Obstructive sleep apnoea syndrome promotes reversal albuminuria during sleep

Sleep apnoea syndrome (OSAS) may induce albuminuria during sleep which could reflect one of the possible pathogenetic mechanisms regarding cardiovascular risk. We studied 224 patients with newly diagnosed OSAS, free of any chronic disease, and any regular drug therapy. The levels of urine albumin/creatinine ratio (ACR) before (ACR-bsleep) and immediately after (ACR-asleep) a sleep study were determined. The same procedure was repeated during the first night on CPAP treatment (n = 121) and in 46 reevaluated patients, after 3 months, on CPAP therapy. Ambulatory blood pressure was monitored in 133 of the patients. ACR-asleep was significantly higher in patients (17.82 +/- 31.10 mg/g) compared with controls (6.54 +/- 6.53 mg/g, p < 0.001). The mean percent change in ACR levels between after and before sleep (%dACR) was increased by 8.82% +/- 61.06 in OSAS patients and reduced by 26.87% +/- 18.95 in controls (p < 0.001). During the first sleep study on CPAP, the %dACR was reduced by 21.40% +/- 24.59, in contrast to the increase observed during the initial study (10.73% +/- 69.93, p < 0.001). This beneficial effect of CPAP treatment was preserved in the reevaluated patients. The %dACR was +29.33% +/- 57.67 in nondippers (44% of the patients) and -5.57% +/- 40.81 in dippers (p < 0.001). It was negatively correlated to the percent change of systolic (rho = -0.284, p = 0.003) and diastolic (rho = -0.341, p < 0.001) blood pressure between wakefulness and sleep. Contrary to normal people, ACR is increased in OSAS patients during sleep, at least partially, related to the nondipping phenomenon observed in these patients. Following CPAP treatment, urinary albumin excretion is reduced

Genomic analyses inform on migration events during the peopling of Eurasia

High-coverage whole-genome sequence studies have so far focused on a limited number1 of geographically restricted populations2,3,4,5, or been targeted at specific diseases, such as cancer6. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history7,8,9 and refuelled the debate on the mutation rate in humans10. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record11, and admixture between AMHs and Neanderthals predating the main Eurasian expansion12, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago

Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial.

BACKGROUND: Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1-2%. The CRASH trial--a multicentre international collaboration--aimed to confirm or refute such an effect by recruiting 20000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment. METHODS: 10008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN74459797. FINDINGS: Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21.1%] vs 893 [17.9%] deaths; relative risk 1.18 [95% CI 1.09-1.27]; p=0.0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0.22) or time since injury (p=0.05). INTERPRETATION: Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear