HI intensity mapping with FAST

We discuss the detectability of large-scale HI intensity fluctuations using the FAST telescope. We present forecasts for the accuracy of measuring the Baryonic Acoustic Oscillations and constraining the properties of dark energy. The FAST $19$-beam L-band receivers ($1.05$--$1.45$ GHz) can provide constraints on the matter power spectrum and dark energy equation of state parameters ($w_{0},w_{a}$) that are comparable to the BINGO and CHIME experiments. For one year of integration time we find that the optimal survey area is $6000\,{\rm deg}^2$. However, observing with larger frequency coverage at higher redshift ($0.95$--$1.35$ GHz) improves the projected errorbars on the HI power spectrum by more than $2~\sigma$ confidence level. The combined constraints from FAST, CHIME, BINGO and Planck CMB observations can provide reliable, stringent constraints on the dark energy equation of state.Comment: 7 pages, 3 figures, submitted to "Frontiers in Radio Astronomy and FAST Early Sciences Symposium 2015" conference proceedin

Fifteen years trends of cardiogenic shock and mortality in patients with diabetes and acute coronary syndromes

PURPOSE: Our study was intended to examine time trends of management and mortality of acute coronary syndrome patients with associated diabetes mellitus. METHODS: We analyzed data from 5 nationwide registries established between 2001 and 2014, including consecutive acute coronary syndrome patients admitted to the Italian Intensive Cardiac Care Units. RESULTS: Of 28,225 participants, 8521 (30.2%) had diabetes: as compared with patients without diabetes, they were older and had significantly higher rates of prior myocardial infarction and comorbidities (all P < .0001). Prevalence of diabetes and comorbidities increased over time (P for trend < .0001). Cardiogenic shock rates were higher in patients with diabetes, as compared with those without diabetes (7.8% vs 2.8%, P < .0001), and decreased significantly over time only in patients without diabetes (P = .007). Revascularization rates increased over time in patients both with and without diabetes (both P for trend < .0001), although with persistingly lower rates in patients with diabetes. All-cause in-hospital mortality was higher in patients with diabetes (5.4 vs 2.5%, respectively, P < .0001) and decreased more consistently in patients without diabetes (P for trend = .007 and < .0001, respectively). At multivariable analysis, diabetes remains an independent predictor of both cardiogenic shock (odds ratio 2.03; 95% confidence interval, 1.77-2.32; P < .0001) and mortality (odds ratio 1.95; 95% confidence interval, 1.69-2.26; P < .0001). CONCLUSIONS: Despite significant mortality reductions observed over 15 years in acute coronary syndromes, patients with diabetes continue to show threefold higher rates of cardiogenic shock and lower revascularization rates as compared with patients without diabetes. These findings may explain the persistingly higher mortality of patients with diabetes and acute coronary syndromes

Induction of ER stress in response to oxygen-glucose deprivation of cortical cultures involves the activation of the PERK and IRE-1 pathways and of caspase-12

Disturbance of calcium homeostasis and accumulation of misfolded proteins in the endoplasmic reticulum (ER) are considered contributory components of cell death after ischemia. However, the signal-transducing events that are activated by ER stress after cerebral ischemia are incompletely understood. In this study, we show that caspase-12 and the PERK and IRE pathways are activated following oxygen-glucose deprivation (OGD) of mixed cortical cultures or neonatal hypoxia–ischemia (HI). Activation of PERK led to a transient phosphorylation of eIF2α, an increase in ATF4 levels and the induction of gadd34 (a subunit of an eIF2α-directed phosphatase). Interestingly, the upregulation of ATF4 did not lead to an increase in the levels of CHOP. Additionally, IRE1 activation was mediated by the increase in the processed form of xbp1, which would be responsible for the observed expression of edem2 and the increased levels of the chaperones GRP78 and GRP94. We were also able to detect caspase-12 proteolysis after HI or OGD. Processing of procaspase-12 was mediated by NMDA receptor and calpain activation. Moreover, our data suggest that caspase-12 activation is independent of the unfolded protein response activated by ER stress

Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model

<p>Abstract</p> <p>Background</p> <p>Acute quadriplegic myopathy (AQM) or critical illness myopathy (CIM) is frequently observed in intensive care unit (ICU) patients. To elucidate duration-dependent effects of the ICU intervention on molecular and functional networks that control the muscle wasting and weakness associated with AQM, a gene expression profile was analyzed at time points varying from 6 hours to 14 days in a unique experimental rat model mimicking ICU conditions, i.e., post-synaptically paralyzed, mechanically ventilated and extensively monitored animals.</p> <p>Results</p> <p>During the observation period, 1583 genes were significantly up- or down-regulated by factors of two or greater. A significant temporal gene expression pattern was constructed at short (6 h-4 days), intermediate (5-8 days) and long (9-14 days) durations. A striking early and maintained up-regulation (6 h-14d) of muscle atrogenes (muscle ring-finger 1/tripartite motif-containing 63 and F-box protein 32/atrogin-1) was observed, followed by an up-regulation of the proteolytic systems at intermediate and long durations (5-14d). Oxidative stress response genes and genes that take part in amino acid catabolism, cell cycle arrest, apoptosis, muscle development, and protein synthesis together with myogenic factors were significantly up-regulated from 5 to 14 days. At 9-14 d, genes involved in immune response and the caspase cascade were up-regulated. At 5-14d, genes related to contractile (myosin heavy chain and myosin binding protein C), regulatory (troponin, tropomyosin), developmental, caveolin-3, extracellular matrix, glycolysis/gluconeogenesis, cytoskeleton/sarcomere regulation and mitochondrial proteins were down-regulated. An activation of genes related to muscle growth and new muscle fiber formation (increase of myogenic factors and JunB and down-regulation of myostatin) and up-regulation of genes that code protein synthesis and translation factors were found from 5 to 14 days.</p> <p>Conclusions</p> <p>Novel temporal patterns of gene expression have been uncovered, suggesting a unique, coordinated and highly complex mechanism underlying the muscle wasting associated with AQM in ICU patients and providing new target genes and avenues for intervention studies.</p

Age and Diet Affect Gene Expression Profile in Canine Skeletal Muscle

We evaluated gene transcription in canine skeletal muscle (biceps femoris) using microarray analysis to identify effects of age and diet on gene expression. Twelve female beagles were used (six 1-year olds and six 12-year olds) and they were fed one of two experimental diets for 12 months. One diet contained primarily plant-based protein sources (PPB), whereas the second diet contained primarily animal-based protein sources (APB). Affymetrix GeneChip Canine Genome Arrays were used to hybridize extracted RNA. Age had the greatest effect on gene transcription (262 differentially expressed genes), whereas the effect of diet was relatively small (22 differentially expressed genes). Effects of age (regardless of diet) were most notable on genes related to metabolism, cell cycle and cell development, and transcription function. All these genes were predominantly down-regulated in geriatric dogs. Age-affected genes that were differentially expressed on only one of two diets were primarily noted in the PPB diet group (144/165 genes). Again, genes related to cell cycle (22/35) and metabolism (15/19) had predominantly decreased transcription in geriatric dogs, but 6/8 genes related to muscle development had increased expression. Effects of diet on muscle gene expression were mostly noted in geriatric dogs, but no consistent patterns in transcription were observed. The insight these data provide into gene expression profiles of canine skeletal muscle as affected by age, could serve as a foundation for future research pertaining to age-related muscle diseases

Protein quality control: the who’s who, the where’s and therapeutic escapes

In cells the quality of newly synthesized proteins is monitored in regard to proper folding and correct assembly in the early secretory pathway, the cytosol and the nucleoplasm. Proteins recognized as non-native in the ER will be removed and degraded by a process termed ERAD. ERAD of aberrant proteins is accompanied by various changes of cellular organelles and results in protein folding diseases. This review focuses on how the immunocytochemical labeling and electron microscopic analyses have helped to disclose the in situ subcellular distribution pattern of some of the key machinery proteins of the cellular protein quality control, the organelle changes due to the presence of misfolded proteins, and the efficiency of synthetic chaperones to rescue disease-causing trafficking defects of aberrant proteins

Are oral health conditions associated with schoolchildren's performance and school attendance in the Kingdom of Bahrain? A life-course perspective

Background The link between oral diseases and school performance and school attendance remains unclear among Middle Eastern children. Aim To investigate the relationship of oral conditions with schoolchildren’s school performance and attendance using the life course approach. Design A cross-sectional study was conducted with 466 schoolchildren aged 7-8 years from Kingdom of Bahrain (KoB) and their parents. Questionnaire data on children’s current and at birth environmental characteristics were completed by their parents. Children’s oral health measures, including ICDAS (International Caries Detection and Assessment System), PUFA (Pulp, Ulcer, Fistula, Abscess), and DDE (Developmental Defects of Enamel) indices, were the exposure variables. School performance and school attendance data obtained from the school register were the outcome variables. The data were analysed using multivariate ordinal logistic regression. Results The odds of Excellent school performance were significantly lower for children with untreated dentine caries (OR = 0.98 CI 95%: 0.96-0.99). Children with caries-treated teeth showed greater odds of Excellent school performance (OR=1.41 CI 95%: 1.15-1.74). A permissive parental style was associated with poor school attendance (OR= 2.63 CI 95%: 1.08-6.42). Conclusion Dental caries was associated with poor school performance but not with school attendance. Treated caries was associated with good school performance

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701