Characterizing individual differences in children and adolescents with autism spectrum disorder: a descriptive study.

Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by a higher prevalence in male than in female participants. Recent studies have hypothesized the presence of different phenotypes in male and female participants with ASD. The present study aims to assess possible sex differences in cognitive and adaptive functioning, symptomatology of ASD, and psychopathological comorbidities in a large sample of children and adolescents with ASD. Methods: The study included a total of 2,146 children and adolescents diagnosed with ASD, comprising 1785 boys (mean age 7.12 ± 3.69 years) and 361 girls (mean age 6.25 ± 3.30 years). The age of the participants ranged from 1.35 to 19.05 years (mean age 9.98 ± 3.64). The study sought to include all children and adolescents diagnosed with Autism or ASD. Results: Present results showed that girls with ASD had lower IQs than boys but similar adaptive functioning. The severity of symptoms of ASD was greater in boys than in girls, as were scores on psychopathological measures. With increasing age, boys with ASD showed greater impairment in social communication skills than girls and increased psychopathological comorbidities. Older girls showed fewer restricted and repetitive behaviors. Discussion: Exploring phenotypic differences in children and adolescents with ASD fosters an understanding of subtle diagnostic facets that may go unrecognized, allowing for increasingly individualized and tailored interventions.

Properties of Naked Silver Clusters with Up to 100 Atoms as Found with Embedded-Atom and Density-Functional Calculations.

The structural and energetic properties of small silver clusters Agn with n = 2-100 atoms are reported. For n = 2-100 the embedded atom model for the calculation of the total energy of a given structure in combination with the basin-hopping search strategy for an unbiased structure optimization has been used to identify the energies and structures of the three energetically lowest-lying isomers. These optimized structures for n = 2-11 were subsequently studied further through density-functional-theory calculations. These calculations provide additional information on the electronic properties of the clusters that is lacking in the embedded-atom calculations. Thereby, also quantities related to the catalytic performance of the clusters are studied. The calculated properties in comparison to other available theoretical and experimental data show a good agreement. Previously unidentified magic (i.e., particularly stable) clusters have been found for n>80. In order to obtain a more detailed understanding of the structural properties of the clusters, various descriptors are used. Thereby, the silver clusters are compared to other noble metals and show some similarities to both copper and nickel systems, and also growth patterns have been identified. All vibrational frequencies of all the clusters have been calculated for the first time, and here we focus on the highest and lowest frequencies. Structural effects on the calculated frequencies were considered.

Temperature-dependent contractility of rat tunica dartos muscle: Contribution of cold, menthol-sensitive TRPM8.

Tunica dartos smooth muscle (TDSM) lies beneath the scrotal skin, and its contraction leads to scrotum wrinkling upon cooling. However, neither the nature of TDSM cold-sensitivity nor the underlying molecular sensors are well understood. Here we have investigated the role of cold/menthol-sensitive TRPM8 channel in TDSM temperature-dependent contractility. The contraction of isolated male rat TDSM strips was studied by tensiometry. TRPM8 expression was assayed by RT-PCR and fluorescence immunochemistry. Isolated TDSM strips responded to cooling from 33 °C to 20 °C by enhancement of basal tension, and increase of the amplitude and duration of electric field stimulated (EFS) contractions. The effects of cold on basal tension, but not on EFS-contractions, could be 80% inhibited by TRPM8 blockers, capsazepine and BCTC [N-(4­tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide], and could be partially mimicked by menthol. RT-PCR and immunolabeling showed TRPM8 mRNA and protein expression in TDSM cells with protein labelling being predominantly localized to intracellular compartments. Chemical castration of male rats consequent to the treatment with androgen receptor blocker, flutamide, led to the abrogation of cold effects on TDSM basal tension, but not on EFS-contractions, and to the disappearance of TRPM8 protein expression. We conclude that TRPM8 is involved in the maintenance of basal cold-induced TDSM tonus, but not in sympathetic nerve-mediated contractility, by acting as endoplasmic reticulum Ca2+ release channel whose expression in TDSM cells requires the presence of a functional androgen receptor. Thus, TRPM8 plays a crucial role in scrotal thermoregulation which is important for maintaining normal spermatogenesis and male fertility.

A Digital Clinical Guideline Based on HL7 Arden Syntax for the Treatment of Children with Traumatic Brain Injury.

BACKGROUND: Intracranial hypertension is a serious complication accompanying the intensive care of children with traumatic brain injury. Intensive care of these patients is based on internationally accepted guidelines and their local editions. OBJECTIVE: The goal was to develop a software system for digital implementation of the clinical protocol for the treatment of intracranial hypertension in children, based on HL7 Arden Syntax clinical decision support. METHODS: Arden Syntax, an HL7 medical knowledge representation and processing standard, was used to develop a digital version of the local guideline. RESULTS: Comparison of 37 patients given conventional treatment with a second group of 84 patients treated with the digital clinical guideline yielded statistically significant differences. CONCLUSION: The digital clinical guideline system undoubtedly improves the doctor's awareness of the patient's existing condition and potential complications of intracranial hypertension.

Cerebral Autoregulation Monitoring and Online Arden Syntax Clinical Decision Support for the Treatment of Intracranial Hypertension in Children with Traumatic Brain Injury.

BACKGROUND: Intracranial hypertension is a serious complication in the intensive care of children with severe traumatic brain injury (STBI). OBJECTIVE: The goal was to create a computer system for simultaneous neuromonitoring of cerebral parameters and Arden-Syntax-based clinical decision support (CDS) in children with STBI undergoing intensive care treatment. METHODS: Intensive care of these patients is based on internationally accepted guidelines. Arden Syntax, which is an HL7 medical knowledge representation and processing standard for CDS systems, was used to develop digital algorithms for these guidelines. RESULTS: Comparison of a group of 37 conventionally treated patients with a second group (84 patients) monitored and treated with the combined CDS system yielded statistically significant differences. CONCLUSION: A combination of cerebral autoregulation monitoring with Arden-Syntax-based CDS in accordance with guidelines for the treatment of intracranial hypertension in children with STBI provides markedly better treatment outcomes. It opens up new options for the use of standards to formalize and process medical knowledge in neuromonitoring.

Temperature and isomeric effects in nanoclusters.

The canonical thermodynamics of clusters is determined quantum mechanically in the general case of multiple minima of the potential energy surface (PES) using the superposition approximation. As an illustration of the consequences of our approach, we study in detail the thermodynamic properties of CuN clusters with N from 2 to 150 as a function of cluster size, temperature, and number of isomers. Thereby, for instance, solid-solid transition temperatures for several cluster sizes are determined. We show that the cluster vibrations have a strong impact on the stability of the clusters and that this can be observed not only at medium and high temperatures but also at low temperatures and even at T = 0 K. Thus, including zero-point corrections can change the relative energetic ordering of different isomers. This isomeric effect results in an oscillatory dependence of the heat capacity on cluster size at moderate and high temperatures. Moreover, for the identification of magic clusters at non-vanishing temperature, the Helmholtz free energy is analyzed as a function of cluster size and temperature within a one-, two-, and three-minima model of the PES. Thereby, we demonstrate that the concept of magic clusters is strongly temperature dependent so that in several cases clusters change from being magic or non-magic at T = 0 K to be the opposite at non-vanishing temperature. We emphasize that all these effects are not specific for copper clusters alone but can also be observed in other metal or semiconductor nanoclusters.

Integral Homeostasis Index in a Decision Support System for the Assessment and Prediction of the Clinical Condition of Children with Severe Mechanical Trauma.

OBJECTIVE: Daily assessment of the acid-base balance (ABB) in blood is one of the important elements of multi-parameter patient monitoring at intensive care units (ICUs). The present work aims to determine the effectiveness and validity of the integral homeostasis index IHx calculated from ABB blood test data for the assessment and prognosis of children with critical traumatic conditions. METHODS: 345 patients were studied. IHx was calculated and the data were subjected to statistical evaluation. An Arden-Syntax-based clinical decision support (CDS) platform was used. One purpose of the study was to incorporate the platform into the ICU IT landscape of the hospital, and the second purpose was to develop a CDS module for the calculation of IHx and present the results in real time to the attending physician. RESULTS: Integral homeostasis index IHx calculations as well as their prompt assessment permit better and more rapid treatment of children with severe traumatic injury.

The development of episodic future thinking in middle childhood.

The ability to imagine future events (episodic future thinking-EFT) emerges in preschoolers and further improves during middle childhood and adolescence. In the present study, we focused on the possible cognitive factors that affect EFT and its development. We assessed the ability to mentally project forward in time of a large cohort of 135 6- to 11-year-old children through a task with minimal narrative demands (the Picture Book Trip task adapted from Atance and Meltzoff in Cogn Dev 20(3):341-361. doi:10.1016/j.cogdev.2005.05.001, 2005) in order to avoid potential linguistic effects on children's performance. The results showed that this task can be used to assess the development of EFT at least until the age of 8. Furthermore, EFT scores correlated with measures of phonological short-term and verbal working memory. These results support the possibility that cognitive factors such as working memory play a key role in EFT.

Alterations of the bone marrow stromal microenvironment in adult patients with acute myeloid and lymphoblastic leukemias before and after allogeneic hematopoietic stem cell transplantation.

Bone marrow (BM) derived adult multipotent mesenchymal stromal cells (MMSCs) and fibroblast colony-forming units (CFU-Fs) of 20 patients with acute myeloid leukemia (AML) and 15 patients with acute lymphoblastic leukemia (ALL) before and during 1 year after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) were studied. The growth characteristics of MMSCs of all patients before allo-HSCT were not altered; however, relative expression level (REL) of some genes in MMSCs, but not in CFU-Fs, from AML and ALL patients significantly changed. After allo-HSCT, CFU-F concentration and MMSC production were significantly decreased for 1 year; REL of several genes in MMSCs and CFU-F-derived colonies were also significantly downregulated. Thus, chemotherapy that was used for induction of remission did not impair the function of stromal precursors, but gene expression levels were altered. Allo-HSCT conditioning regimens significantly damaged MMSCs and CFU-Fs, and the effect lasted for at least 1 year.

Brief Report: Self-Based and Mechanical-Based Future Thinking in Children with Autism Spectrum Disorder.

This brief report is a partial replication of the study by Jackson and Atance (J Dev Disabil 14:40-45, 2008) assessing nonverbal Self-based and Mechanical-based future thinking (FT) in children with Autism Spectrum Disorder (ASD). In a first step, these tasks were administered to 30 children with ASD. The two Self-based tasks were then modified as a verbal component could not be completely ruled out. Consequently, 77 children with ASD and 77 children with typical development received the modified Self-based FT tasks and the Mechanical-based FT tasks. We partially replicated the previous findings. Participants with ASD had impaired FT in both kinds of tasks and both groups performed better on tasks assessing Mechanical-based FT than Self-based FT. These results suggest that impairments of FT in ASD are not limited to Self-Projection.

Determination of the Average Native Background and the Light-Induced EPR Signals and their Variation in the Teeth Enamel Based on Large-Scale Survey of the Population.

The aim of the study is to determine the average intensity and variation of the native background signal amplitude (NSA) and of the solar light-induced signal amplitude (LSA) in electron paramagnetic resonance (EPR) spectra of tooth enamel for different kinds of teeth and different groups of people. These values are necessary for determination of the intensity of the radiation-induced signal amplitude (RSA) by subtraction of the expected NSA and LSA from the total signal amplitude measured in L-band for in vivo EPR dosimetry. Variation of these signals should be taken into account when estimating the uncertainty of the estimated RSA. A new analysis of several hundred EPR spectra that were measured earlier at X-band in a large-scale examination of the population of the Central Russia was performed. Based on this analysis, the average values and the variation (standard deviation, SD) of the amplitude of the NSA for the teeth from different positions, as well as LSA in outer enamel of the front teeth for different population groups, were determined. To convert data acquired at X-band to values corresponding to the conditions of measurement at L-band, the experimental dependencies of the intensities of the RSA, LSA and NSA on the m.w. power, measured at both X and L-band, were analysed. For the two central upper incisors, which are mainly used in in vivo dosimetry, the mean LSA annual rate induced only in the outer side enamel and its variation were obtained as 10 ± 2 (SD = 8) mGy y-1, the same for X- and L-bands (results are presented as the mean ± error of mean). Mean NSA in enamel and its variation for the upper incisors was calculated at 2.0 ± 0.2 (SD = 0.5) Gy, relative to the calibrated RSA dose-response to gamma radiation measured under non-power saturation conditions at X-band. Assuming the same value for L-band under non-power saturating conditions, then for in vivo measurements at L-band at 25 mW (power saturation conditions), a mean NSA and its variation correspond to 4.0 ± 0.4 (SD = 1.0) Gy.

Analysis of mammographic diagnostic errors in breast clinic.

Mammography is the gold standard for detection of early breast cancer and it is still the only diagnostic tool which shows reduction of the mortality from that. Despite that, there is a high chance of false negatives that can lead to diagnostic errors resulting in delays of treatment and worsening of prognosis. The aim of this study is to analyze the rate of false negative in mammography and assess the source of diagnostic errors. Two radiologists have retrospectively evaluated 500 mammograms performed between January 2008 and December 2011 in Breast Imaging Clinic. 250 patients (Group A) had been operated for breast cancer and 250 patients (Group B) were healthy woman submitted to mammography according to the guideline for early detection of breast cancer. In Group A, 138 patients (55.2 %) were true missed cancer, 61 had minimal sign (24.4 %) and 53 were false negative (FN) (20.4 %). The source of errors amongst the FN were in 42 % of cases due to perception, in 15 % to interpretation, in 10 % to subtle/unusual lesion characteristics, in 9 % error for satisfaction of search, in 7 % to inherent limitations of mammography, in 4 % to poor technique and 13 % for inadequate clinical management. The diagnostic errors in breast clinic services are not negligible. The largest number of FN results from perception errors, misinterpretation and inadequate clinical management. These can be related to factors such as inattention, fatigue or lack of experience. To reduce it, it is necessary to have a dedicated multidisciplinary staff and adequate equipment and workloads.

Sequence-Dependent Structure/Function Relationships of Catalytic Peptide-Enabled Gold Nanoparticles Generated under Ambient Synthetic Conditions.

Peptide-enabled nanoparticle (NP) synthesis routes can create and/or assemble functional nanomaterials under environmentally friendly conditions, with properties dictated by complex interactions at the biotic/abiotic interface. Manipulation of this interface through sequence modification can provide the capability for material properties to be tailored to create enhanced materials for energy, catalysis, and sensing applications. Fully realizing the potential of these materials requires a comprehensive understanding of sequence-dependent structure/function relationships that is presently lacking. In this work, the atomic-scale structures of a series of peptide-capped Au NPs are determined using a combination of atomic pair distribution function analysis of high-energy X-ray diffraction data and advanced molecular dynamics (MD) simulations. The Au NPs produced with different peptide sequences exhibit varying degrees of catalytic activity for the exemplar reaction 4-nitrophenol reduction. The experimentally derived atomic-scale NP configurations reveal sequence-dependent differences in structural order at the NP surface. Replica exchange with solute-tempering MD simulations are then used to predict the morphology of the peptide overlayer on these Au NPs and identify factors determining the structure/catalytic properties relationship. We show that the amount of exposed Au surface, the underlying surface structural disorder, and the interaction strength of the peptide with the Au surface all influence catalytic performance. A simplified computational prediction of catalytic performance is developed that can potentially serve as a screening tool for future studies. Our approach provides a platform for broadening the analysis of catalytic peptide-enabled metallic NP systems, potentially allowing for the development of rational design rules for property enhancement.

Comparative analysis between radiation doses obtained by EPR dosimetry using tooth enamel and established analytical methods for the population of radioactively contaminated territories.

A comparative analysis of radiation doses determined by tooth enamel electron paramagnetic resonance (EPR) spectroscopy and by an acknowledged analytical method is performed for individual doses and for average doses in population of some settlements of the Bryansk region (Russia), which have been contaminated after the Chernobyl nuclear accident. The analysis is performed for doses in the range of 0-200 mGy for individuals and in the range of 0-50 mGy for the averaged populations. The method of orthogonal distance linear regression is used for the analysis. For both data sets the slopes of the regression line close to unity and the intercept close to zero are obtained, which indicates that doses determined by these two methods agree with each other. The root-mean-square difference between the results of EPR and analytical methods is estimated to be 35 mGy for individual doses and 15 mGy for averaged doses, which is consistent with uncertainty of these methods.

Learning by observation in children with autism spectrum disorder.

BACKGROUND: Observing another person performing a complex action accelerates the observer's acquisition of the same action and limits the time-consuming process of learning by trial and error. Learning by observation requires specific skills such as attending, imitating and understanding contingencies. Individuals with autism spectrum disorder (ASD) exhibit deficits in these skills. METHOD: The performance of 20 ASD children was compared with that of a group of typically developing (TD) children matched for chronological age (CA), IQ and gender on tasks of learning of a visuomotor sequence by observation or by trial and error. Acquiring the correct sequence involved three phases: a detection phase (DP), in which participants discovered the correct sequence and learned how to perform the task; an exercise phase (EP), in which they reproduced the sequence until performance was error free; and an automatization phase (AP), in which by repeating the error-free sequence they became accurate and speedy. RESULTS: In the DP, ASD children were impaired in detecting a sequence by trial and error only when the task was proposed as first, whereas they were as efficient as TD children in detecting a sequence by observation. In the EP, ASD children were as efficient as TD children. In the AP, ASD children were impaired in automatizing the sequence. Although the positive effect of learning by observation was evident, ASD children made a high number of imitative errors, indicating marked tendencies to hyperimitate. CONCLUSIONS: These findings demonstrate the imitative abilities of ASD children although the presence of imitative errors indicates an impairment in the control of imitative behaviours.

Complex modulation of Ca(v)3.1 T-type calcium channel by nickel.

Nickel is considered to be a selective blocker of low-voltage-activated T-type calcium channel. Recently, the Ni(2+)-binding site with critical histidine-191 (H191) within the extracellular IS3-IS4 domain of the most Ni(2+)-sensitive Cav3.2 T-channel isoform has been identified. All calcium channels are postulated to also have intrapore-binding site limiting maximal current carried by permeating divalent cations (PDC) and determining the blockade by non-permeating ones. However, the contribution of the two sites to the overall Ni(2+) effect and its dependence on PDC remain uncertain. Here we compared Ni(2+) action on the wild-type "Ni(2+)-insensitive" Cav3.1w/t channel and Cav3.1Q172H mutant having glutamine (Q) equivalent to H191 of Cav3.2 replaced by histidine. Each channel was expressed in Xenopus oocytes, and Ni(2+) blockade of Ca(2+), Sr(2+), or Ba(2+) currents was assessed by electrophysiology. Inhibition of Cav3.1w/t by Ni(2+) conformed to two sites binding. Ni(2+) binding with high-affinity site (IC50 = 0.03-3 µM depending on PDC) produced maximal inhibition of 20-30% and was voltage-dependent, consistent with its location within the channel's pore. Most of the inhibition (70-80%) was produced by Ni(2+) binding with low-affinity site (IC50 = 240-700 µM). Q172H-mutation mainly affected low-affinity binding (IC50 = 120-160 µM). The IC50 of Ni(2+) binding with both sites in the Cav3.1w/t and Cav3.1Q172H was differentially modulated by PDC, suggesting a varying degree of competition of Ca(2+), Sr(2+), or Ba(2+) with Ni(2+). We conclude that differential Ni(2+)-sensitivity of T-channel subtypes is determined only by H-containing external binding sites, which, in the absence of Ni(2+), may be occupied by PDC, influencing in turn the channel's permeation.

DNA adenine methyltransferase (Dam) controls the expression of the cytotoxic enterotoxin (act) gene of Aeromonas hydrophila via tRNA modifying enzyme-glucose-inhibited division protein (GidA).

Aeromonas hydrophila is both a human and animal pathogen, and the cytotoxic enterotoxin (Act) is a crucial virulence factor of this bacterium because of its associated hemolytic, cytotoxic, and enterotoxic activities. Previously, to define the role of some regulatory genes in modulating Act production, we showed that deletion of a glucose-inhibited division gene (gidA) encoding tRNA methylase reduced Act levels, while overproduction of DNA adenine methyltransferase (Dam) led to a concomitant increase in Act-associated biological activities of a diarrheal isolate SSU of A. hydrophila. Importantly, there are multiple GATC binding sites for Dam within an upstream sequence of the gidA gene and one such target site in the act gene upstream region. We showed the dam gene to be essential for the viability of A. hydrophila SSU, and, therefore, to better understand the interaction of the encoding genes, Dam and GidA, in act gene regulation, we constructed a gidA in-frame deletion mutant of Escherichia coli GM28 (dam(+)) and GM33 (∆dam) strains. We then tested the expressional activity of the act and gidA genes by using a promoterless pGlow-TOPO vector containing a reporter green fluorescent protein (GFP). Our data indicated that in GidA(+) strains of E. coli, constitutive methylation of the GATC site(s) by Dam negatively regulated act and gidA gene expression as measured by GFP production. However, in the ∆gidA strains, irrespective of the presence or absence of constitutively active Dam, we did not observe any alteration in the expression of the act gene signifying the role of GidA in positively regulating Act production. To determine the exact mechanism of how Dam and GidA influence Act, a real-time quantitative PCR (RT-qPCR) assay was performed. The analysis indicated an increase in gidA and act gene expression in the A. hydrophila Dam-overproducing strain, and these data matched with Act production in the E. coli GM28 strain. Thus, the extent of DNA methylation caused by constitutive versus overproduction of Dam, as well as possible conformation of DNA influence the expression of act and gidA genes in A. hydrophila SSU. Our results indicate that the act gene is under the control of both Dam and GidA modification methylases, and Dam regulates Act production via GidA.

Contrast-enhanced MR cholangiography (MRCP) with GD-EOB-DTPA in evaluating biliary complications after surgery.

PURPOSE: We assessed the usefulness of contrast-enhanced magnetic resonance cholangiography (CE-MRC) with liver-specific contrast agent in evaluating the biliary tree after hepatic surgery. MATERIALS AND METHODS: A total of 142 patients with suspected biliary complications after liver surgery underwent hepatobiliary MR before and after administration of gadolinium ethoxy benzylic diethylenetriamine pentaacetic acid (Gd-EOB-DTPA). Unenhanced MR cholangiopancreatography (MRCP) and postcontrast MRC were obtained in all patients. Blinded image evaluation and semiquantitative analysis comparing MRCP and CE-MRC were performed by two experienced radiologists. RESULTS: In all cases, optimal postcontrast visualisation of the biliary tract was obtained. In 22 patients, a postsurgical biliary complication was confirmed. MRCP detected 64% of lesions, but in 36% of cases, an alteration was only suspected but not clearly defined. CE-MRC allowed definite diagnosis in 100% of cases. CONCLUSIONS: Hepatobiliary-specific contrast agents allow for accurate and extensive study of biliary tract alterations, especially in assessing postsurgical complications.

Reverse Monte Carlo modeling of ion conducting network glasses: an evaluation based on molecular dynamics simulations.

We investigate the quality of structural models generated by the Reverse Monte Carlo (RMC) method in a typical application to glass systems. To this end we calculate diffraction data from a Li(2)O-SiO(2) molecular dynamics (MD) simulation and use it, in addition to minimal pair distances and coordination numbers of silicon (oxygen) to oxygen (silicon) ions, as input for RMC modeling. Then we compare partial radial distribution functions, coordination numbers, bond angles, and ring sizes predicted by the RMC models with those of the MD system. It is found that partial distribution functions and properties on small lengths scales, as distributions of coordination numbers and bond angles, are well reproduced by the RMC modeling. Properties in the medium-range order regime are, however, not well captured, as is demonstrated by comparison of ring size distributions. Due care therefore has to be exercised when extracting structural features from RMC models in this medium-range order regime. In particular we show that the occurrence of such features can be a mere consequence of the chosen starting configuration.