Association of perinatal sentinel events, placental pathology and cerebral MRI in neonates with hypoxic-ischemic encephalopathy receiving therapeutic hypothermia

OBJECTIVE: Placental pathology might provide information on the etiology of hypoxic-ischemic encephalopathy (HIE). To evaluate the association of perinatal sentinel events (PSE), placental pathology and cerebral MRI in cooled neonates with moderate/severe HIE. STUDY DESIGN: Retrospective analysis of 52 neonates with HIE registered in the Swiss National Asphyxia and Cooling Register 2011-2019. PSE and Non-PSE groups were tested for association with placental pathology. Placental pathology categories were correlated with MRI scores. RESULTS: In total, 14/52 neonates (27%) had a PSE, 38 neonates (73%) did not have a PSE. There was no evidence for an association of occurrence of PSE and placental pathologies (p = 0.364). Neonates with high MRI scores tended to have more often chronic pathologies in their placentas than acute pathologies or normal placentas (p = 0.067). CONCLUSION: Independent of the occurrence of PSE, chronic placental pathologies might be associated with more severe brain injury and needs further study

Placental findings are not associated with neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy - an 11-year single-center experience

OBJECTIVES: Although neonates with moderate to severe hypoxic ischemic encephalopathy (HIE) receive therapeutic hypothermia (TH), 40-50% die or have significant neurological disability. The aim of this study is to analyse the association of placental pathology and neurodevelopmental outcome in cooled neonates with HIE at 18-24 months of age. METHODS: Retrospective analysis of prospectively collected data on 120 neonates registered in the Swiss National Asphyxia and Cooling Register born between 2007 and 2017. This descriptive study examines the frequency and range of pathologic findings in placentas of neonates with HIE. Placenta pathology was available of 69/120 neonates, whose results are summarized as placental findings. As neonates with HIE staged Sarnat score 1 (21/69) did not routinely undergo follow-up assessments and of six neonates staged Sarnat Score 2/3 no follow-up assessments were available, 42/48 (88%) neonates remain to assess the association between placental findings and outcome. RESULTS: Of the 42/48 (88%) neonates with available follow up 29% (12/42) neonates died. Major placenta abnormalities occurred in 48% (20/42). Major placenta abnormality was neither associated with outcome at 18-24 months of age (OR 1.75 [95% CI 0.50-6.36, p=0.381]), nor with death by 2 years of age (OR 1.96 [95% CI 0.53-7.78, p=0.320]). CONCLUSIONS: In this study cohort there could not be shown an association between the placenta findings and the neurodevelopmental outcome at 18-24 months of age

Discovery of the 2010 Eruption and the Pre-Eruption Light Curve for Recurrent Nova U Scorpii

We report the discovery by B. G. Harris and S. Dvorak on JD 2455224.9385 (2010 Jan 28.4385 UT) of the predicted eruption of the recurrent nova U Scorpii (U Sco). We also report on 815 magnitudes (and 16 useful limits) on the pre-eruption light curve in the UBVRI and Sloan r' and i' bands from 2000.4 up to 9 hours before the peak of the January 2010 eruption. We found no significant long-term variations, though we did find frequent fast variations (flickering) with amplitudes up to 0.4 mag. We show that U Sco did not have any rises or dips with amplitude greater than 0.2 mag on timescales from one day to one year before the eruption. We find that the peak of this eruption occurred at JD 2455224.69+-0.07 and the start of the rise was at JD 2455224.32+-0.12. From our analysis of the average B-band flux between eruptions, we find that the total mass accreted between eruptions is consistent with being a constant, in agreement with a strong prediction of nova trigger theory. The date of the next eruption can be anticipated with an accuracy of +-5 months by following the average B-band magnitudes for the next ~10 years, although at this time we can only predict that the next eruption will be in the year 2020+-2.Comment: Astronomical Journal submitted, 36 pages, 3 figures, full table

The MUSIC of Galaxy Clusters I: Baryon properties and Scaling Relations of the thermal Sunyaev-Zel'dovich Effect

We introduce the Marenostrum-MultiDark SImulations of galaxy Clusters (MUSIC) Dataset, one of the largest sample of hydrodynamically simulated galaxy clusters with more than 500 clusters and 2000 groups. The objects have been selected from two large N-body simulations and have been resimulated at high resolution using SPH together with relevant physical processes (cooling, UV photoionization, star formation and different feedback processes). We focus on the analysis of the baryon content (gas and star) of clusters in the MUSIC dataset both as a function of aperture radius and redshift. The results from our simulations are compared with the most recent observational estimates of the gas fraction in galaxy clusters at different overdensity radii. When the effects of cooling and stellar feedbacks are included, the MUSIC clusters show a good agreement with the most recent observed gas fractions quoted in the literature. A clear dependence of the gas fractions with the total cluster mass is also evident. The impact of the aperture radius choice, when comparing integrated quantities at different redshifts, is tested: the standard definition of radius at a fixed overdensity with respect to critical density is compared with a definition based on the redshift dependent overdensity with respect to background density. We also present a detailed analysis of the scaling relations of the thermal SZ (Sunyaev Zel'dovich) Effect derived from MUSIC clusters. The integrated SZ brightness, Y, is related to the cluster total mass, M, as well as, the M-Y counterpart, more suitable for observational applications. Both laws are consistent with predictions from the self-similar model, showing a very low scatter. The effects of the gas fraction on the Y-M scaling and the presence of a possible redshift dependence on the Y-M scaling relation are also explored.Comment: 22 pages, 25 figures, accepted for pubblication by MNRA

CERT\u3csub\u3eL\u3c/sub\u3e Reduces C16 Ceramide, Amyloid-β Levels, and Inflammation in a Model of Alzheimer’s Disease

BACKGROUND: Dysregulation of ceramide and sphingomyelin levels have been suggested to contribute to the pathogenesis of Alzheimer\u27s disease (AD). Ceramide transfer proteins (CERTs) are ceramide carriers which are crucial for ceramide and sphingomyelin balance in cells. Extracellular forms of CERTs co-localize with amyloid-β (Aβ) plaques in AD brains. To date, the significance of these observations for the pathophysiology of AD remains uncertain. METHODS: A plasmid expressing CERTL, the long isoform of CERTs, was used to study the interaction of CERTL with amyloid precursor protein (APP) by co-immunoprecipitation and immunofluorescence in HEK cells. The recombinant CERTL protein was employed to study interaction of CERTL with amyloid-β (Aβ), Aβ aggregation process in presence of CERTL, and the resulting changes in Aβ toxicity in neuroblastoma cells. CERTL was overexpressed in neurons by adeno-associated virus (AAV) in a mouse model of familial AD (5xFAD). Ten weeks after transduction, animals were challenged with behavior tests for memory, anxiety, and locomotion. At week 12, brains were investigated for sphingolipid levels by mass spectrometry, plaques, and neuroinflammation by immunohistochemistry, gene expression, and/or immunoassay. RESULTS: Here, we report that CERTL binds to APP, modifies Aβ aggregation, and reduces Aβ neurotoxicity in vitro. Furthermore, we show that intracortical injection of AAV, mediating the expression of CERTL, decreases levels of ceramide d18:1/16:0 and increases sphingomyelin levels in the brain of male 5xFAD mice. CERTL in vivo over-expression has a mild effect on animal locomotion, decreases Aβ formation, and modulates microglia by decreasing their pro-inflammatory phenotype. CONCLUSION: Our results demonstrate a crucial role of CERTL in regulating ceramide levels in the brain, in amyloid plaque formation and neuroinflammation, thereby opening research avenues for therapeutic targets of AD and other neurodegenerative diseases

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Eclipses During the 2010 Eruption of the Recurrent Nova U Scorpii

The eruption of the recurrent nova U Scorpii on 28 January 2010 is now the all-time best observed nova event. We report 36,776 magnitudes throughout its 67 day eruption, for an average of one measure every 2.6 minutes. This unique and unprecedented coverage is the first time that a nova has any substantial amount of fast photometry. With this, two new phenomena have been discovered: the fast flares in the early light curve seen from days 9-15 (which have no proposed explanation) and the optical dips seen out of eclipse from days 41-61 (likely caused by raised rims of the accretion disk occulting the bright inner regions of the disk as seen over specific orbital phases). The expanding shell and wind cleared enough from days 12-15 so that the inner binary system became visible, resulting in the sudden onset of eclipses and the turn-on of the supersoft X-ray source. On day 15, a strong asymmetry in the out-of-eclipse light points to the existence of the accretion stream. The normal optical flickering restarts on day 24.5. For days 15-26, eclipse mapping shows that the optical source is spherically symmetric with a radius of 4.1 R_sun. For days 26-41, the optical light is coming from a rim-bright disk of radius 3.4 R_sun. For days 41-67, the optical source is a center-bright disk of radius 2.2 R_sun. Throughout the eruption, the colors remain essentially constant. We present 12 eclipse times during eruption plus five just after the eruption.Comment: ApJ in press. 60 pages, 17 figure

The Entomopathogenic Bacterial Endosymbionts Xenorhabdus and Photorhabdus: Convergent Lifestyles from Divergent Genomes

Members of the genus Xenorhabdus are entomopathogenic bacteria that associate with nematodes. The nematode-bacteria pair infects and kills insects, with both partners contributing to insect pathogenesis and the bacteria providing nutrition to the nematode from available insect-derived nutrients. The nematode provides the bacteria with protection from predators, access to nutrients, and a mechanism of dispersal. Members of the bacterial genus Photorhabdus also associate with nematodes to kill insects, and both genera of bacteria provide similar services to their different nematode hosts through unique physiological and metabolic mechanisms. We posited that these differences would be reflected in their respective genomes. To test this, we sequenced to completion the genomes of Xenorhabdus nematophila ATCC 19061 and Xenorhabdus bovienii SS-2004. As expected, both Xenorhabdus genomes encode many anti-insecticidal compounds, commensurate with their entomopathogenic lifestyle. Despite the similarities in lifestyle between Xenorhabdus and Photorhabdus bacteria, a comparative analysis of the Xenorhabdus, Photorhabdus luminescens, and P. asymbiotica genomes suggests genomic divergence. These findings indicate that evolutionary changes shaped by symbiotic interactions can follow different routes to achieve similar end points