Development and User Satisfaction of “Plan-It Commander,” a Serious Game for Children with ADHD

The need for engaging treatment approaches within mental health care has led to the application of gaming approaches to existing behavioral training programs (i.e., gamification). Because children with attention deficit/hyperactivity disorder (ADHD) tend to have fewer problems with concentration and engagement when playing digital games, applying game technologies and design approaches to complement treatment may be a useful means to engage this population in their treatment. Unfortunately, gamified training programs currently available for ADHD have been limited in their ability to demonstrate in-game behavior skills that generalize to daily life situations. Therefore, we developed a new serious game (called “Plan-It Commander”) that was specifically designed to promote behavioral learning and promotes strategy use in domains of daily life functioning such as time management, planning/organizing, and prosocial skills that are known to be problematic for children with ADHD. An interdisciplinary team contributed to the development of the game. The game's content and approach are based on psychological principles from the Self-Regulation Model, Social Cognitive Theory, and Learning Theory. In this article, game development and the scientific background of the behavioral approach are described, as well as results of a survey (n = 42) to gather user feedback on the first prototype of the game. The findings suggest that participants were satisfied with this game and provided the basis for further development and research to the game. Implications for developing serious games and applying user feedback in game development are discussed

The K2K SciBar Detector

A new near detector, SciBar, for the K2K long-baseline neutrino oscillation expe riment was installed to improve the measurement of neutrino energy spectrum and to study neutrino interactions in the energy region around 1 GeV. SciBar is a 'fully active' tracking detector with fine segmentation consisting of plastic scintillator bars. The detector was constructed in summer 2003 and is taking data since October 2003. The basic design and initial performance is presented.Comment: 7 pages, 4figures, Contributed to Proceedings of the 10th Vienna Conference on Instrumentation, Vienna, February 16-21, 200

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

XLMR in MRX families 29, 32, 33 and 38 results from the dup24 mutation in the ARX (Aristaless related homeobox) gene

BACKGROUND: X-linked mental retardation (XLMR) is the leading cause of mental retardation in males. Mutations in the ARX gene in Xp22.1 have been found in numerous families with both nonsyndromic and syndromic XLMR. The most frequent mutation in this gene is a 24 bp duplication in exon 2. Based on this fact, a panel of XLMR families linked to Xp22 was tested for this particular ARX mutation. METHODS: Genomic DNA from XLMR families linked to Xp22.1 was amplified for exon 2 in ARX using a Cy5 labeled primer pair. The resulting amplicons were sized using the ALFexpress automated sequencer. RESULTS: A panel of 11 families with X-linked mental retardation was screened for the ARX 24dup mutation. Four nonsyndromic XLMR families – MRX29, MRX32, MRX33 and MRX38 – were found to have this particular gene mutation. CONCLUSION: We have identified 4 additional XLMR families with the ARX dup24 mutation from a panel of 11 XLMR families linked to Xp22.1. This finding makes the ARX dup24 mutation the most common mutation in nonsyndromic XLMR families linked to Xp22.1. As this mutation can be readily tested for using an automated sequencer, screening should be considered for any male with nonsyndromic MR of unknown etiology

Intravenous leiomyomatosis of the uterus with extension to the right heart

A 42-year-old woman admitted with debilitation and engorgement both lower extremities. Transthoracic two-dimensional echocardiography, abdominal ultrasound and computerized tomography revealed a lobulated pelvic mass, a mass within right internal iliac vein, both common iliac vein, as well as the inferior vena cava, extending into the right atrium. In addition, echocardiography and abdominal ultrasound showed the tumor of right atrium and inferior vena cave has no stalk and has well-demarcated borders with the wall of right atrium and inferior vena cave. Hence, the presumptive diagnosis of IVL was made by echocardiography and abdominal ultrasound and the presumptive diagnosis of sarcoma with invasion in right internal iliac vein, both common iliac vein, the inferior vena cava, as well as the right atrium was made by multi-detector-row computerized tomography. The patient underwent a one-stage combined multidisciplinary thoraco-abdominal operation under general anaesthetic. Subsequently the pathologic report confirmed IVL

Adaptive Mutations in the JC Virus Protein Capsid Are Associated with Progressive Multifocal Leukoencephalopathy (PML)

PML is a progressive and mostly fatal demyelinating disease caused by JC virus infection and destruction of infected oligodendrocytes in multiple brain foci of susceptible individuals. While JC virus is highly prevalent in the human population, PML is a rare disease that exclusively afflicts only a small percentage of immunocompromised individuals including those affected by HIV (AIDS) or immunosuppressive drugs. Viral- and/or host-specific factors, and not simply immune status, must be at play to account for the very large discrepancy between viral prevalence and low disease incidence. Here, we show that several amino acids on the surface of the JC virus capsid protein VP1 display accelerated evolution in viral sequences isolated from PML patients but not in sequences isolated from healthy subjects. We provide strong evidence that at least some of these mutations are involved in binding of sialic acid, a known receptor for the JC virus. Using statistical methods of molecular evolution, we performed a comprehensive analysis of JC virus VP1 sequences isolated from 55 PML patients and 253 sequences isolated from the urine of healthy individuals and found that a subset of amino acids found exclusively among PML VP1 sequences is acquired via adaptive evolution. By modeling of the 3-D structure of the JC virus capsid, we showed that these residues are located within the sialic acid binding site, a JC virus receptor for cell infection. Finally, we go on to demonstrate the involvement of some of these sites in receptor binding by demonstrating a profound reduction in hemagglutination properties of viral-like particles made of the VP1 protein carrying these mutations. Collectively, these results suggest that a more virulent PML causing phenotype of JC virus is acquired via adaptive evolution that changes viral specificity for its cellular receptor(s)

O2-Filled Swimbladder Employs Monocarboxylate Transporters for the Generation of O2 by Lactate-Induced Root Effect Hemoglobin

The swimbladder volume is regulated by O2 transfer between the luminal space and the blood In the swimbladder, lactic acid generation by anaerobic glycolysis in the gas gland epithelial cells and its recycling through the rete mirabile bundles of countercurrent capillaries are essential for local blood acidification and oxygen liberation from hemoglobin by the “Root effect.” While O2 generation is critical for fish flotation, the molecular mechanism of the secretion and recycling of lactic acid in this critical process is not clear. To clarify molecules that are involved in the blood acidification and visualize the route of lactic acid movement, we analyzed the expression of 17 members of the H+/monocarboxylate transporter (MCT) family in the fugu genome and found that only MCT1b and MCT4b are highly expressed in the fugu swimbladder. Electrophysiological analyses demonstrated that MCT1b is a high-affinity lactate transporter whereas MCT4b is a low-affinity/high-conductance lactate transporter. Immunohistochemistry demonstrated that (i) MCT4b expresses in gas gland cells together with the glycolytic enzyme GAPDH at high level and mediate lactic acid secretion by gas gland cells, and (ii) MCT1b expresses in arterial, but not venous, capillary endothelial cells in rete mirabile and mediates recycling of lactic acid in the rete mirabile by solute-specific transcellular transport. These results clarified the mechanism of the blood acidification in the swimbladder by spatially organized two lactic acid transporters MCT4b and MCT1b

Search for astronomical neutrinos from blazar TXS 0506+056 in super-kamiokande

We report a search for astronomical neutrinos in the energy region from several GeV to TeV in the direction of the blazar TXS 0506+056 using the Super-Kamiokande detector following the detection of a 100 TeV neutrinos from the same location by the IceCube collaboration. Using Super-Kamiokande neutrino data across several data samples observed from 1996 April to 2018 February we have searched for both a total excess above known backgrounds across the entire period as well as localized excesses on smaller timescales in that interval. No significant excess nor significant variation in the observed event rate are found in the blazar direction. Upper limits are placed on the electron- and muon-neutrino fluxes at the 90% confidence level as 6.0 × 10−7 and 4.5 × 10−7–9.3 × 10−10 [erg cm−2 s−1], respectively

Molecular analysis of HBV genotypes and subgenotypes in the Central-East region of Tunisia

<p>Abstract</p> <p>Background</p> <p>In Tunisia, country of intermediate endemicity for Hepatitis B virus (HBV) infection, most molecular studies on the virus have been carried out in the North of the country and little is known about other regions. The aim of this study was to determine HBV genotype and subgenotypes in Central-East Tunisia. A total of 217 HBs antigen positive patients were enrolled and determination of genotype was investigated in 130 patients with detectable HBV DNA. HBV genotyping methods were: PCR-RFLP on the pre-S region, a PCR using type-specific primers in the S region (TSP-PCR) and partial sequencing in the pre-S region.</p> <p>Results</p> <p>Three genotypes (D, B and A) were detected by the PCR-RFLP method and two (D and A) with the TSP-PCR method, the concordance between the two methods was 93%. Sequencing and phylogenetic analysis of 32 strains, retrieved the same genotype (D and A) for samples with concordant results and genotype D for samples with discordant results. The sequences of discordant genotypes had a restriction site in the pre-S gene which led to erroneous result by the PCR-RFLP method. Thus, prevalence of genotype D and A was 96% and 4%, respectively. Phylogenetic analysis showed the predominance of two subgenotypes D1 (55%) and D7 (41%). Only one strain clustered with D3 subgenotype (3%).</p> <p>Conclusions</p> <p>Predominance of subgenotype D7 appears to occur in northern regions of Africa with transition to subgenotype D1 in the East of the continent. HBV genetic variability may lead to wrong results in rapid genotyping methods and sequence analysis is needed to clarify atypical results.</p

Cellular immunity in children with successful immunoprophylactic treatment for mother-to-child transmission of hepatitis B virus

Background: The administration of hepatitis B immunoglobulin followed by hepatitis B vaccine can result in a protective efficacy of almost 90% in mother-to-child transmission of hepatitis B virus (HBV). However, little is known about immunity against HBV infection in children after immunoprophylactic treatment. We tried to assess the association between T-cell responses and viremia in children after successful prophylactic treatment. Methods: Thirteen children and their 8 HBV carrier mothers (8 families), who were positive for human leukocyte antigen (HLA)-A24, were enrolled in this study. All of the 13 children received immunoprophylactic treatment and became negative for hepatitis B surface antigen (HBsAg) after birth. HBV-specific cytotoxic T lymphocyte (CTL) responses were evaluated using IFNγ - enzyme-linked immunosorbent spot (ELISPOT) and major histocompatibility complex class I peptide pentamer assays. Serum HBV DNA was measured by real-time PCR. Results: Significant HBV-specific T-cell responses were detected in 2 (15%) of the 13 children by ELISPOT. However, the frequency of HLA-A24-HBV-specific CTLs was very low in both HBV carrier mothers and children using pentamers. Of the 13 children, 4 (31%) were positive for serum HBV DNA. However, the levels of serum HBV DNA were 100 copies/ml or less. One of the 2 children in whom significant HBV-specific CTL responses were detectable was positive for serum HBV DNA. Conclusions: HBV core and polymerase-specific T-cell responses were detected and a low-dose viremia was observed in children after successful immunoprophylaxis treatment. Although the presence of viremia was not related to HBV-specific T-cell responses, CTLs might play a role in the control of HBV infection in children born to HBsAg-positive mothers after immunoprophylactic treatment. </p