444 research outputs found

    A comparison of the development of audiovisual integration in children with autism spectrum disorders and typically developing children

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    This study aimed to investigate the development of audiovisual integration in children with Autism Spectrum Disorder (ASD). Audiovisual integration was measured using the McGurk effect in children with ASD aged 7–16 years and typically developing children (control group) matched approximately for age, sex, nonverbal ability and verbal ability. Results showed that the children with ASD were delayed in visual accuracy and audiovisual integration compared to the control group. However, in the audiovisual integration measure, children with ASD appeared to ‘catch-up’ with their typically developing peers at the older age ranges. The suggestion that children with ASD show a deficit in audiovisual integration which diminishes with age has clinical implications for those assessing and treating these children

    “Losing the Phobia:” Understanding How HIV Pre-exposure Prophylaxis Facilitates Bridging the Serodivide Among Men Who Have Sex With Men

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    The use of HIV serostatus information has played a pivotal role in partner selection norms. A phenomenon known as serosorting is the practice of selecting a partner based on a perception that they are of the same HIV status in order to avoid transmission from one partner to the other. An understudied aspect of serosorting is that it has a divisive effect—one accepts or rejects a potential partner based on a singular characteristic, the partner's HIV status, and thus excludes all others. This division has been formally referred to as the HIV serodivide. In this study, we explored partner selection strategies among a group of HIV-negative, young men who have sex with men (n = 29) enrolled in a PrEP demonstration project in Northern California. We found that trends in serosorting were in fact shifting, and that a new and opposite phenomenon was emerging, something we labeled “seromixing” and that PrEP use played a part in why norms were changing. We present three orientations in this regard: (1) maintaining the phobia: in which men justified the continued vigilance and exclusion of people living with HIV as viable sex or romantic partners, (2) loosening/relaxation of phobia: among men who were reflecting on their stance on serosorting and its implications for future sexual and/or romantic partnerships, and (3) losing the phobia: among men letting go of serosorting practices and reducing sentiments of HIV-related stigma. The majority of participants spoke of changing or changed attitudes about intentionally accepting rather than rejecting a person living with HIV as a sex partner. For those who maintained strict serosorting practices, their understandings of HIV risk were not erased as a result of PrEP use. These overarching themes help explain how PrEP use is contributing to a closing of the HIV serodivide

    Hexamerization-enhanced CD20 antibody mediates complement-dependent cytotoxicity in serum genetically deficient in C9

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    We examined complement-dependent cytotoxicity (CDC) by hexamer formation-enhanced CD20 mAb Hx-7D8 of patient-derived chronic lymphocytic leukemia (CLL) cells that are relatively resistant to CDC. CDC was analyzed in normal human serum (NHS) and serum from an individual genetically deficient for C9. Hx-7D8 was able to kill up to 80% of CLL cells in complete absence of C9. We conclude that the narrow C5b-8 pores formed without C9 are sufficient for CDC due to efficient antibody-mediated hexamer formation. In the absence of C9, we observed transient intracellular increases of Ca2 + during CDC (as assessed with FLUO-4) that were extended in time. This suggests that small C5b-8 pores allow Ca2 + to enter the cell, while dissipation of the fluorescent signal accompanying cell disintegration is delayed. The Ca2 + signal is retained concomitantly with TOPRO-3 (viability dye) staining, thereby confirming that Ca2 + influx represents the most proximate mediator of cell death by CDC

    Serum uric acid distribution according to SLC22A12 W258X genotype in a cross-sectional study of a general Japanese population

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    <p>Abstract</p> <p>Background</p> <p>Although <it>SLC22A12 258X </it>allele was found among those with hypouricemia, it was unknown that serum uric acid distribution among those with <it>SLC22A12 258X </it>allele. This study examined serum uric acid (SUA) distribution according to <it>SLC22A12 </it>W258X genotype in a general Japanese population.</p> <p>Methods</p> <p>Subjects were 5,023 health checkup examinees (3,413 males and 1,610 females) aged 35 to 69 years with creatinine < 2.0 mg/dL, who were participants of a cohort study belonging to the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). <it>SLC22A12 </it>W258X was genotyped with a polymerase chain reaction with confronting two-pair primers.</p> <p>Results</p> <p>The genotype frequency was 4,793 for <it>WW</it>, 225 for <it>WX</it>, and 5 for <it>XX</it>, which was in Hardy-Weinberg equilibrium (p = 0.164) with <it>X </it>allele 0.023 (95% confidence interval [0.021-0.027]). Mean (range) SUA was 6.2 (2.1-11.4) mg/dL for <it>WW</it>, 3.9 (0.8-7.8) mg/dL for <it>WX</it>, and 0.8 (0.7-0.9) mg/dL for <it>XX </it>among males, and 4.5 (1.9-8.9) mg/dL, 3.3 (2.0-6.5) mg/dL, and 0.60 (0.5-0.7) mg/dL among females, respectively. Six individuals with SUA less than 1.0 mg/dL included two males with <it>XX </it>genotype, one male with <it>WX </it>genotype, and three females with <it>XX </it>genotype. Subjects with <it>WX </it>genotype were 14 (77.8%) of 18 males with a SUA of 1.0-2.9 mg/dL, and 28 (34.6%) of 81 females with the same range of SUA. The corresponding values were 131 (25.1%) of 522 males and 37 (3.5%) of 1,073 females for SUA 3.0-4.9 mg/dL, and 8 (0.4%) of 2,069 males and 5 (1.1%) of 429 females for SUA 5.0-6.9 mg/dL. The <it>X </it>allele effect for SUA less than 3 mg/dL was significantly (p < 0.001) higher in males (OR = 102.5, [33.9-309.8]) than in females (OR = 25.6 [14.4-45.3]).</p> <p>Conclusions</p> <p>Although <it>SLC22A12 </it>W258X was a determining genetic factor on SUA, SUA of those with <it>WX </it>genotype distributed widely from 0.8 mg/dL to 7.8 mg/dL. It indicated that other genetic traits and/or lifestyle affected SUA of those with <it>WX </it>genotype, as well as those with <it>WW </it>genotype.</p

    Coulomb Interactions between Cytoplasmic Electric Fields and Phosphorylated Messenger Proteins Optimize Information Flow in Cells

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    Normal cell function requires timely and accurate transmission of information from receptors on the cell membrane (CM) to the nucleus. Movement of messenger proteins in the cytoplasm is thought to be dependent on random walk. However, Brownian motion will disperse messenger proteins throughout the cytosol resulting in slow and highly variable transit times. We propose that a critical component of information transfer is an intracellular electric field generated by distribution of charge on the nuclear membrane (NM). While the latter has been demonstrated experimentally for decades, the role of the consequent electric field has been assumed to be minimal due to a Debye length of about 1 nanometer that results from screening by intracellular Cl- and K+. We propose inclusion of these inorganic ions in the Debye-Huckel equation is incorrect because nuclear pores allow transit through the membrane at a rate far faster than the time to thermodynamic equilibrium. In our model, only the charged, mobile messenger proteins contribute to the Debye length.Using this revised model and published data, we estimate the NM possesses a Debye-Huckel length of a few microns and find this is consistent with recent measurement using intracellular nano-voltmeters. We demonstrate the field will accelerate isolated messenger proteins toward the nucleus through Coulomb interactions with negative charges added by phosphorylation. We calculate transit times as short as 0.01 sec. When large numbers of phosphorylated messenger proteins are generated by increasing concentrations of extracellular ligands, we demonstrate they generate a self-screening environment that regionally attenuates the cytoplasmic field, slowing movement but permitting greater cross talk among pathways. Preliminary experimental results with phosphorylated RAF are consistent with model predictions.This work demonstrates that previously unrecognized Coulomb interactions between phosphorylated messenger proteins and intracellular electric fields will optimize information transfer from the CM to the NM in cells

    Effect of an antepartum Pap smear on the coverage of a cervical cancer screening programme: a population-based prospective study

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    BACKGROUND: Almost one-third of Norwegian women aged 25–69 years invited to have a Pap smear do not attend during the recommended period, and thus constitute a population with high-risk of cervical cancer (CC). Since the incidence of precancerous lesions of the cervix peak with occurrence of pregnancies within the same decade in women aged 25 to 35 years of age, antepartum care presents an opportunity to offer a Pap smear thereby increasing the coverage of the programme. The study objective was to describe the effect of the antepartum Pap smear on the coverage of a cytological CC screening programme. METHODS: Among 2 175 762 women resident in Norway in 31.12.1996, all women who gave birth in 1996–7 were identified from the Medical Birth Registry of Norway. Attendance to the cervical cancer screening was assessed by linkage to the Cytology Registry separately for the pregnant and non-pregnant women cohorts. The results were stratified by age, history of previous Pap smear and history of invitation to the CC screening programme. Logistic regression was used to estimate the relative probabilities of having a Pap smear adjusted for age, screening history, and time since invitation, for pregnant and non-pregnant women, respectively. RESULTS: 69% of the pregnant women had a Pap smear during one year of follow-up since beginning of the pregnancy with the majority taken during the antepartum period. Irrespectively of age or history of having a Pap smear, pregnant women were 4.3 times more likely to have a Pap smear during follow-up compared to non-pregnant women. 63.2% of the pregnant women had a smear as response to the invitation letter compared to 28.7% of the non-pregnant women, OR = 2.1 (95% CI 1.9 to 2.4). As an indication of "over-screening", 5397 pregnant women (57.8%) with a smear shortly before the start of follow-up also had a new Papsmear, compared to 83 023 (32.3%) in non-pregnant. CONCLUSION: Pap smear screening during pregnancy increases the coverage of the CC screening programme. The contribution of the antepartum Pap smear to "over-screening" exists but its effect is modest in countries where women on average become pregnant after the start of recommended age of screening

    Electrophysiological Evidence of Atypical Spatial Attention in Those with a High Level of Self-reported Autistic Traits

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    Selective attention is atypical in individuals with autism spectrum conditions. Evidence suggests this is also the case for those with high levels of autistic traits. Here we investigated the neural basis of spatial attention in those with high and low levels of self-reported autistic traits via analysis of ERP deflections associated with covert attention, target selection and distractor suppression (the N2pc, NT and PD). Larger N2pc and smaller PD amplitude was observed in those with high levels of autistic traits. These data provide neural evidence for differences in spatial attention, specifically, reduced distractor suppression in those with high levels of autistic traits, and may provide insight into the experience of perceptual overload often reported by individuals on the autism spectrum
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