The DExD/H box ATPase Dhh1 functions in translational repression, mRNA decay, and processing body dynamics

Dhh1 is a critical determinant in whether mRNAs are translated, stored, or decayed

Distinct Type of Transmission Barrier Revealed by Study of Multiple Prion Determinants of Rnq1

Prions are self-propagating protein conformations. Transmission of the prion state between non-identical proteins, e.g. between homologous proteins from different species, is frequently inefficient. Transmission barriers are attributed to sequence differences in prion proteins, but their underlying mechanisms are not clear. Here we use a yeast Rnq1/[PIN+]-based experimental system to explore the nature of transmission barriers. [PIN+], the prion form of Rnq1, is common in wild and laboratory yeast strains, where it facilitates the appearance of other prions. Rnq1's prion domain carries four discrete QN-rich regions. We start by showing that Rnq1 encompasses multiple prion determinants that can independently drive amyloid formation in vitro and transmit the [PIN+] prion state in vivo. Subsequent analysis of [PIN+] transmission between Rnq1 fragments with different sets of prion determinants established that (i) one common QN-rich region is required and usually sufficient for the transmission; (ii) despite identical sequences of the common QNs, such transmissions are impeded by barriers of different strength. Existence of transmission barriers in the absence of amino acid mismatches in transmitting regions indicates that in complex prion domains multiple prion determinants act cooperatively to attain the final prion conformation, and reveals transmission barriers determined by this cooperative fold

Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected]. BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS o

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

AB0269 UTILITY OF DAS28-γGT IN THE ASSESSMENT OF DISEASE ACTIVITY AND CARDIOVASCULAR RISK IN RHEUMATOID ARTHRITIS

BackgroundɣGT has been identified as a maker of systemic inflammation and cardiovascular (CV) risk. The composite index DAS28-ɣGT has been developed to allow an evaluation of both joint disease activity and CV risk.ObjectivesTo assess the value of the DAS28-ɣGT in a population of patients with rheumatoid arthritis (RA) requesting cardiologic assessment.MethodsRetrospective analysis of RA patients referred to cardio-metabolic day hospitalization in the Rheumatology department of Cochin hospital between February 2021 and January 2022. Criteria for referral were age &gt; 50 years and presence of at least one CV risk factor. DAS28-GGT index was calculated as follows: 0,56 * √TJ-28 + 0,28 * √SJ-28 + 2 * ln (γGT) + 0,14 * GH. This index was analysed according to disease activity measured with the DAS28-CRP, CV risk assessed by the Framingham score and the decision taken by the cardiologist (requirement of complementary explorations and/or therapeutic intervention).ResultsWe included 22 RA patients (17 women), with a mean age of 66±10 years, a disease duration of 21±12 years. Rheumatoid factor was positive in 15 patients, anti-CCP antibodies in 17, and bone erosions in 16. 15 patients received methotrexate, 13 corticosteroids (dose &lt; 10 mg per day), 15 targeted biologic therapies and 3 JAK inhibitors. The mean DAS28-CRP was 2.5±0.9 and the mean DAS28-ɣGT was 7.90±1.90.2 patients had a DAS28-ɣGT &lt; 5.5, defined in our previous study as high probability of RA remission and low probability of CV risk. These two patients were in remission and their Framingham score was &lt; 10% (low CV risk). No complementary exploration was requested by the cardiologist.8 patients (6 women, 2 men) had a DAS28-ɣGT index between 5,5 and 7,5, defined in our previous study as high probability of RA remission or low disease activity (LDA) and increased probability of CV risk. As expected, all patients were in remission or in LDA. This population were at higher CV risk: 2 patients had a Framingham score &gt; 20% (high risk), 3 patients a score ranging from 10 to 20% (intermediate risk), and 3 patients a score &lt; 10%. One patient presented carotid atheroma. 4 patients required additional CV explorations and 3 patients necessitated escalation of blood hypertension therapy.Twelve patients (9 women, 3 men) had a DAS28-ɣGT index &gt; 7,5, defined in our previous study as high probability of active RA and/or increased probability of CV risk. 4 patients were in remission, 3 were in LDA and 5 presented moderate disease activity. One patient had a Framingham score &gt; 20%, 4 had a score ranging between 10 and 20% and 6 had a score &lt; 10%. The score was not applicable in an 80-year-old patient. Three other patients had coronary artery disease, including a patient who presented both coronary artery disease and carotid atheroma. 5 patients requested additional CV explorations and 4 required CV therapy escalation (introduction of statin and aspirin in 2 patients and increased blood hypertension therapy in 2 patients). Among these 12 patients, 3 with the highest DAS28-ɣGT values presented CV complications: a 64-year-old woman with a DAS28-ɣGT of 12.8 (DAS28-CRP: 2.89) had carotid atheroma and intermediate lesion of the right artery on coroscanner justifying a coronarography; a 81-year-old woman with a DAS28-ɣGT of 10.67 (DAS29-CRP: 4.62) had atrial fibrillation and aortic stenosis requiring Transcatheter Aortic Valve Implantation; and a 77-year-old woman with a DAS28-ɣGT of 10.35 (DAS28-CRP: 3.89) had ischemic chest pain necessitating rapid explorations in cardiology.ConclusionThe DAS28-ɣGT allowed a reliable classification of patients according to the RA activity disease and CV risk. This index may be relevant for CV risk stratification decision making to refer RA patients to a cardiologist. Its validation is in progress in a prospective cohort.References[1]Vergneault H, vandebeuque E, Codullo V, et al, J rheumatol 2020;47(12):1738-1745Disclosure of InterestsNone declared</jats:sec