Hyperuricemia and non-dipping blood pressure

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The puzzle of metabolic effects of obstructive sleep apnoea in children

In obese children with obstructive sleep apnoea insulin resistance is common while lipids do not show a clear patter

Relationship between mild to moderate renal dysfunction and obstructive sleep apnea: Data from the European sleep apnea database

The relationship between severity of obstructive sleep apnea (OSA) and kidney function was investigated in the European Sleep Apnea Database (ESADA), where clinical, sleep, and biochemical data of patients studied for suspected OSA in 24 sleep centres of 17 European countries are stored. After excluding patients with missing data or extremely high/low creatinine values, data from 8112 subjects (2328 female) with creatinine values ranging between 0.5 and 2.0 mg% were analyzed. Estimated glomerular filtration rate (eGFR) was obtained with the Modified Diet in Renal Disease (MDRD) equation. Patients were subdivided into two groups: group 1 (n = 3709) studied by full polysomnography; group 2 (n = 4403) studied by nocturnal cardiorespiratory monitoring. Altogether, 8.5% subjects had an eGFR<60 ml/min/1.73m2. At univariate analysis, eGFR correlated to age, comorbidities and severity of OSA in both groups. At logistic regression analysis, risk factors for eGFR<60 were in group 1: diabetes, female gender, age, body mass index, and lowest nocturnal SaO2 (r2=0.086); in group 2: hypertension, female gender, age, and lowest nocturnal SaO2 (r2=0.087). In conclusion, as expected, comorbidities, female gender and advanced age are significant risk factors for low eGFR in subjects with OSA. While traditional severity measures of OSA (apnea/hypopnea index, oxygen desaturation index) did not contribute to low eGFR, more severe nocturnal hypoxia captured by lowest nocturnal SaO2 appeared as a significant predictor in this large patient cohort. The ESADA study is supported by ResMed and Philips Respironics

Far Infrared Variability of Sagittarius A*: 25.5 Hours of Monitoring with HerschelHerschel

Variable emission from Sgr~A*, the luminous counterpart to the super-massive black hole at the center of our Galaxy, arises from the innermost portions of the accretion flow. Better characterization of the variability is important for constraining models of the low-luminosity accretion mode powering Sgr~A*, and could further our ability to use variable emission as a probe of the strong gravitational potential in the vicinity of the $4\times10^{6}\mathrm{M}_{\odot}$ black hole. We use the \textit{Herschel} Spectral and Photometric Imaging Receiver (SPIRE) to monitor Sgr~A* at wavelengths that are difficult or impossible to observe from the ground. We find highly significant variations at 0.25, 0.35, and 0.5 mm, with temporal structure that is highly correlated across these wavelengths. While the variations correspond to $<$1% changes in the total intensity in the \textit{Herschel} beam containing Sgr~A*, comparison to independent, simultaneous observations at 0.85 mm strongly supports the reality of the variations. The lowest point in the light curves, $\sim$0.5 Jy below the time-averaged flux density, places a lower bound on the emission of Sgr~A* at 0.25 mm, the first such constraint on the THz portion of the SED. The variability on few hour timescales in the SPIRE light curves is similar to that seen in historical 1.3 mm data, where the longest time series is available, but the distribution of variations in the sub-mm do not show a tail of large-amplitude variations seen at 1.3 mm. Simultaneous X-ray photometry from XMM-Newton shows no significant variation within our observing period, which may explain the lack of very large variations if X-ray and submillimeter flares are correlated.Comment: Accepted for publication in Ap

An Inverse Compton Scattering Origin of X-ray Flares from Sgr A*

The X-ray and near-IR emission from Sgr A* is dominated by flaring, while a quiescent component dominates the emission at radio and sub-mm wavelengths. The spectral energy distribution of the quiescent emission from Sgr A* peaks at sub-mm wavelengths and is modeled as synchrotron radiation from a thermal population of electrons in the accretion flow, with electron temperatures ranging up to $\sim 5-20$\,MeV. Here we investigate the mechanism by which X-ray flare emission is produced through the interaction of the quiescent and flaring components of Sgr A*. The X-ray flare emission has been interpreted as inverse Compton, self-synchrotron-Compton, or synchrotron emission. We present results of simultaneous X-ray and near-IR observations and show evidence that X-ray peak flare emission lags behind near-IR flare emission with a time delay ranging from a few to tens of minutes. Our Inverse Compton scattering modeling places constraints on the electron density and temperature distributions of the accretion flow and on the locations where flares are produced. In the context of this model, the strong X-ray counterparts to near-IR flares arising from the inner disk should show no significant time delay, whereas near-IR flares in the outer disk should show a broadened and delayed X-ray flare.Comment: 22 pages, 6 figures, 2 tables, AJ (in press

Determinants of Sleepiness at Wheel and Missing Accidents in Patients With Obstructive Sleep Apnea

Study Objectives: Motor-vehicle crashes are frequent in untreated OSA patients but there is still uncertainty on prevalence as well as physiological or clinical determinants of sleepiness at the wheel (SW) in OSA patients. We assessed determinants of SW or sleepiness related near-miss car accident (NMA) in a group of non-professional drivers with OSA. Methods: A 237 consecutive, treatment-naïve PSG-diagnosed OSA patients (161 males, 53.1 ± 12.6 years) were enrolled. Self-reported SW was assessed by positive answer to the question, “Have you had episodes of falling asleep while driving or episodes of drowsiness at wheel that could interfere with your driving skill in the last year?” Occurrence of NMA in the last 3 years was also individually recorded. Habitual self-reported average sleep time was collected. Results: SW was found in 41.3% of patients but one-quarter of patients with SW did not report excessive daytime sleepiness. Predictors of SW were the following subjective factors: Epworth sleepiness scale score (ESS-OR 1.26; IC 1.1–1.4; p &lt; 0.0001), depressive symptoms (BDI-OR 1.2; IC 1.06–1.18; p &lt; 0.0001) and level of risk exposure (annual mileage-OR 1.9; IC 1.15–3.1; p = 0.007). NMAs were reported by 9.7% of patients, but more frequently by SW+ than SW– (22.4% vs. 0.7%; χ2 31, p &lt; 0.0001). The occurrence of NMAs was significantly associated to ESS, BDI, habitual sleep duration and ODI (R2 = 0.41). Conclusion: SW is not predicted by severity of OSA. Evaluation of risk exposure, assessment of depressive symptoms, and reported NMA should be included in the clinical evaluation, particularly in patients with reduced habitual sleep time and severe nocturnal hypoxia

Modelling the black hole silhouette in Sgr A* with ion tori

We calculate the "observed at infinity" image and spectrum of the accretion structure in Sgr A*, by modelling it as an optically thin, constant angular momentum ion torus in hydrodynamic equilibrium. The physics we consider includes a two-temperature plasma, a toroidal magnetic field, as well as radiative cooling by bremsstrahlung, synchrotron and inverse Compton processes. Our relativistic model has the virtue of being fully analytic and very simple, depending only on eight tunable parameters: the black hole spin and the inclination of the spin axis to our line of sight, the torus angular momentum, the polytropic index, the magnetic to total pressure ratio, the central values of density and electron temperature and the ratio of electron to ion temperatures. The observed image and spectrum are calculated numerically using the ray-tracing code GYOTO. Our results demonstrate that the ion torus model is able to account for the main features of the accretion structure surrounding Sgr A*.Comment: 11 pages, 10 figures, submitted to A &

X-ray and Radio Variability of M31*, The Andromeda Galaxy Nuclear Supermassive Black Hole

We confirm our earlier tentative detection of M31* in X-rays and measure its light-curve and spectrum. Observations in 2004-2005 find M31* rather quiescent in the X-ray and radio. However, X-ray observations in 2006-2007 and radio observations in 2002 show M31* to be highly variable at times. A separate variable X-ray source is found near P1, the brighter of the two optical nuclei. The apparent angular Bondi radius of M31* is the largest of any black hole, and large enough to be well resolved with Chandra. The diffuse emission within this Bondi radius is found to have an X-ray temperature ~0.3 keV and density 0.1 cm-3, indistinguishable from the hot gas in the surrounding regions of the bulge given the statistics allowed by the current observations. The X-ray source at the location of M31* is consistent with a point source and a power law spectrum with energy slope 0.9+/-0.2. Our identification of this X-ray source with M31* is based solely on positional coincidence.Comment: 25 pages, 8 figures, submitted to Ap

Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?

LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular dystrophy. Up-regulation of LARGE has previously been proposed as a therapy for the secondary dystroglycanopathies: overexpression in cells compensates for defects in multiple dystroglycanopathy genes. Counterintuitively, LARGE overexpression in an FKRP-deficient mouse exacerbates pathology, suggesting that modulation of α-DG glycosylation requires further investigation. Here we demonstrate that transgenic expression of human LARGE (LARGE-LV5) in the LARGEmyd mouse restores α-DG glycosylation (with marked hyperglycosylation in muscle) and that this corrects both the muscle pathology and brain architecture. By quantitative analyses of LARGE transcripts we also here show that levels of transgenic and endogenous LARGE in the brains of transgenic animals are comparable, but that the transgene is markedly overexpressed in heart and particularly skeletal muscle (20–100 fold over endogenous). Our data suggest LARGE overexpression may only be deleterious under a forced regenerative context, such as that resulting from a reduction in FKRP: in the absence of such a defect we show that systemic expression of LARGE can indeed act therapeutically, and that even dramatic LARGE overexpression is well-tolerated in heart and skeletal muscle. Moreover, correction of LARGEmyd brain pathology with only moderate, near-physiological LARGE expression suggests a generous therapeutic window

Hepatitis B immunity in teenagers vaccinated as infants: an Italian 17-year follow-up study

AbstractWe assessed the persistence of hepatitis B surface antigen antibody (anti-HBs) and immune memory in a cohort of 571 teenagers vaccinated against hepatitis B as infants, 17 years earlier. Vaccinees were followed-up in 2003 and in 2010 (i.e. 10 years and 17 years after primary vaccination, respectively). When tested in 2003, 199 vaccinees (group A) had anti-HBs <10 mIU/mL and were boosted, 372 (group B) were not boosted because they had anti-HBs ≥10 mIU/mL (n = 344) or refused booster (n = 28) despite anti-HBs <10 mIU/mL. In 2010, 72.9% (416/571) of participants had anti-HBs ≥10 mIU/mL (67.3% in group A vs. 75.8% in group B; p 0.03). The geometric mean concentrations (GMCs) were similar in both groups. Between 2003 and 2010, anti-HBs concentrations in previously boosted individuals markedly declined with GMC dropping from 486 to 27.7 mIU/mL (p <0.001). Fifteen vaccinees showed a marked increase of antibody, possibly due to natural booster. In 2010, 96 individuals (37 of group A and 59 of group B) with anti-HBs <10 mIU/mL were boosted; all vaccinees of the former group and all but two of the latter had an anamnestic response. Post-booster GMC was higher in group B (895.6 vs. 492.2 mIU/mL; p 0.039). This finding shows that the immune memory for HBsAg persists beyond the time at which anti-HBs disappears, conferring long-term protection