In recent years, evidence has been provided that individuals with dyslexia show alterations in the anatomy and function of the auditory cortex. Dyslexia is considered to be a learning disability that ...affects the development of music and language capacity. We set out to test adolescents and young adults with dyslexia and controls (N = 52) for their neurophysiological differences by investigating the auditory evoked P1–N1–P2 complex. In addition, we assessed their ability in Mandarin, in singing, their musical talent and their individual differences in elementary auditory skills. A discriminant analysis of magnetencephalography (MEG) revealed that individuals with dyslexia showed prolonged latencies in P1, N1, and P2 responses. A correlational analysis between MEG and behavioral variables revealed that Mandarin syllable tone recognition, singing ability and musical aptitude (AMMA) correlated with P1, N1, and P2 latencies, respectively, while Mandarin pronunciation was only associated with N1 latency. The main findings of this study indicate that the earlier P1, N1, and P2 latencies, the better is the singing, the musical aptitude, and the ability to link Mandarin syllable tones to their corresponding syllables. We suggest that this study provides additional evidence that dyslexia can be understood as an auditory and sensory processing deficit.
Background
Physicians “purchase” many health care services on behalf of patients yet remain largely unaware of the costs of these services. Electronic health record (EHR) cost displays may facilitate ...cost-conscious ordering of health services.
Objective
To determine whether displaying hospital lab and imaging order costs is associated with changes in the number and costs of orders placed.
Design
Quasi-experimental study.
Participants
All patients with inpatient or observation encounters across a multi-site health system from April 2013 to October 2015.
Intervention
Display of order costs, based on Medicare fee schedules, in the EHR for 1032 lab tests and 1329 imaging tests.
Main Measures
Outcomes for both lab and imaging orders were (1) whether an order was placed during a hospital encounter, (2) whether an order was placed on a given patient-day, (3) number of orders placed per patient-day, and (4) cost of orders placed per patient-day.
Key Results
During the lab and imaging study periods, there were 248,214 and 258,267 encounters, respectively. Cost display implementation was associated with a decreased odds of any lab or imaging being ordered during the encounter (lab adjusted odds ratio AOR = 0.97,
p
= .01; imaging AOR = 0.97,
p
< .001), a decreased odds of any lab or imaging being ordered on a given patient-day (lab AOR = 0.95,
p
< .001; imaging AOR = 0.97,
p
< .001), a decreased number of lab or imaging orders on patient-days with orders (lab adjusted count ratio = 0.93,
p
< .001; imaging adjusted count ratio = 0.98,
p
< .001), and a decreased cost of lab orders and increased cost of imaging orders on patient-days with orders (lab adjusted cost ratio = 0.93,
p
< .001; imaging adjusted cost ratio = 1.02,
p
= .003). Overall, the intervention was associated with an 8.5 and 1.7% reduction in lab and imaging costs per patient-day, respectively.
Conclusions
Displaying costs within EHR ordering screens was associated with decreases in the number and costs of lab and imaging orders.
Insulin is both a hormone regulating energy metabolism and a growth factor. We and others have shown that physiological doses of insulin initiate complex signals in primary human and mouse β-cells, ...but the functional significance of insulin's effects on this cell type remains unclear. In the present study, the role of insulin in β-cell apoptosis was examined. Exogenous insulin completely prevented apoptosis induced by serum withdrawal when given at picomolar or low nanomolar concentrations but not at higher concentrations, indicating that physiological concentrations of insulin are antiapoptotic and that insulin signaling is self-limiting in islets. Insulin treatment was associated with the nuclear localization of Pdx1 and the prosurvival effects of insulin were largely absent in islets 50% deficient in Pdx1, providing direct evidence that Pdx1 is a signaling target of insulin. Physiological levels of insulin did not increase Akt phosphorylation, and the protective effects of insulin were only partially altered in islets lacking 80% of normal Akt activity, suggesting the presence of additional insulin-regulated antiapoptotic pathways. Proteomic analysis of insulin-treated human islets revealed significant changes in multiple proteins. Bridge-1, a Pdx1-binding partner and regulator of β-cell survival, was increased significantly at low insulin doses. Together, these data suggest that insulin can act as a master regulator of islet survival by regulating Pdx1. diabetes pancreatic β-cells programmed cell death autocrine insulin feedback signaling maturity onset diabetes of the young
Autoantibodies to proteinase 3 (PR3) are involved in the pathogenesis of autoimmune-mediated vasculitis in Wegener granulomatosis (WG). To address the question how the autoantigen PR3 becomes a ...target of adaptive immunity, we investigated the effect of PR3 on immature dendritic cells (iDCs) in patients with WG, healthy blood donors, and patients with Crohn disease (CD), another granulomatous disease. PR3 induces phenotypic and functional maturation of a fraction of blood monocyte-derived iDCs. PR3-treated DCs express high levels of CD83, a DC-restricted marker of maturation, CD80 and CD86, and HLA-DR. Furthermore, the DCs become fully competent antigen-presenting cells and can induce stimulation of PR3-specific CD4+ T cells, which produce IFN-γ. PR3-maturated DCs derived from WG patients induce a higher IFN-γ response of PR3-specific CD4+ T cells compared with patients with CD and healthy controls. The maturation of DCs mediated through PR3 was inhibited by a serine protease inhibitor, by antibodies directed against the protease-activated receptor-2 (PAR-2), and by inhibition of phospholipase C, suggesting that the interactions of PR3 with PAR-2 are involved in the induction of DC maturation. Wegener autoantigen interacts with a “gateway” receptor (PAR-2) on iDCs in vitro triggering their maturation and licenses them for a T helper 1 (Th1)–type response potentially favoring granuloma formation in WG.
Wegener's granulomatosis (WG) is characterized by granulomatous lesions and vasculitic disease manifestations. Granulomatous lesions are found in the upper and lower respiratory tract (eg, ...granulomatous sinusitis, orbital masses, and pulmonary granuloma), whereas vasculitic manifestations occur frequently in lung (alveolar hemorrhage) and kidney (glomerulonephritis). Vasculitis is typically associated with antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3. WG has been traditionally associated with a poor outcome and increased mortality as documented by numerous studies; however, recent cohort studies report an improved outcome, probably a consequence of increased awareness leading to an earlier diagnosis, and to improved treatment strategies derived from evidence from controlled trials. Treatment regimens for WG, adapted to disease stage and activity, are reviewed and discussed in this article.
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a clear genetic component. While most SLE patients carry rare gene variants in lupus risk genes, little is known about ...their contribution to disease pathogenesis. Amongst them, SH2B3-a negative regulator of cytokine and growth factor receptor signaling-harbors rare coding variants in over 5% of SLE patients. Here, we show that unlike the variant found exclusively in healthy controls, SH2B3 rare variants found in lupus patients are predominantly hypomorphic alleles, failing to suppress IFNGR signaling via JAK2-STAT1. The generation of two mouse lines carrying patients' variants revealed that SH2B3 is important in limiting the number of immature and transitional B cells. Furthermore, hypomorphic SH2B3 was shown to impair the negative selection of immature/transitional self-reactive B cells and accelerate autoimmunity in sensitized mice, at least in part due to increased IL-4R signaling and BAFF-R expression. This work identifies a previously unappreciated role for SH2B3 in human B cell tolerance and lupus risk.
ABSTRACT Our current understanding of galaxy evolution still has many uncertainties associated with the details of the accretion, processing, and removal of gas across cosmic time. The next ...generation of radio telescopes will image the neutral hydrogen (H i) in galaxies over large volumes at high redshifts, which will provide key insights into these processes. We are conducting the COSMOS H i Large Extragalactic Survey (CHILES) with the Karl G. Jansky Very Large Array, which is the first survey to simultaneously observe H i from z = 0 to z ∼ 0.5. Here, we report the highest redshift H i 21 cm detection in emission to date of the luminous infrared galaxy COSMOS J100054.83+023126.2 at z = 0.376 with the first 178 hr of CHILES data. The total H i mass is (2.9 1.0) × 1010M and the spatial distribution is asymmetric and extends beyond the galaxy. While optically the galaxy looks undisturbed, the H i distribution suggests an interaction with a candidate companion. In addition, we present follow-up Large Millimeter Telescope CO observations that show it is rich in molecular hydrogen, with a range of possible masses of (1.8-9.9) × 1010M . This is the first study of the H i and CO in emission for a single galaxy beyond z ∼ 0.2.
A self-report measure of body image in female breast cancer survivors, the Body Image and Relationships Scale (BIRS), was developed to address attitudes about appearance, health, physical strength, ...sexuality, relationships, and social functioning following treatment.
The 32-item measure, generated by expert consensus and revised based on focus group feedback, was administered to 95 female breast cancer participants twice within 1 to 2 weeks. Test-retest reliability, internal consistency, and validity of the measure were assessed using standard-scale construction techniques. The structure of the proposed measure was evaluated using exploratory factor analysis. Associations of the resulting factors and other variables were assessed using extreme groups analyses.
The BIRS had satisfactory test-retest reliability and internal consistency. Principal axis factoring revealed three factors: (1) health and strength, (2) social barriers, and (3) appearance and sexuality. Correlations of the subscales with standardized measures of related constructs were significant and in the anticipated directions. Extreme groups analyses suggested associations between less physical activity and more impairment on factors 1 and 3, premenopausal status at first diagnosis and more impairment on factor 2, and younger age at the time of survey administration and more impairment on factor 3.
The proposed scale demonstrated satisfactory reliability and internal consistency. Factor analysis revealed three subscales with coherent item content and differential associations with measures of activity level, menopause status, and age. Observed relationships with other measures support convergent and divergent validity. Results suggest that the proposed scale is useful for clinical and research applications.
Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for ...EV-related publications and vesicular components are currently challenging.
We present an improved version of EVpedia, a public database for EVs research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools and a personalized function. EVpedia includes 6879 publications, 172 080 vesicular components from 263 high-throughput datasets, and has been accessed more than 65 000 times from more than 750 cities. In addition, about 350 members from 73 international research groups have participated in developing EVpedia. This free web-based database might serve as a useful resource to stimulate the emerging field of EV research.
The web site was implemented in PHP, Java, MySQL and Apache, and is freely available at http://evpedia.info.
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