The COVID-19 pandemic has had a profound effect on general health care. We aimed to evaluate the effect of a nationwide lockdown in France on admissions to hospital for acute myocardial infarction, ...by patient characteristics and regional prevalence of the pandemic.
In this registry study, we collected data from 21 centres participating in the ongoing French Cohort of Myocardial Infarction Evaluation (FRENCHIE) registry, which collects data from all patients admitted for ST segment elevation myocardial infarction (STEMI) or non-ST segment elevation myocardial infarction (NSTEMI) within 48 h of symptom onset. We analysed weekly hospital admissions over 8 weeks: the 4 weeks preceding the institution of the lockdown and the 4 weeks following lockdown. The primary outcome was the change in the number of hospital admissions for all types of acute myocardial infarction, NSTEMI, and STEMI between the 4 weeks before lockdown and the 4 weeks after lockdown. Comparisons between categorical variables were made using χ2 tests or Fisher's exact tests. Comparisons of continuous variables were made using Student's t tests or Mann-Whitney tests. Poisson regression was used to determine the significance of change in hospital admissions over the two periods, after verifying the absence of overdispersion. Age category, region, and type of acute myocardial infarction (STEMI or NSTEMI) were used as covariables. The FRENCHIE cohort is registered with ClinicalTrials.gov, NCT04050956.
Between Feb 17 and April 12, 2020, 1167 patients were consecutively admitted within 48 h of acute myocardial infarction (583 with STEMI, 584 with NSTEMI) and were included in the study. Admissions for acute myocardial infarction decreased between the periods before and after lockdown was instituted, from 686 before to 481 after lockdown (30% decrease; incidence rate ratio 0·69 95% CI 0·51–0·70). Admissions for STEMI decreased from 331 to 252 (24%; 0·72 0·62–0·85), and admissions for NSTEMI decreased from 355 to 229 (35%; 0·64 0·55–0·76) following institution of the lockdown, with similar trends according to sex, risk factors, and regional prevalence of hospital admissions for COVID-19.
A marked decrease in hospital admissions was observed following the lockdown, irrespective of patient characteristics and regional prevalence of COVID-19. Health authorities should be aware of these findings, in order to adapt their message if the COVID-19 pandemic persists or recurs, or in case of future major epidemics.
Recherche Hospitalo-Universitaire en Santé iVasc.
The invention of next-generation sequencing (NGS) techniques marked the coming of a new era in the detection of the genetic diversity of intrahost viral populations. A good understanding of the ...genetic structure of these populations requires, first, the ability to identify the different isolates or variants and, second, the ability to accurately quantify them. However, the initial amplification step of NGS studies can impose potential quantitative biases, modifying the variant relative frequencies. In particular, the number of target molecules (NTM) used during the amplification step is vastly overlooked although of primary importance, as it sets the limit of the accuracy and sensitivity of the sequencing procedure. In the present article, we investigated quantitative biases in an NGS study of populations of a multipartite single-stranded DNA (ssDNA) virus at different steps of the procedure. We studied 20 independent populations of the ssDNA virus faba bean necrotic stunt virus (FBNSV) in two host plants,
and
FBNSV is a multipartite virus composed of eight genomic segments, whose specific and host-dependent relative frequencies are defined as the "genome formula." Our results show a significant distortion of the FBNSV genome formula after the amplification and sequencing steps. We also quantified the genetic bottleneck occurring at the amplification step by documenting the NTM of two genomic segments of FBNSV. We argue that the NTM must be documented and carefully considered when determining the sensitivity and accuracy of data from NGS studies.
The advent of next-generation sequencing (NGS) techniques now enables study of the genetic diversity of viral populations. A good understanding of the genetic structure of these populations first requires the ability to identify the different isolates or variants and second requires the ability to accurately quantify them. Prior to sequencing, viral genomes need to be amplified, a step that potentially imposes quantitative biases and modifies the viral population structure. In particular, the number of target molecules (NTM) used during the amplification step is of primary importance, as it sets the limit of the accuracy and sensitivity of the sequencing procedure. In this work, we used 20 replicated populations of the multipartite faba bean necrotic stunt virus (FBNSV) to estimate the various limitations of ultradeep-sequencing studies performed on intrahost viral populations. We report quantitative biases during rolling-circle amplification and the NTM of two genomic segments of FBNSV.
A founding paradigm in virology is that the spatial unit of the viral replication cycle is an individual cell. Multipartite viruses have a segmented genome where each segment is encapsidated ...separately. In this situation the viral genome is not recapitulated in a single virus particle but in the viral population. How multipartite viruses manage to efficiently infect individual cells with all segments, thus with the whole genome information, is a long-standing but perhaps deceptive mystery. By localizing and quantifying the genome segments of a nanovirus in host plant tissues we show that they rarely co-occur within individual cells. We further demonstrate that distinct segments accumulate independently in different cells and that the viral system is functional through complementation across cells. Our observation deviates from the classical conceptual framework in virology and opens an alternative possibility (at least for nanoviruses) where the infection can operate at a level above the individual cell level, defining a viral multicellular way of life.
Phenotypic plasticity in evolutionary rescue experiments Chevin, Luis-Miguel; Gallet, Romain; Gomulkiewicz, Richard ...
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
01/2013, Volume:
368, Issue:
1610
Journal Article
Peer reviewed
Open access
Population persistence in a new and stressful environment can be influenced by the plastic phenotypic responses of individuals to this environment, and by the genetic evolution of plasticity itself. ...This process has recently been investigated theoretically, but testing the quantitative predictions in the wild is challenging because (i) there are usually not enough population replicates to deal with the stochasticity of the evolutionary process, (ii) environmental conditions are not controlled, and (iii) measuring selection and the inheritance of traits affecting fitness is difficult in natural populations. As an alternative, predictions from theory can be tested in the laboratory with controlled experiments. To illustrate the feasibility of this approach, we briefly review the literature on the experimental evolution of plasticity, and on evolutionary rescue in the laboratory, paying particular attention to differences and similarities between microbes and multicellular eukaryotes. We then highlight a set of questions that could be addressed using this framework, which would enable testing the robustness of theoretical predictions, and provide new insights into areas that have received little theoretical attention to date.
Phosphorylation of sarcomeric proteins has been implicated in heart failure with preserved ejection fraction (HFpEF); such changes may contribute to diastolic dysfunction by altering contractility, ...cardiac stiffness, Ca
-sensitivity, and mechanosensing. Treatment with cardiosphere-derived cells (CDCs) restores normal diastolic function, attenuates fibrosis and inflammation, and improves survival in a rat HFpEF model.
Phosphorylation changes that underlie HFpEF and those reversed by CDC therapy, with a focus on the sarcomeric subproteome were analyzed.
Dahl salt-sensitive rats fed a high-salt diet, with echocardiographically verified diastolic dysfunction, were randomly assigned to either intracoronary CDCs or placebo. Dahl salt-sensitive rats receiving low salt diet served as controls. Protein and phosphorylated Ser, Thr, and Tyr residues from left ventricular tissue were quantified by mass spectrometry. HFpEF hearts exhibited extensive hyperphosphorylation with 98% of the 529 significantly changed phospho-sites increased compared with control. Of those, 39% were located within the sarcomeric subproteome, with a large group of proteins located or associated with the Z-disk. CDC treatment partially reverted the hyperphosphorylation, with 85% of the significantly altered 76 residues hypophosphorylated. Bioinformatic upstream analysis of the differentially phosphorylated protein residues revealed PKC as the dominant putative regulatory kinase. PKC isoform analysis indicated increases in PKC α, β, and δ concentration, whereas CDC treatment led to a reversion of PKCβ. Use of PKC isoform specific inhibition and overexpression of various PKC isoforms strongly suggests that PKCβ is the dominant kinase involved in hyperphosphorylation in HFpEF and is altered with CDC treatment.
Increased protein phosphorylation at the Z-disk is associated with diastolic dysfunction, with PKC isoforms driving most quantified phosphorylation changes. Because CDCs reverse the key abnormalities in HFpEF and selectively reverse PKCβ upregulation, PKCβ merits being classified as a potential therapeutic target in HFpEF, a disease notoriously refractory to medical intervention.
The appearance of plaques on a bacterial lawn is one of the enduring imageries in modern day biology. The seeming simplicity of a plaque has invited many hypotheses and models in trying to describe ...and explain the details of its formation. However, until now, there has been no systematic experimental exploration on how different bacteriophage (phage) traits may influence the formation of a plaque. In this study, we constructed a series of isogenic λ phages that differ in their adsorption rate, lysis timing, or morphology so that we can determine the effects if these changes on three plaque properties: size, progeny productivity, and phage concentration within plaques.
We found that the adsorption rate has a diminishing, but negative impact on all three plaque measurements. Interestingly, there exists a concave relationship between the lysis time and plaque size, resulting in an apparent optimal lysis time that maximizes the plaque size. Although suggestive in appearance, we did not detect a significant effect of lysis time on plaque productivity. Nonetheless, the combined effects of plaque size and productivity resulted in an apparent convex relationship between the lysis time and phage concentration within plaques. Lastly, we found that virion morphology also affected plaque size. We compared our results to the available models on plaque size and productivity. For the models in their current forms, a few of them can capture the qualitative aspects of our results, but not consistently in both plaque properties.
By using a collection of isogenic phage strains, we were able to investigate the effects of individual phage traits on plaque size, plaque productivity, and average phage concentration in a plaque while holding all other traits constant. The controlled nature of our study allowed us to test several model predictions on plaque size and plaque productivity. It seems that a more realistic theoretical approach to plaque formation is needed in order to capture the complex interaction between phage and its bacterium host in a spatially restricted environment.
Background: Paravalvular leak (PVL) is a recognized and challenging complication after surgical or transcatheter valve replacement. The transcatheter closure of PVL has become the first-line ...treatment in clinical practice when the procedure is not contraindicated. Transcatheter PVL closure rests on a complex procedure and complications still occur in approximately 9% of patients. Case Report: We describe the case of a delayed mechanical prosthetic leaflet impingement after transcatheter closure of a paravalvular leak associated with a Valsalva pseudoaneurysm that required an urgent surgery. Conclusion: Aorta–left ventricle communication could be a relative contraindication to be assessed on a case-by-case basis, but transcatheter closure does not preclude subsequent attempt for surgical repair and outcome.
Cauliflower mosaic virus (CaMV; family
) responds to the presence of aphid vectors on infected plants by forming specific transmission morphs. This phenomenon, coined transmission activation (TA), ...controls plant-to-plant propagation of CaMV. A fundamental question is whether other viruses rely on TA. Here, we demonstrate that transmission of the unrelated turnip mosaic virus (TuMV; family
) is activated by the reactive oxygen species H
O
and inhibited by the calcium channel blocker LaCl
H
O
-triggered TA manifested itself by the induction of intermolecular cysteine bonds between viral helper component protease (HC-Pro) molecules and by the formation of viral transmission complexes, composed of TuMV particles and HC-Pro that mediates vector binding. Consistently, LaCl
inhibited intermolecular HC-Pro cysteine bonds and HC-Pro interaction with viral particles. These results show that TuMV is a second virus using TA for transmission but using an entirely different mechanism than CaMV. We propose that TuMV TA requires reactive oxygen species (ROS) and calcium signaling and that it is operated by a redox switch.
Transmission activation, i.e., a viral response to the presence of vectors on infected hosts that regulates virus acquisition and thus transmission, is an only recently described phenomenon. It implies that viruses contribute actively to their transmission, something that has been shown before for many other pathogens but not for viruses. However, transmission activation has been described so far for only one virus, and it was unknown whether other viruses also rely on transmission activation. Here we present evidence that a second virus uses transmission activation, suggesting that it is a general transmission strategy.
The approach for veno-arterial extracorporeal membrane oxygenation implantation (VA-ECMO) in patients with cardiogenic shock can be either surgical or percutaneous. Complete angio-guided percutaneous ...implantation and explantation could decrease vascular complications. We sought to describe the initial results of complete percutaneous angio-guided ECMO implantation and explantation using preclosing.
All consecutive patients who underwent peripheral femoro-femoral VA-ECMO percutaneous implantation for refractory cardiogenic shock or cardiac arrest were enrolled in a prospective registry (03/2018-12/2020). Percutaneous preclosing using two closing devices (Perclose ProGlide, Abbott) inserted before cannulation was used in both femoral artery and vein. Explantation was performed using a crossover technique under angiographic guidance. The occurrence of vascular complication was recorded.
Among the 56 patients who underwent percutaneous VA-ECMO implantation for cardiogenic shock or refractory cardiac arrest, 41 underwent preclosing. Femoral vessel cannulation was successful in all patients and total cannulation time was 20 (10-40) min. Weaning from ECMO was possible in 22/41 patients (54%) and 12 (29%) patients were alive at day 30. Significant vascular complications occurred in 2/41 patients. Percutaneous decannulation was performed in 20 patients with 19/20 technical success rate. All femoral arteries and veins were properly closed using the pre-closing devices without bleeding on the angiographic control except for one patient in whom surgical closure of the artery was required. No patient required transfusion for access related significant bleeding and no other vascular complication occurred. Furthermore, no groin infection was observed after full percutaneous implantation and removal of ECMO.
Emergent complete percutaneous angio-guided VA-ECMO implantation and explantation using pre-closing technique can be an attractive strategy in patients referred for refractory cardiogenic shock.
Size is one of the most important biological traits influencing organismal ecology and evolution. However, we know little about the drivers of body size evolution in unicellulars. A long-term ...evolution experiment (Lenski's LTEE) in which Escherichia coli adapts to a simple glucose medium has shown that not only the growth rate and the fitness of the bacterium increase over time but also its cell size. This increase in size contradicts prominent 'external diffusion' theory (EDC) predicting that cell size should have evolved toward smaller cells. Among several scenarios, we propose and test an alternative 'internal diffusion-constraint' (IDC) hypothesis for cell size evolution. A change in cell volume affects metabolite concentrations in the cytoplasm. The IDC states that a higher metabolism can be achieved by a reduction in the molecular traffic time inside of the cell, by increasing its volume. To test this hypothesis, we studied a population from the LTEE. We show that bigger cells with greater growth and CO
production rates and lower mass-to-volume ratio were selected over time in the LTEE. These results are consistent with the IDC hypothesis. This novel hypothesis offers a promising approach for understanding the evolutionary constraints on cell size.
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