Perception in attention deficit hyperactivity disorder

A large body of research demonstrated that individuals with attention deficit hyperactivity disorder (ADHD) suffer from various neuropsychological deficits. In contrast, less is known and only divergent evidence exists on perceptual functions of individuals with ADHD. This is problematic as neuropsychological and perceptual functions are closely interrelated and are often difficult to disentangle in behavioral assessments. This study presents the conduct and results of a systematic literature review on perceptual functions in children and adults with ADHD. This review considers studies using psychophysical methods (objective measurements) and self- and informant reports (subjective measurements). Results indicate that individuals with ADHD have altered perceptual functions in various domains as compared to typically developing individuals. Increased perceptual functions in individuals with ADHD were found with regard to olfactory detection thresholds, whereas reduced perceptual functions were evident for aspects of visual and speech perception. Moreover, individuals with ADHD were found to experience discomfort to sensory stimuli at a lower level than typically developing individuals. Alterations of perceptual functions in individuals with ADHD were shown to be moderated by various factors, such as pharmacological treatment, cognitive functions, and symptom severity. We conclude by giving implications for daily life functioning and clinical practice.     

Chemical speciation of some heavy metals and human health risk assessment in soil around two municipal dumpsites in Sagamu,Ogun state,Nigeria

Environmental and health risk posed by heavy metals from municipal landfill cannot be over emphasized. However, the toxicity and fate of metal in the soil is dependent on its chemical form and therefore quantification of the different forms of metal is more meaningful than the estimation of its total concentration. This study investigated the chemical form and potential hazards of heavy metal pollution at two municipal landfills in Sagamu, Ogun state, Nigeria. Soil samples were collected around the landfills and chemical form of Cu, Zn, Cd, Pb, and Fe were studied, using the Tessier Five-step sequential chemical extraction procedure. The results showed that Cu and Fe were speciated into residual fractions with averages of 23.9 and 31.3% respectively, while Cd and Zn were associated with Carbonate fractions with respective averages of 20.3 and 20.6%. The order of mobility and bioavailability of these metals are: Cd > Pb > Cu > Zn > Fe. A comparison of the result of total extractible metals with standard set by USEPA reveals that Cd and Cu level in the dumpsite soils are far above the critical permissible limit of 3.0 and 250 mg kg^?1, respectively which potent a health risk. Assessment of soil pollution level using geoaccumulation index (I_geo) revealed that the landfill was extremely polluted by Cd (I_geo > 5). Pearson correlation and principal component analysis showed that there were no significant correlations (p < 0.05) among all the metals, suggesting that they are all from different anthropogenic sources. The cancer risk ranged from 1.36E?01 to 2.18E?04 and 5.82E?01 to 9.35E?04 for Children and Adult respectively. The level of cancer risk falls above the threshold values (10^?4–10^?6) which US Environmental Protection Agency considered as unacceptable risk. Based on the above findings, it was suggested that environmental management policy should be implemented to decrease the environmental risks.     

Structure and Function of CinD (YtjD) of Lactococcus lactis,a Copper-Induced Nitroreductase Involved in Defense against Oxidative Stress

In Lactococcus lactis IL1403, 14 genes are under the control of the copper-inducible CopR repressor. This so-called CopR regulon encompasses the CopR regulator, two putative CPx-type copper ATPases, a copper chaperone, and 10 additional genes of unknown function. We addressed here the function of one of these genes, ytjD, which we renamed cinD (copper-induced nitroreductase). Copper, cadmium, and silver induced cinD in vivo, as shown by real-time quantitative PCR. A knockout mutant of cinD was more sensitive to oxidative stress exerted by 4-nitroquinoline-N-oxide and copper. Purified CinD is a flavoprotein and reduced 2,6-dichlorophenolindophenol and 4-nitroquinoline-N-oxide with k_cat values of 27 and 11 s⁻¹, respectively, using NADH as a reductant. CinD also exhibited significant catalase activity in vitro. The X-ray structure of CinD was resolved at 1.35 Å and resembles those of other nitroreductases. CinD is thus a nitroreductase which can protect L. lactis against oxidative stress that could be exerted by nitroaromatic compounds and copper.Lactococcus lactis IL1403 is a Gram-positive lactic acid bacterium which is used for the manufacture of food and dairy products but also for an increasing number of biotechnological applications. Given the economical importance of this microorganism, it is often used as a model for molecular studies. Its genome has been sequenced (4), and its proteome has been extensively characterized (11). When applied to industrial processes, this bacterium has to face various stress conditions, such as low pH, high temperature, osmotic shock, and metal stress (44). For instance, in traditional cheese making in Switzerland, L. lactis is exposed to copper released from the copper vats.Copper is an essential micronutrient for both prokaryotes and eukaryotes. The two oxidation states of copper, Cu⁺ and Cu²⁺, allow its participation in many important biological functions. More than 30 enzymes are known to use copper as a cofactor, such as superoxide dismutase (SOD), cytochrome c oxidase, or lysyl oxidase (20). The redox activity of copper can also lead to the generation of free radicals, which cause cellular damage (42, 43). Recently, alternative copper toxicity mechanisms have been demonstrated in bacteria in which copper interferes with the formation of catalytic iron-sulfur clusters (6, 22). Whatever the mechanism of copper toxicity, maintenance of copper homeostasis by controlling the uptake, accumulation, detoxification, and removal of copper is critical for living organisms.Copper homeostasis in L. lactis has not yet been investigated in great detail but appears to resemble the well-characterized copper homeostatic system of Enterococcus hirae (34). L. lactis possesses a copRZA operon, which provides copper resistance. It encodes the CopA copper export ATPase, the CopR copper-inducible repressor, and the CopZ copper chaperone (23). CopR regulates not only the copRZA operon but also an additional 11 genes. This so-called CopR regulon also includes copB, encoding a second putative copper ATPase; lctO, encoding lactate oxidase; and the ydiDE, yahCD-yaiAB, and ytjDBA operons of unknown function. Of all the genes and operons constituting the CopR regulon, the ytjDBA operon was most strongly induced by copper (23). Based on sequence comparison, the first gene of this operon, ytjD, encodes an oxygen-insensitive nitroreductase, which we renamed cinD for copper-induced nitroreductase.Nitroreductases are called oxygen insensitive when they can catalyze the two-electron reduction of nitro compounds in the presence of oxygen. Such enzymes are widespread in nature and are able to reduce a wide range of substrates, such as furazones, nitroaromatic compounds, flavins, and ferricyanide, using NADH or NADPH as the reductant. They are flavoproteins of 22 to 24 kDa and form homodimers with one flavin mononucleotide cofactor per monomer. Although oxygen-insensitive nitroreductases have been extensively studied, their in vivo function remains largely unknown. The closest relative of CinD, which has functionally been studied, is FRP of Vibrio harveyi, with 29% sequence identity to CinD. FRP is not a typical nitroreductase but appears to function as an NADH flavin oxidoreductase which provides reduced flavin to luciferase (19). The next closest relative of CinD, NfsA of Escherichia coli, with 23% sequence identity, exhibits the broad substrate specificity typical of most nitroreductases (48). The structure of this enzyme has been solved at a resolution of 1.7 Å (17). It closely resembles the structures of other enzymes which belong to the oxygen-insensitive nitroreductase family. NfsA has recently been shown to participate in the degradation of 2,4,6-trinitrotoluene (10). This suggests that an important function of nitroreductases could be the metabolism of xenobiotics.We investigated here the structure and function of CinD of L. lactis. CinD was induced by copper, cadmium, and silver and protected L. lactis from oxidative stress exerted by 4-nitroquinoline-N-oxide (NQO). The purified enzyme is a flavoprotein and exhibited nitroreductase activity on NQO and a variety of other substrates, using NADH as the reductant. CinD also possesses catalase activity and is thus able to defend cells against oxidative stress exerted by hydrogen peroxide, xenobiotics, or copper. The three-dimensional structure of CinD was resolved at a 1.35-Å resolution and exhibits a typical nitroreductase structure.     

Retinoic acid, GABA-ergic, and TGF-beta signaling systems are involved in human cleft palate fibroblast phenotype

During embryogenesis, a complex interplay between extracellular matrix (ECM) molecules, regulatory molecules, and growth factors mediates morphogenetic processes involved in palatogenesis. Transforming growth factor-beta (TGF-beta), retinoic acid (RA), and gamma-aminobutyric acid (GABA)ergic signaling systems are also potentially involved. Using [3H]glucosamine and [35S]methionine incorporation, anion exchange chromatography, semiquantitative radioactive RT-PCR, and a TGF-beta binding assay, we aimed to verify the presence of phenotypic differences between primary cultures of secondary palate (SP) fibroblasts from 2-year-old subjects with familial nonsyndromic cleft lip and/or palate (CLP-SP fibroblasts) and age-matched normal SP (N-SP) fibroblasts. The effects of RA--which, at pharmacologic doses, induces cleft palate in newborns of many species--were also studied. We found an altered ECM production in CLP-SP fibroblasts that synthesized and secreted more glycosaminoglycans (GAGs) and fibronectin (FN) compared with N-SP cells. In CLP-SP cells, TGF-beta3 mRNA expression and TGF-beta receptor number were higher and RA receptor-alpha (RARA) gene expression was increased. Moreover, we demonstrated for the first time that GABA receptor (GABRB3) mRNA expression was upregulated in human CLP-SP fibroblasts. In N-SP and CLP-SP fibroblasts, RA decreased GAG and FN secretion and increased TGF-beta3 mRNA expression but reduced the number of TGF-beta receptors. TGF-beta receptor type I mRNA expression was decreased, TGF-beta receptor type II was increased, and TGF-beta receptor type III was not affected. RA treatment increased RARA gene expression in both cell populations but upregulated GABRB3 mRNA expression only in N-SP cells. These results show that CLP-SP fibroblasts compared with N-SP fibroblasts exhibit an abnormal phenotype in vitro and respond differently to RA treatment, and suggest that altered crosstalk between RA, GABAergic, and TGF-beta signaling systems could be involved in human cleft palate fibroblast phenotype.     

In vitro time-dependent response of periodontal ligament to mechanical loading.

This study examined the time-dependent response of bovine periodontal ligament (PDL). Applying linear viscoelastic theory, the objective was 1) to examine the linearity of the PDL's response in terms of its scaling and superposition property and 2) to generate the phase lag-vs.-frequency spectrum graph. PDL specimens were tested under three separate straining conditions: 1) tension ramp tests conducted at different strain rates, 2) pulling step-straining to 0.3 in discrete tests and to 0.3 and 0.6 in one continuous run, and 3) tension-compression sinusoidal oscillations. To this effect, bar-shaped specimens of bovine roots that comprised portions of dentin, PDL tissue, and alveolar bone were produced and strained in a microtensile machine. The experimental data demonstrated that neither the scaling nor the superposition properties were verified and that the viscoelastic response of the PDL was nonlinear. The PDL's elastic response was essentially stiffening, and its viscous component was pseudoplastic. The tangent of the PDL's strain-stress phase lag was in the 0-0.1 range in the tensile direction and in the 0.35-0.45 range in the compressive direction. In line with other biological tissues, the phase lag was largely independent of frequency. By use of the data generated, a mathematical model is outlined that reproduces both the elastic stiffening and viscous thinning of the PDL's response.     

Female reproductive success in gynodioecious Thymus vulgaris: pollen versus nutrient limitation and pollinator foraging behaviour

Gynodioecy is a dimorphic breeding system in which female individuals coexist with hermaphroditic individuals in the same population. Females only contribute to the next generation via ovules, and many studies have shown that they are usually less attractive than hermaphrodites to pollinators. Several mechanisms have been proposed to explain how females manage to persist in populations despite these disadvantages. The ‘resource reallocation hypothesis’ (RRH) states that females channel resources not invested in pollen production and floral advertisement towards the production of more and/or larger seeds. We investigated pollination patterns and tested the RRH in a population of Thymus vulgaris. We measured flower display, flower size, nectar production, visitation rates, pollinator constancy and flower lifespan in the two morphs. In addition, we measured experimentally the effects of pollen and resource addition on female reproductive success (fruit set, seed set, seed weight) of the two morphs. Despite lower investment in floral advertisement, female individuals were no less attractive to pollinators than hermaphrodites on a per flower basis. Other measures of pollinator behaviour (number of flowers visited per plant, morph preference and morph constancy) also showed that pollinators did not discriminate against female flowers. In addition, stigma receptivity was longer in female flowers. Accordingly, and contrary to most studies on gynodioecious species, reproductive success of females was not pollen limited. Instead, seed production was pollen limited in hermaphrodites, suggesting low levels of cross‐pollination in hermaphrodites. Seed production was resource limited in hermaphrodites, but not in females, thus providing support for the RRH. © 2014 The Linnean Society of London, Botanical Journal of the Linnean Society, 2014, 175 , 395–408.     

Calibration Test of PET Scanners in a Multi-Centre Clinical Trial on Breast Cancer Therapy Monitoring Using 18F-FLT

A multi-centre trial using PET requires the analysis of images acquired on different systems We designed a multi-centre trial to estimate the value of 18F-FLT-PET to predict response to neoadjuvant chemotherapy in patients with newly diagnosed breast cancer. A calibration check of each PET-CT and of its peripheral devices was performed to evaluate the reliability of the results.

Material and Methods

11 centres were investigated. Dose calibrators were assessed by repeated measurements of a 68Ge certified source. The differences between the clocks associated with the dose calibrators and inherent to the PET systems were registered. The calibration of PET-CT was assessed with an homogeneous cylindrical phantom by comparing the activities per unit of volume calculated from the dose calibrator measurements with that measured on 15 Regions of Interest (ROIs) drawn on 15 consecutive slices of reconstructed filtered back-projection (FBP) images. Both repeatability of activity concentration based upon the 15 ROIs (ANOVA-test) and its accuracy were evaluated.

Results

There was no significant difference for dose calibrator measurements (median of difference −0.04%; min = −4.65%; max = +5.63%). Mismatches between the clocks were less than 2 min in all sites and thus did not require any correction, regarding the half life of 18F. For all the PET systems, ANOVA revealed no significant difference between the activity concentrations estimated from the 15 ROIs (median of difference −0.69%; min = −9.97%; max = +9.60%).

Conclusion

No major difference between the 11 centres with respect to calibration and cross-calibration was observed. The reliability of our 18F-FLT multi-centre clinical trial was therefore confirmed from the physical point of view. This type of procedure may be useful for any clinical trial involving different PET systems.