A cis-regulatory element controls expression of histone deacetylase 9 to fine-tune inflammasome-dependent chronic inflammation in atherosclerosis.

Common genetic variants in a conserved cis-regulatory element (CRE) at histone deacetylase (HDAC)9 are a major risk factor for cardiovascular disease, including stroke and coronary artery disease. Given the consistency of this association and its proinflammatory properties, we examined the mechanisms whereby HDAC9 regulates vascular inflammation. HDAC9 bound and mediated deacetylation of NLRP3 in the NACHT and LRR domains leading to inflammasome activation and lytic cell death.

Polymersomes with splenic avidity target red pulp myeloid cells for cancer immunotherapy.

Regulating innate immunity is an emerging approach to improve cancer immunotherapy. Such regulation requires engaging myeloid cells by delivering immunomodulatory compounds to hematopoietic organs, including the spleen. Here we present a polymersome-based nanocarrier with splenic avidity and propensity for red pulp myeloid cell uptake.

Charting a course for global progress in PIDs by 2030 - proceedings from the IPOPI global multi-stakeholders' summit (September 2023).

The International Patient Organisation for Primary Immunodeficiencies (IPOPI) held its second Global Multi-Stakeholders' Summit, an annual stimulating and forward-thinking meeting uniting experts to anticipate pivotal upcoming challenges and opportunities in the field of primary immunodeficiency (PID). The 2023 summit focused on three key identified discussion points: (i) How can immunoglobulin (Ig) therapy meet future personalized patient needs? (ii) Pandemic preparedness: what's next for public health and potential challenges for the PID community? (iii) Diagnosing PIDs in 2030: what needs to happen to diagnose better and to diagnose more? Clinician-Scientists, patient representatives and other stakeholders explored avenues to improve Ig therapy through mechanistic insights and tailored Ig preparations/products according to patient-specific needs and local exposure to infectious agents, amongst others. Urgency for pandemic preparedness was discussed, as was the threat of shortage of antibiotics and increasing antimicrobial resistance, emphasizing the need for representation of PID patients and other vulnerable populations throughout crisis and care management.

Risk stratification refinements with inclusion of haemodynamic variables at follow-up in patients with pulmonary arterial hypertension.

Background: Haemodynamic variables are prognostic factors in pulmonary arterial hypertension (PAH). However, right heart catheterisation (RHC) is not systematically recommended to assess the risk status during follow-up. This study aimed to assess the added value of haemodynamic variables in prevalent patients to predict the risk of death or lung transplantation according to their risk status assessed by the non-invasive four-strata model as recommended by the European guidelines.

High risk of lung cancer in surfactant-related gene variant carriers.

Background: Several rare surfactant-related gene (SRG) variants associated with interstitial lung disease are suspected to be associated with lung cancer, but data are missing. We aimed to study the epidemiology and phenotype of lung cancer in an international cohort of SRG variant carriers.

Methods: We conducted a cross-sectional study of all adults with SRG variants in the OrphaLung network and compared lung cancer risk with telomere-related gene (TRG) variant carriers.

Overactivation of GnRH neurons is sufficient to trigger polycystic ovary syndrome-like traits in female mice.

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder leading to anovulatory infertility. Abnormalities in the central neuroendocrine system governed by gonadotropin-releasing hormone (GnRH) neurons might be related to ovarian dysfunction in PCOS, although the link in this disordered brain-to-ovary communication remains unclear. Here, we manipulated GnRH neurons using chemogenetics in adult female mice to unveil whether chronic overaction of these neurons would trigger PCOS-like hormonal and reproductive impairments.

Rituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD): a double-blind, randomised, placebo-controlled trial.

Background: Standard of care for interstitial lung disease (ILD) with a nonspecific interstitial pneumonia (NSIP) pattern proposes mycophenolate mofetil (MMF) as one of the first-step therapies while rituximab is used as rescue therapy.

Methods: In a randomised, double-blind, two-parallel group, placebo-controlled trial (NCT02990286), patients with connective tissue disease-associated ILD or idiopathic interstitial pneumonia (with or without autoimmune features) and a NSIP pattern (defined on NSIP pathological pattern or on integration of clinicobiological data and a NSIP-like high-resolution computed tomography pattern) were randomly assigned in a 1:1 ratio to receive rituximab (1000 mg) or placebo on day 1 and day 15 in addition to MMF (2 g daily) for 6 months. The primary end-point was the change in percent predicted forced vital capacity (FVC) from baseline to 6 months analysed by a linear mixed model for repeated measures analysis.

Dataset of night-time emissions of the Earth in the near UV range (290-430 nm), with 6.3 km resolution in the latitude range -51.6

The data presented in this article are related to the research paper entitled "" (Remote Sensing of Environment, Volume 284, January 2023, 113336, https://doi.org/10.1016/j.

Cell proliferation and glial cell marker expression in the wall of the third ventricle in the tuberal region of the male mouse hypothalamus during postnatal development.

The third ventricle (3 V) wall of the tuberal hypothalamus is composed of two types of cells; specialized ependymoglial cells called tanycytes located ventrally and ependymocytes dorsally, which control the exchanges between the cerebrospinal fluid and the hypothalamic parenchyma. By regulating the dialogue between the brain and the periphery, tanycytes are now recognized as central players in the control of major hypothalamic functions such as energy metabolism and reproduction. While our knowledge of the biology of adult tanycytes is progressing rapidly, our understanding of their development remains very incomplete.

Early pacemaker insertion after aortic valve replacement with an Edwards Intuity sutureless valve.

Background: Postoperative conduction disorders are serious adverse events in patients undergoing aortic valve replacement, and may prolong the duration of hospitalization and require pacemaker insertion.

Aim: Our aim was to evaluate the rate of pacemaker insertion after implantation of an Edwards Intuity sutureless aortic valve (Edwards Lifesciences, Irvine, CA, USA) compared with a standard surgical bioprosthesis.

Methods: This retrospective single-centre study included patients who underwent aortic valve replacement with an Intuity sutureless aortic valve or a standard bioprosthetic valve between 4 June 2014 and 27 June 2016.

GnRH replacement rescues cognition in Down syndrome.

At the present time, no viable treatment exists for cognitive and olfactory deficits in Down syndrome (DS). We show in a DS model (Ts65Dn mice) that these progressive nonreproductive neurological symptoms closely parallel a postpubertal decrease in hypothalamic as well as extrahypothalamic expression of a master molecule that controls reproduction-gonadotropin-releasing hormone (GnRH)-and appear related to an imbalance in a microRNA-gene network known to regulate GnRH neuron maturation together with altered hippocampal synaptic transmission. Epigenetic, cellular, chemogenetic, and pharmacological interventions that restore physiological GnRH levels abolish olfactory and cognitive defects in Ts65Dn mice, whereas pulsatile GnRH therapy improves cognition and brain connectivity in adult DS patients.

Female sexual behavior is disrupted in a preclinical mouse model of PCOS via an attenuated hypothalamic nitric oxide pathway.

Women with polycystic ovary syndrome (PCOS) frequently experience decreased sexual arousal, desire, and sexual satisfaction. While the hypothalamus is known to regulate sexual behavior, the specific neuronal pathways affected in patients with PCOS are not known. To dissect the underlying neural circuitry, we capitalized on a robust preclinical animal model that reliably recapitulates all cardinal PCOS features.

Micra AV leadless pacemaker implantation after transcatheter aortic valve implantation.

Background: Transvenous pacemaker (PM) implantation is a complication in patients undergoing transcatheter aortic valve implantation (TAVI). Recently, a second generation of leadless PMs able of atrioventricular (AV) synchronous pacing has been introduced and could be an alternative when ventricular pacing is required after TAVI. Real-world data on Micra AV after TAVI are still lacking.

External validation of a refined four-stratum risk assessment score from the French pulmonary hypertension registry.

Introduction: Contemporary risk assessment tools categorise patients with pulmonary arterial hypertension (PAH) as low, intermediate or high risk. A minority of patients achieve low risk status with most remaining intermediate risk. Our aim was to validate a four-stratum risk assessment approach categorising patients as low, intermediate-low, intermediate-high or high risk, as proposed by the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) investigators.

Ventilation/perfusion (V/Q) scanning in contemporary patients with pulmonary embolism: utilization rates and predictors of use in a multinational study.

Ventilation/perfusion (V/Q) imaging and computed tomography pulmonary angiography (CTPA) are common tools for acute pulmonary embolism (PE) diagnosis. Limited contemporary data exist about the utilization of each modality, including the predictors of using V/Q versus CTPA. We used the data from patients diagnosed with PE using V/Q or CTPA from 2007 to 2019 in Registro Informatizado Enfermedad ThromboEmbolica, an international prospective registry of patients with venous thromboembolism.

Gender Differences in Idiopathic Pulmonary Fibrosis: Are Men and Women Equal?

Idiopathic pulmonary fibrosis (IPF) is characterized by a male predominance. The aim of the study was to explore gender differences in a well-designed French multicentre prospective IPF cohort (COhorte FIbrose, COFI) with a 5-year follow-up. Between 2007 and 2010, 236 patients with incident IPF were included in COFI.

Targeting Trained Innate Immunity With Nanobiologics to Treat Cardiovascular Disease.

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Impact of pulmonary perfusion defects by scintigraphy on pulmonary vascular resistances, functional capacity and right ventricular systolic function in patients with chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a major cause of chronic pulmonary hypertension leading to right heart failure and death. Ventilation/perfusion single photon emission computed tomography (V/Q SPECT) is the screening test of choice showing mismatch in at least one segment or two sub-segments. Our aim was to investigate the relationship between the extent of pulmonary perfusion defects and hemodynamic, echocardiographic, biological and functional parameters.