens, four had no immunoreactivity when probed with control sera from individuals never exposed to serovar Typhi organisms; these four included PagC, TcfB, and two antigens of unknown function encoded by STY0860 and STY3683. PagC is a virulence factor known to be upregulated in vivo in S. enterica serovar Typhimurium infection of mice. TcfB is the major structural subunit of a fimbrial operon found in serovar Typhi with no homolog in serovar Typhimurium organisms. By examining differential immunoreactivities in acute- versus convalescent-phase human serum samples, we found specific anti-PagC and anti-TcfB immunoglobulin G responses in patients with serovar Typhi bacteremia. Serovar Typhi antigens identified by IVIAT warrant further evaluation for their contributions to pathogenesis, and they may have diagnostic, therapeutic, or preventive uses.