757 research outputs found

    Elevated glutamatergic compounds in pregenual anterior cingulate in pediatric autism spectrum disorder demonstrated by 1H MRS and 1H MRSI.

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    Recent research in autism spectrum disorder (ASD) has aroused interest in anterior cingulate cortex and in the neurometabolite glutamate. We report two studies of pregenual anterior cingulate cortex (pACC) in pediatric ASD. First, we acquired in vivo single-voxel proton magnetic resonance spectroscopy ((1)H MRS) in 8 children with ASD and 10 typically developing controls who were well matched for age, but with fewer males and higher IQ. In the ASD group in midline pACC, we found mean 17.7% elevation of glutamate + glutamine (Glx) (p<0.05) and 21.2% (p<0.001) decrement in creatine + phosphocreatine (Cr). We then performed a larger (26 subjects with ASD, 16 controls) follow-up study in samples now matched for age, gender, and IQ using proton magnetic resonance spectroscopic imaging ((1)H MRSI). Higher spatial resolution enabled bilateral pACC acquisition. Significant effects were restricted to right pACC where Glx (9.5%, p<0.05), Cr (6.7%, p<0.05), and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (10.2%, p<0.01) in the ASD sample were elevated above control. These two independent studies suggest hyperglutamatergia and other neurometabolic abnormalities in pACC in ASD, with possible right-lateralization. The hyperglutamatergic state may reflect an imbalance of excitation over inhibition in the brain as proposed in recent neurodevelopmental models of ASD

    Delayed presentation of acute ischemic strokes during the COVID-19 crisis

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    This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Background: The COVID-19 pandemic has disrupted established care paths worldwide. Patient awareness of the pandemic and executive limitations imposed on public life have changed the perception of when to seek care for acute conditions in some cases. We sought to study whether there is a delay in presentation for acute ischemic stroke patients in the first month of the pandemic in the US. Methods: The interval between last-known-well (LKW) time and presentation of 710 consecutive patients presenting with acute ischemic strokes to 12 stroke centers across the US were extracted from a prospectively maintained quality database. We analyzed the timing and severity of the presentation in the baseline period from February to March 2019 and compared results with the timeframe of February and March 2020. Results: There were 320 patients in the 2-month baseline period in 2019, there was a marked decrease in patients from February to March of 2020 (227 patients in February, and 163 patients in March). There was no difference in the severity of the presentation between groups and no difference in age between the baseline and the COVID period. The mean interval from LKW to the presentation was significantly longer in the COVID period (603±1035 min) compared with the baseline period (442±435 min, P<0.02). Conclusion: We present data supporting an association between public awareness and limitations imposed on public life during the COVID-19 pandemic in the US and a delay in presentation for acute ischemic stroke patients to a stroke center

    On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm

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    N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al

    A randomized trial of mail vs. telephone invitation to a community-based cardiovascular health awareness program for older family practice patients [ISRCTN61739603]

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    BACKGROUND: Family physicians can play an important role in encouraging patients to participate in community-based health promotion initiatives designed to supplement and enhance their in-office care. Our objectives were to determine effective approaches to invite older family practice patients to attend cardiovascular health awareness sessions in community pharmacies, and to assess the feasibility and acceptability of a program incorporating invitation by physicians and feedback to physicians. METHODS: We conducted a prospective randomized trial with 1 family physician practice and 5 community pharmacies in Dundas, Ontario. Regular patients 65 years or older (n = 235) were randomly allocated to invitation by mail or telephone to attend pharmacy cardiovascular health awareness sessions led by volunteer peer health educators. A health record review captured blood pressure status, monitoring and control. At the sessions, volunteers helped patients to measure blood pressure using in-store machines and a validated portable device (BPM-100), and recorded blood pressure readings and self-reported cardiovascular risk factors. We compared attendance rates in the mail and telephone invitation groups and explored factors potentially associated with attendance. RESULTS: The 119 patients invited by mail and 116 patients contacted by telephone had a mean age of 75.7 (SD, 6.4) years and 46.8% were male. Overall, 58.3% (137/235) of invitees attended a pharmacy cardiovascular health awareness session. Patients invited by telephone were more likely to attend than those invited by mail (72.3% vs. 44.0%, OR 3.3; 95%CI 1.9–5.7; p < 0.001). CONCLUSION: While the attendance in response to a telephone invitation was higher, response to a single letter was substantial. Attendance rates indicated considerable interest in community-based cardiovascular health promotion activities. A large-scale trial of a pharmacy cardiovascular health awareness program for older primary care patients is feasible

    New high-speed centre of mass method incorporating background subtraction for accurate determination of fluorescence lifetime

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    We demonstrate an implementation of a centre-of-mass method (CMM) incorporating background subtraction for use in multifocal fluorescence lifetime imaging microscopy to accurately determine fluorescence lifetime in live cell imaging using the Megaframe camera. The inclusion of background subtraction solves one of the major issues associated with centre-of-mass approaches, namely the sensitivity of the algorithm to background signal. The algorithm, which is predominantly implemented in hardware, provides real-time lifetime output and allows the user to effectively condense large amounts of photon data. Instead of requiring the transfer of thousands of photon arrival times, the lifetime is simply represented by one value which allows the system to collect data up to limit of pulse pile-up without any limitations on data transfer rates. In order to evaluate the performance of this new CMM algorithm with existing techniques (i.e. Rapid lifetime determination and Levenburg-Marquardt), we imaged live MCF-7 human breast carcinoma cells transiently transfected with FRET standards. We show that, it offers significant advantages in terms of lifetime accuracy and insensitivity to variability in dark count rate (DCR) between Megaframe camera pixels. Unlike other algorithms no prior knowledge of the expected lifetime is required to perform lifetime determination. The ability of this technique to provide real-time lifetime readout makes it extremely useful for a number of applications

    Shape abnormalities of caudate nucleus in schizotypal personality disorder

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    Previously, we reported abnormal volume and global shape in the caudate nucleus in schizotypal personality disorder (SPD). Here, we use a new shape measure which importantly permits local in addition to global shape analysis, as well as local correlations with behavioral measures
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