Antiplatelet therapy in atherothrombotic diseases : similarities and differences across guidelines

Antiplatelet therapy, mainly consisting of aspirin and P2Y12 receptor antagonists, is the cornerstone of the pharmacological treatment and prevention of atherothrombotic diseases. Its use, especially in secondary cardiovascular prevention, has significantly improved patient clinical outcomes in the last decades. Primary safety endpoint (i.e., bleeding complications) remain a major drawback of antiplatelet drugs. National and international societies have published and regularly updated guidelines for antiplatelet therapy aiming to provide clinicians with practical recommendations for a better handling of these drugs in various clinical settings. Many recommendations find common ground between international guidelines, but certain strategies vary across the countries, particularly with regard to the choice of molecules, dosage, and treatment duration. In this review, we detail and discuss the main antiplatelet therapy indications in the light of the different published guidelines and the significant number of recently published clinical trials and meta-analyses and highlight the areas that deserve further investigation in order to improve antiplatelet therapy in patients with atherothrombotic diseases

A subset of dendritic cells as a major and constitutive source of IL-22BP

Poster presentationInternational audienc

Reactive surveillance of suicides during the COVID-19 pandemic in France, 2020 to March 2022

Abstract Aims Mitigation actions during the COVID-19 pandemic may impact mental health and suicide in general populations. We aimed to analyse the evolution in suicide deaths from 2020 to March 2022 in France. Methods Using free-text medical causes in death certificates, we built an algorithm, which aimed to identify suicide deaths. We measured its retrospective performances by comparing suicide deaths identified using the algorithm with deaths which had either a Tenth revision of the International Classification of Diseases (ICD-10) code for ‘intentional self-harm’ or for ‘external cause of undetermined intent’ as the underlying cause. The number of suicide deaths from January 2020 to March 2022 was then compared with the expected number estimated using a generalized additive model. The difference and the ratio between the observed and expected number of suicide deaths were calculated on the three lockdown periods and for periods between lockdowns and after the third one. The analysis was stratified by age group and gender. Results The free-text algorithm demonstrated high performances. From January 2020 to mid-2021, suicide mortality declined during France’s three lockdowns, particularly in men. During the periods between and after the two first lockdowns, suicide mortality remained comparable to the expected values, except for men over 85 years old and in 65–84 year-old age group, where a small number of excess deaths was observed in the weeks following the end of first lockdown, and for men aged 45–64 years old, where the decline continued after the second lockdown ended. After the third lockdown until March 2022, an increase in suicide mortality was observed in 18–24 year-old age group for both genders and in men aged 65–84 years old, while a decrease was observed in the 25–44 year-old age group. Conclusions This study highlighted the absence of an increase in suicide mortality during France’s COVID-19 pandemic and a substantial decline during lockdown periods, something already observed in other countries. The increase in suicide mortality observed in 18–24 year-old age group and in men aged 65–84 years old from mid-2021 to March 2022 suggests a prolonged impact of COVID-19 on mental health, also described on self-harm hospitalizations and emergency department’s attendances in France. Further studies are required to explain the factors for this change. Reactive monitoring of suicide mortality needs to be continued since mental health consequences and the increase in suicide mortality may be continued in the future with the international context

Disruption of information processing in schizophrenia: The time perspective

AbstractWe review studies suggesting time disorders on both automatic and subjective levels in patients with schizophrenia. Patients have difficulty explicitly discriminating between simultaneous and asynchronous events, and ordering events in time. We discuss the relationship between these difficulties and impairments on a more elementary level. We showed that for undetectable stimulus onset asynchronies below 20ms, neither patients nor controls merge events in time, as previously believed. On the contrary, subjects implicitly distinguish between events even when evaluating them to be simultaneous. Furthermore, controls privilege the last stimulus, whereas patients seem to stay stuck on the first stimulus when asynchronies are sub-threshold. Combining previous results shows this to be true for patients even for asynchronies as short as 8ms. Moreover, this peculiarity predicts difficulties with detecting asynchronies longer than 50ms, suggesting an impact on the conscious ability to time events. Difficulties on the subjective level are also correlated with clinical disorganization. The results are interpreted within the framework of predictive coding which can account for an implicit ability to update events. These results complement a range of other results, by suggesting a difficulty with binding information in time as well as space, and by showing that information processing lacks continuity and stability in patients. The time perspective may help bridge the gap between cognitive impairments and clinical symptoms, by showing how the innermost structure of thought and experience is disrupted

ALMACAL IX: Multiband ALMA survey for dusty star-forming galaxies and the resolved fractions of the cosmic infrared background

Wide, deep, blind continuum surveys at submillimetre/millimetre (submm/mm) wavelengths are required to provide a full inventory of the dusty, distant Universe. However, conducting such surveys to the necessary depth, with sub-arcsec angular resolution, is prohibitively time-consuming, even for the most advanced submm/mm telescopes. Here, we report the most recent results from the ALMACAL project, which exploits the ‘free’ calibration data from the Atacama Large Millimetre/submillimetre Array (ALMA) to map the lines of sight towards and beyond the ALMA calibrators. ALMACAL has now covered 1001 calibrators, with a total sky coverage around 0.3 deg2, distributed across the sky accessible from the Atacama desert, and has accumulated more than 1000 h of integration. The depth reached by combining multiple visits to each field makes ALMACAL capable of searching for faint, dusty, star-forming galaxies (DSFGs), with detections at multiple frequencies to constrain the emission mechanism. Based on the most up-to-date ALMACAL data base, we report the detection of 186 DSFGs with flux densities down to S870 µm ∼ 0.2 mJy, comparable with existing ALMA large surveys but less susceptible to cosmic variance. We report the number counts at five wavelengths between 870 μm and 3 mm, in ALMA bands 3, 4, 5, 6, and 7, providing a benchmark for models of galaxy formation and evolution. By integrating the observed number counts and the best-fitting functions, we also present the resolved fraction of the cosmic infrared background (CIB) and the CIB spectral shape. Combining existing surveys, ALMA has currently resolved about half of the CIB in the submm/mm regime

Unconventional surface plasmon resonance signals reveal quantitative inhibition of transcriptional repressor EthR by synthetic ligands

International audienceEthR is a mycobacterial repressor that limits the bioactivation of ethionamide, a commonly used anti-tuberculosis second-line drug. Several efforts have been deployed to identify EthR inhibitors abolishing the DNA-binding activity of the repressor. This led to the demonstration that stimulating the bioactivation of ETH through EthR inhibition could be an alternative way to fight Mycobacterium tuberculosis. We propose a new SPR methodology to study the affinity between inhibitors and EthR. Interestingly, the binding between inhibitors and immobilized EthR produced a dose dependent negative SPR signal. We demonstrated that this signal reveals the affinity of the small molecules for the repressor. The affinity constants (KD) correlated with their capacity to inhibit the binding of EthR to DNA. We hypothesize that conformational changes of EthR during ligand interaction could be responsible for this SPR signal. Practically, this unconventional result open perspectives to the development of SPR assay that would at the same time tough on the structural changes of the target upon binding with an inhibitor and on the binding constant of this interaction

ALMACAL X: Constraints on molecular gas in the low-redshift circumgalactic medium

Despite its crucial role in galaxy evolution, the complex circumgalactic medium (CGM) remains underexplored. Although it is known to be multi-phase, the importance of the molecular gas phase to the total CGM mass budget is, to date, unconstrained. We present the first constraints on the molecular gas covering fraction in the CGM of low-redshift galaxies, using measurements of CO column densities along sightlines towards mm-bright background quasars with intervening galaxies. We do not detect molecular absorption against the background quasars. For the individual, low-redshift, ‘normal’ galaxy haloes probed here, we can therefore rule out the presence of an extremely molecular gas-rich CGM, as recently reported in high-redshift protoclusters and around luminous active galactic nuclei. We also set statistical limits on the volume filling factor of molecular material in the CGM as a whole, and as a function of radius. ISM-like molecular clouds of ∼30 pc in radius with column densities of N(CO) ≳ 1016 cm−2 have volume filling factors of less than 0.2 per cent. Large-scale smooth gas reservoirs are ruled out much more stringently. The development of this technique in the future will allow deeper constraining limits to be set on the importance (or unimportance) of molecular gas in the CGM

ALMACAL VI: Molecular gas mass density across cosmic time via a blind search for intervening molecular absorbers

We are just starting to understand the physical processes driving the dramatic change in cosmic star-formation rate between z ∼ 2 and the present day. A quantity directly linked to star formation is the molecular gas density, which should be measured through independent methods to explore variations due to cosmic variance and systematic uncertainties. We use intervening CO absorption lines in the spectra of mm-bright background sources to provide a census of the molecular gas mass density of the Universe. The data used in this work are taken from ALMACAL, a wide and deep survey utilizing the ALMA calibrator archive. While we report multiple Galactic absorption lines and one intrinsic absorber, no extragalactic intervening molecular absorbers are detected. However, thanks to the large redshift path surveyed (Δz = 182), we provide constraints on the molecular column density distribution function beyond z ∼ 0. In addition, we probe column densities of N(H2) > 1016 atoms cm−2, five orders of magnitude lower than in previous studies. We use the cosmological hydrodynamical simulation IllustrisTNG to show that our upper limits of ρ(H2) ≲ 108.3M⊙Mpc−3 at 0 < z ≤ 1.7 already provide new constraints on current theoretical predictions of the cold molecular phase of the gas. These results are in agreement with recent CO emission-line surveys and are complementary to those studies. The combined constraints indicate that the present decrease of the cosmic star-formation rate history is consistent with an increasing depletion of molecular gas in galaxies compared to z ∼ 2