Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase-deficient children receiving dapsone

Drug-induced acute hemolytic anemia led to the discovery of G6PD deficiency. However, most clinical data are from isolated case reports. In 2 clinical trials of antimalarial preparations containing dapsone (4,4′-diaminodiphenylsulfone; 2.5 mg/kg once daily for 3 days), 95 G6PD-deficient hemizygous boys, 24 G6PD-deficient homozygous girls, and 200 girls heterozygous for G6PD deficiency received this agent. In the first 2 groups, there was a maximum decrease in hemoglobin averaging -2.64 g/dL (range -6.70 to +0.30 g/dL), which was significantly greater than for the comparator group receiving artemether-lumefantrine (adjusted difference -1.46 g/dL; 95% confidence interval -1.76, -1.15). Hemoglobin concentrations were decreased by ≥ 40% versus pretreatment in 24/119 (20.2%) of the G6PD-deficient children; 13/119 (10.9%) required blood transfusion. In the heterozygous girls, the mean maximum decrease in hemoglobin was -1.83 g/dL (range +0.90 to -5.20 g/dL); 1 in 200 (0.5%) required blood transfusion. All children eventually recovered. All the G6PD-deficient children had the G6PD A- variant, ie, mutations V68MandN126D. Drug-induced acutehemolytic anemia in G6PD A- subjects can be life-threatening, depending on the nature and dosage of the drug trigger. Therefore, contrary to current perception, in clinical terms the A- type of G6PD deficiency cannot be regarded as mild. This study is registered at http://www.clinicaltrials.gov as NCT00344006 and NCT00371735. © 2012 by The American Society of Hematology

Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase-deficient children receiving dapsone

Drug-induced acute hemolytic anemia led to the discovery of G6PD deficiency. However, most clinical data are from isolated case reports. In 2 clinical trials of antimalarial preparations containing dapsone (4,4′-diaminodiphenylsulfone; 2.5 mg/kg once daily for 3 days), 95 G6PD-deficient hemizygous boys, 24 G6PD-deficient homozygous girls, and 200 girls heterozygous for G6PD deficiency received this agent. In the first 2 groups, there was a maximum decrease in hemoglobin averaging -2.64 g/dL (range -6.70 to +0.30 g/dL), which was significantly greater than for the comparator group receiving artemether-lumefantrine (adjusted difference -1.46 g/dL; 95% confidence interval -1.76, -1.15). Hemoglobin concentrations were decreased by ≥ 40% versus pretreatment in 24/119 (20.2%) of the G6PD-deficient children; 13/119 (10.9%) required blood transfusion. In the heterozygous girls, the mean maximum decrease in hemoglobin was -1.83 g/dL (range +0.90 to -5.20 g/dL); 1 in 200 (0.5%) required blood transfusion. All children eventually recovered. All the G6PD-deficient children had the G6PD A- variant, ie, mutations V68MandN126D. Drug-induced acutehemolytic anemia in G6PD A- subjects can be life-threatening, depending on the nature and dosage of the drug trigger. Therefore, contrary to current perception, in clinical terms the A- type of G6PD deficiency cannot be regarded as mild. This study is registered at http://www.clinicaltrials.gov as NCT00344006 and NCT00371735. © 2012 by The American Society of Hematology

Convective Vortices and Dust Devils Detected and Characterized by Mars 2020

We characterize vortex and dust devils (DDs) at Jezero from pressure and winds obtained with the Mars Environmental Dynamics Analyzer (MEDA) instrument on Mars 2020 over 415 Martian days (sols) (Ls = 6°–213°). Vortices are abundant (4.9 per sol with pressure drops >0.5 Pa correcting from gaps in coverage) and they peak at noon. At least one in every five vortices carries dust, and 75% of all vortices with Δp > 2.0 Pa are dusty. Seasonal variability was small but DDs were abundant during a dust storm (Ls = 152°–156°). Vortices are more frequent and intense over terrains with lower thermal inertia favoring high daytime surface-to-air temperature gradients. We fit measurements of winds and pressure during DD encounters to models of vortices. We obtain vortex diameters that range from 5 to 135 m with a mean of 20 m, and from the frequency of close encounters we estimate a DD activity of 2.0–3.0 DDs km−2 sol−1. A comparison of MEDA observations with a Large Eddy Simulation of Jezero at Ls = 45° produces a similar result. Three 100-m size DDs passed within 30 m of the rover from what we estimate that the activity of DDs with diameters >100 m is 0.1 DDs km−2sol−1, implying that dust lifting is dominated by the largest vortices in Jezero. At least one vortex had a central pressure drop of 9.0 Pa and internal winds of 25 ms−1. The MEDA wind sensors were partially damaged during two DD encounters whose characteristics we elaborate in detail.The authors are very grateful to the entire Mars 2020 science operations team. The authors would also like to thank Lori Fenton and an anonymous reviewer for many suggestions that greatly improved the manuscript. This work was supported by Grant PID2019-109467GB-I00 funded by MCIN/AEI/10.13039/501100011033/ and by Grupos Gobierno Vasco IT1742-22 and by the Spanish National Research, Development and Innovation Program, through the Grants RTI2018-099825-B-C31, ESP2016-80320-C2-1-R, and ESP2014-54256-C4-3-R. Baptiste Chide is supported by the Director's Postdoctoral Fellowship from the Los Alamos National Laboratory. M. Lemmon is supported by contract 15-712 from Arizona State University and 1607215 from Caltech-JPL. R. Lorenz was supported by JPL contract 1655893. Germán Martínez acknowledges JPL funding from USRA Contract Number 1638782. A. Munguira was supported by Grant PRE2020-092562 funded by MCIN/AEI and by “ESF Investing in your future.” A. Vicente-Retortillo is supported by the Spanish State Research Agency (AEI) Project No. MDM-2017-0737 Unidad de Excelencia “María de Maeztu”-Centro de Astrobiología (INTA-CSIC), and by the Comunidad de Madrid Project S2018/NMT-4291 (TEC2SPACE-CM). Part of the research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004). Finnish researchers acknowledge the Academy of Finland Grant 328 310529. Researchers based in France acknowledge support from the CNES for their work on Perseverance

The ESA Hera Mission : Detailed Characterization of the DART Impact Outcome and of the Binary Asteroid (65803) Didymos

Funding Information: To achieve these objectives, Milani is carrying two scientific payloads, the ASPECT visual and near-infrared (Vis-NIR) imaging spectrometer and the VISTA thermogravimeter aimed at collecting and characterizing volatiles and dust particles below 10 μm. Additionally, navigation payloads include a visible navigation camera and lidar. The Milani consortium is composed of entities and institutions from Italy, the Czech Republic, and Finland. The consortium Prime is Tyvak International, responsible for the whole program management and platform design, development, integration, testing, and final delivery to the customer. Politecnico di Torino is tasked with defining requirements and performing thermal, radiation, and debris analysis. Politecnico di Milano is responsible for mission analysis and GNC. Altec will support the Ground Segment architecture and interface definition. Centro Italiano per la Ricerca Aerospaziale (CIRA) is responsible for the execution of the vehicle environmental campaign. HULD contributes to developing the mission-specific software. VTT is the main payload (ASPECT hyperspectral imager) provider and is supported by the following entities dealing with ASPECT-related development: University of Helsinki (ASPECT calibration); Reaktor Space Lab (ASPECT Data Processing Unit development), Institute of Geology of the Czech Academy of Sciences (ASPECT scientific algorithms requirements and testing); and Brno University of Technology (ASPECT scientific algorithms development). INAF-IAPS is the secondary Payload (VISTA, dust detector) provider. Funding Information: The Mission PI is appointed by ESA and is the primary interface to ESA. The Hera SMB consists of the ESA Hera Project Scientist (ESA PS), the Mission PI, and the Hera Advisory Board, consisting of four mission advisors. The Mission PI chairs the HIT and is supported by the Hera Advisory Board. The tasks of the Hera SMB are 1. advising the Hera mission project team on all aspects related to the Hera mission objectives; 2. ensuring that the WGs’ activities cover the needs of the Hera mission; 3. providing recommendations to ESA concerning the membership in the HIT; and 4. implementing the Publication Policy. Funding Information: Hera is the ESA contribution to the AIDA collaboration. Hera, Juventas, Milani, and their instruments are developed under ESA contract supported by national agencies. This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 870377 (project NEO-MAPP), the CNRS through the MITI interdisciplinary programs, ASI, CNES, JAXA, the Academy of Finland project no. 335595, and was conducted with institutional support RVO 67985831 of the Institute of Geology of the Czech Academy of Sciences. M.L., E.P., P.T .and E.D. are grateful to the Italian Space Agency (ASI) for financial support through Agreement No. 2022-8-HH.0 in the context of ESA’s Hera mission. We are grateful to the whole Hera team, including Working Group core members and other contributors for their continuous efforts and support. Their names can be found on the following website: https:// www.heramission.space/team. Publisher Copyright: © 2022. The Author(s). Published by the American Astronomical Society.Hera is a planetary defense mission under development in the Space Safety and Security Program of the European Space Agency for launch in 2024 October. It will rendezvous in late 2026 December with the binary asteroid (65803) Didymos and in particular its moon, Dimorphos, which will be impacted by NASA’s DART spacecraft on 2022 September 26 as the first asteroid deflection test. The main goals of Hera are the detailed characterization of the physical properties of Didymos and Dimorphos and of the crater made by the DART mission, as well as measurement of the momentum transfer efficiency resulting from DART’s impact. The data from the Hera spacecraft and its two CubeSats will also provide significant insights into asteroid science and the evolutionary history of our solar system. Hera will perform the first rendezvous with a binary asteroid and provide new measurements, such as radar sounding of an asteroid interior, which will allow models in planetary science to be tested. Hera will thus provide a crucial element in the global effort to avert future asteroid impacts at the same time as providing world-leading science.Peer reviewe

Expression and Localization of Mitochondrial Ferritin mRNA in Alzheimer's Disease Cerebral Cortex

Mitochondrial ferritin (MtF) has been identified as a novel ferritin encoded by an intron-lacking gene with specific mitochondrial localization located on chromosome 5q23.1. MtF has been associated with neurodegenerative disorders such as Friedreich ataxia and restless leg syndrome. However, little information is available about MtF in Alzheimer's disease (AD). In this study, therefore, we investigated the expression and localization of MtF messenger RNA (mRNA) in the cerebral cortex of AD and control cases using real-time polymerase chain reaction (PCR) as well as in situ hybridization histochemistry. We also examined protein expression using western-blot assay. In addition, we used in vitro methods to further explore the effect of oxidative stress and β-amyloid peptide (Aβ) on MtF expression. To do this we examined MtF mRNA and protein expression changes in the human neuroblastoma cell line, IMR-32, after treatment with Aβ, H2O2, or both. The neuroprotective effect of MtF on oxidative stress induced by H2O2 was measured by MTT assay. The in situ hybridization studies revealed that MtF mRNA was detected mainly in neurons to a lesser degree in glial cells in the cerebral cortex. The staining intensity and the number of positive cells were increased in the cerebral cortex of AD patients. Real-time PCR and western-blot confirmed that MtF expression levels in the cerebral cortex were significantly higher in AD cases than that in control cases at both the mRNA and the protein level. Cell culture experiments demonstrated that the expression of both MtF mRNA and protein were increased by treatment with H2O2 or a combination of Aβ and H2O2, but not with Aβ alone. Finally, MtF expression showed a significant neuroprotective effect against H2O2-induced oxidative stress (p<0.05). The present study suggests that MtF is involved in the pathology of AD and may play a neuroprotective role against oxidative stress

Maternal Psychosocial Stress during Pregnancy and Placenta Weight: Evidence from a National Cohort Study

To study in a large-scale cohort with prospective data the associations between psychosocial stress during pregnancy and placenta weight at birth. Animal data suggest that the placenta is involved in stress-related fetal programming.; We defined a priori two types of psychosocial stress during pregnancy, life stress (perceived burdens in major areas of life) and emotional symptoms (e.g. anxiety). We estimated the associations of maternal stress during pregnancy with placenta weight at birth, controlled for length of gestation, by predicting gestational age- and sex-specific z-scores of placenta weight through multiple regression analysis, adjusted for potential confounders (N?=?78,017 singleton pregnancies). Life stress (per increase in stress score by 1, range: 0-18) during pregnancy was associated with increased placenta weight at birth (z-score, reported in 10(-3); B, 14.33; CI, 10.12-18.54). In contrast, emotional symptoms during pregnancy were not associated with placenta weight at birth.; Maternal life stress but not emotional symptoms during pregnancy was associated with increased placenta weight at birth; yet, the association-estimate was rather small. Our results may contribute to a better understanding of the role of the placenta in the regulation of intrauterine processes in response to maternal stress

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation