New Scope of the Document Although reports on cardiovascular screening efficacy have predominantly involved populations of adolescents and young adults participating in competitive athletics, the ...context of the present discussion is intentionally (and necessarily) much more expansive. ...it is underscored that the present report is not limited in scope to universal mass screening for athlete populations but importantly includes considerations for screening large, young, and truly general populations (school-aged, 12-25 years old, of both sexes) with respect to relevant logistical, ethical, legal, and societal issues (e.g., in the United States or other countries or communities of various sizes, in schools, or in regional or military populations).
We investigated the potential of magnetic resonance imaging (MRI) to track magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model.
Adult farm pigs (n=5) ...were subjected to closed-chest experimental MI. MR-MSCs (2.8 to 16x107 cells) were injected intramyocardially under x-ray fluoroscopy. MRIs were obtained on a 1.5T MR scanner to demonstrate the location of the MR-MSCs and were correlated with histology. Contrast-enhanced MRI demonstrated successful injection in the infarct and serial MSC tracking was demonstrated in two animals.
MRI tracking of MSCs is feasible and represents a preferred method for studying the engraftment of MSCs in MI.
Background. We assessed human immunodeficiency virus (HIV) antibody seroreversion among individuals initiating antiretroviral therapy (ART) during acute/early HIV infection and determined whether ...seroreversion was associated with loss of cytotoxic T lymphocyte responses. Methods. Subjects in a cohort with acute/early HIV infection (<12 months into infection) who initiated ART within 28 days after study entry and maintained HIV type 1 ribonucleic acid levels of ⩽500 copies/mL for >24 weeks were selected. Two clinically available second-generation enzyme immunoassays (EIAs) and a confirmatory Western blot were used to screen subjects for antibody reversion. Those with negative screening test results underwent additional antibody testing, including a third-generation EIA, and were assessed for cytotoxic T lymphocyte responses. Results. Of 87 subjects identified, 12 (14%) had negative antibody test results at the start of ART; all 12 had seroconversion, although 1 had seroconversion only on a third-generation EIA. Of the 87 subjects, 6 (7%) had seroreversion on at least 1 EIA antibody assay while receiving ART during a median follow-up of 90 weeks. The only clinical predictor of seroreversion was a low baseline “detuned” (less sensitive) antibody. Cytotoxic T lymphocyte responses to HIV Gag peptides were detected in 4 of 5 subjects with seroreversion who could be tested. All 5 who had seroreversion who stopped ART experienced virologic rebound and antibody evolution. Conclusions. HIV antibody seroconversion on second-generation EIA antibody tests may fail to occur when ART is initiated early. Seroreversion was not uncommon among subjects treated early, although cytotoxic T lymphocyte responses to HIV antigens remained detectable in most subjects. Antibody seroreversion did not indicate viral eradication. A third-generation EIA was the most sensitive test for HIV antibodies.
Abstract Objective The Brazilian Amazon region has selenium (Se)-rich soil, which is associated with higher Se levels in populations fed locally grown produce. Brazil nuts are a major source of ...dietary Se and are included with meals offered to children enrolled in public preschool in Macapá. The aim of this study was to examine Se intake and status of these children. Methods The Macapá group consisted of 41 children from a public preschool who received 15 to 30 g of Brazil nuts 3 d/wk. The control group included 88 children from the nearby city of Belém who did not receive Brazil nut–enriched meals. In both groups, school meals comprised ≥90% of the children's total food consumption. Selenium was assessed using hydride generation quartz tube atomic absorption spectroscopy in plasma, erythrocytes, nails, hair and urine. Dietary intakes (macronutrients and Se) were evaluated using the duplicate-portion method. Results Both groups received inadequate intakes of energy and macronutrients. Selenium intake was excessive in both groups (155.30 and 44.40 μg/d, in Macapá and Belém, respectively). Intake was potentially toxic in Macapá on days when Brazil nuts were added to meals. Although biomarkers of Se exposure exceeded reference levels in the Macapá group, no clinical symptoms of Se overload (selenosis) were observed. Conclusions The inclusion of Brazil nuts in school meals provided to children with already high dietary Se intakes increased Se levels and may result in an increased risk for toxicity. As selenosis is associated with some chronic diseases, we recommend continued monitoring of Se intake and status in this population.
Swift J1858.6–0814 is a recently discovered X-ray binary notable for extremely strong variability (by factors of >100 in soft X-rays) in its discovery state. We present the detection of five ...thermonuclear (Type I) X-ray bursts from Swift J1858.6–0814, implying that the compact object in the system is a neutron star (NS). Some of the bursts show photospheric radius expansion, so their peak flux can be used to estimate the distance to the system. The peak luminosity, and hence distance, can depend on several system parameters; for the most likely values, a high inclination and a helium atmosphere, D = 12.8+0.8−0.6 kpc, although systematic effects allow a conservative range of 9–18 kpc. Before one burst, we detect a QPO at 9.6 ± 0.5 mHz with a fractional rms amplitude of 2.2 ± 0.2 per cent (0.5–10 keV), likely due to marginally stable burning of helium; similar oscillations may be present before the other bursts but the light curves are not long enough to allow their detection. We also search for burst oscillations but do not detect any, with an upper limit in the best case of 15 per cent fractional amplitude (over 1–8 keV). Finally, we discuss the implications of the NS accretor and this distance on other inferences which have been made about the system. In particular, we find that Swift J1858.6–0814 was observed at super-Eddington luminosities at least during bright flares during the variable stage of its outburst.
The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 ppm (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in ...2001, and is over an order of magnitude more precise than the previous measurement for the negative muon. The result a(mu(-))=11 659 214(8)(3) x 10(-10) (0.7 ppm), where the first uncertainty is statistical and the second is systematic, is consistent with previous measurements of the anomaly for the positive and the negative muon. The average of the measurements of the muon anomaly is a(mu)(exp)=11 659 208(6) x 10(-10) (0.5 ppm).
In this large randomized trial involving patients undergoing cardiac surgery who were at moderate-to-high risk, the outcomes at 6 months show that a restrictive red-cell transfusion strategy was ...noninferior to a liberal strategy with respect to the composite outcome.
In a randomized trial, 5243 patients undergoing cardiac surgery were assigned to a restrictive or a liberal red-cell transfusion threshold. The restrictive threshold was noninferior to the liberal ...one for the composite outcome of death, myocardial infarction, stroke, or renal failure.
Selenoproteins play important roles in antioxidant mechanisms, and are thus hypothesised to have some involvement in the pathology of certain types of dementia. Mild cognitive impairment (MCI) and ...Alzheimer's disease (AD) are both thought to involve impaired biological activity of certain selenoproteins. Previously, supplementation with a selenium-rich Brazil nut (
Bertholletia excelsa
) has shown potential in reducing cognitive decline in MCI patients, and could prove to be a safe and effective nutritional approach early in the disease process to slow decline. Here, we have conducted a pilot study that examined the effects of a range of single nucleotide polymorphisms (SNPs) in genes encoding the selenoproteins glutathione peroxidase (
GPX1
) and selenoprotein P (
SEPP
) in response to selenium supplementation
via
dietary Brazil nuts, including selenium status, oxidative stress parameters and
GPX1
and
SEPP
gene expression. Our data suggest that
GPX1
Pro198Leu
rs1050450
genotypes may differentially affect the selenium status and GPx activity. Moreover,
rs7579
and
rs3877899
SNPs in
SEPP
gene, as well as
GPX1 rs1050450
genotypes can influence the expression of
GPX1
and
SEPP
mRNA in response to Brazil nuts intake. This small study gives cause for larger investigations into the role of these SNPs in both the selenium status and response to selenium dietary intake, especially in chronic degenerative conditions like MCI and AD.
Selenoproteins play important roles in antioxidant mechanisms, but it is hypothesised that single polymorphism nucleotides (SNPs) may affect their function.
IMPORTANCE Convergent biological, epidemiological, and clinical data identified urate elevation as a candidate strategy for slowing disability progression in Parkinson disease (PD). OBJECTIVE To ...determine the safety, tolerability, and urate-elevating capability of the urate precursor inosine in early PD and to assess its suitability and potential design features for a disease-modification trial. DESIGN, SETTING, AND PARTICIPANTS The Safety of Urate Elevation in PD (SURE-PD) study, a randomized, double-blind, placebo-controlled, dose-ranging trial of inosine, enrolled participants from 2009 to 2011 and followed them for up to 25 months at outpatient visits to 17 credentialed clinical study sites of the Parkinson Study Group across the United States. Seventy-five consenting adults (mean age, 62 years; 55% women) with early PD not yet requiring symptomatic treatment and a serum urate concentration less than 6 mg/dL (the approximate population median) were enrolled. INTERVENTIONS Participants were randomized to 1 of 3 treatment arms: placebo or inosine titrated to produce mild (6.1-7.0 mg/dL) or moderate (7.1-8.0 mg/dL) serum urate elevation using 500-mg capsules taken orally up to 2 capsules 3 times per day. They were followed for up to 24 months (median, 18 months) while receiving the study drug plus 1 washout month. MAIN OUTCOMES AND MEASURES The prespecified primary outcomes were absence of unacceptable serious adverse events (safety), continued treatment without adverse event requiring dose reduction (tolerability), and elevation of urate assessed serially in serum and once (at 3 months) in cerebrospinal fluid. RESULTS Serious adverse events (17), including infrequent cardiovascular events, occurred at the same or lower rates in the inosine groups relative to placebo. No participant developed gout and 3 receiving inosine developed symptomatic urolithiasis. Treatment was tolerated by 95% of participants at 6 months, and no participant withdrew because of an adverse event. Serum urate rose by 2.3 and 3.0 mg/dL in the 2 inosine groups (P < .001 for each) vs placebo, and cerebrospinal fluid urate level was greater in both inosine groups (P = .006 and <.001, respectively). Secondary analyses demonstrated nonfutility of inosine treatment for slowing disability. CONCLUSIONS AND RELEVANCE Inosine was generally safe, tolerable, and effective in raising serum and cerebrospinal fluid urate levels in early PD. The findings support advancing to more definitive development of inosine as a potential disease-modifying therapy for PD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00833690
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