Background: Patients with cancer are referred late to palliative care services (PCS).
Aim: To analyse the time of referral to PCSs and the characteristics of patients that are referred.
Methods: A retrospective cohort.
Cell motility is crucial for many biological processes including morphogenesis, wound healing, and cancer invasion. The WAVE regulatory complex (WRC) is a central Arp2/3 regulator driving cell motility downstream of activation by Rac GTPase. CYFIP-related Rac1 interactor (CYRI) proteins are thought to compete with WRC for interaction with Rac1 in a feedback loop regulating lamellipodia dynamics.
View Article and Find Full Text PDFBackground And Aims: Prophylactic implantable cardioverter-defibrillators (ICDs) are not recommended until left ventricular ejection fraction (LVEF) has been reassessed 40 to 90 days after an acute myocardial infarction. In the current therapeutic era, the prognosis of sustained ventricular arrhythmias (VAs) occurring during this early post-infarction phase (i.e.
View Article and Find Full Text PDFBackground And Aims: Cardiac Implantable Electronic Device (CIED) infections pose significant mortality and morbidity despite optimal treatment. This survey aimed to understand whether and how the risk of CIED infection is assessed and mitigated in clinical practice in Europe, and to detect gaps with respect to EHRA recommendations.
Methods: An Expert Group of 8 European cardiologists with specific expertise across CIED therapy designed and distributed electronically a survey to a number of European Cardiologists.
JACC Clin Electrophysiol
October 2024
Background: Electrical storm (ES) is a life-threatening condition, associated with substantial early and subacute mortality. Catheter ablation (CA) is a well-established therapy for ES. However, data regarding the impact of CA on the short-term and midterm survival of patients admitted for ES remain unclear.
View Article and Find Full Text PDFThe use of fluorescent proteins (FPs) in Plasmodium parasites has been key to understand the biology of this obligate intracellular protozoon. FPs like the green fluorescent protein (GFP) enabled to explore protein localization, promoter activity as well as dynamic processes like protein export and endocytosis. Furthermore, FP biosensors have provided detailed information on physiological parameters at the subcellular level, and fluorescent reporter lines greatly extended the malariology toolbox.
View Article and Find Full Text PDFSustainability in healthcare, particularly within the domain of cardiac electrophysiology, assumes paramount importance for the near future. The escalating environmental constraints encountered necessitate a proactive approach. This position paper aims to raise awareness among physicians, spark critical inquiry and identify potential solutions to enhance the sustainability of our practice.
View Article and Find Full Text PDFMalaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold.
View Article and Find Full Text PDFLipophorin is an essential, highly expressed lipid transport protein that is secreted and circulates in insect hemolymph. We hijacked the gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria parasite . The resulting transgenic mosquitoes show a markedly decreased ability to transmit expressing the circumsporozoite protein to mice.
View Article and Find Full Text PDFAntimicrobial resistance (AMR) is widely acknowledged as one of the most serious public health threats facing the world, yet the private sector finds it challenging to generate much-needed medicines. As an alternative discovery approach, a small array of diarylimidazoles was screened against the ESKAPE pathogens, and the results were made publicly available through the Open Source Antibiotics (OSA) consortium (https://github.com/opensourceantibiotics).
View Article and Find Full Text PDFBackground: The efficacy of beta-blocker treatment in type 3 long QT syndrome (LQT3) remains debated.
Objectives: The purpose of this study was to test the hypothesis that beta-blocker use is associated with cardiac events (CEs) in a French cohort of LQT3 patients.
Methods: All patients with a likely pathogenic/pathogenic variant in the SCN5A gene (linked to LQT3) were included and followed-up.
A class of DNA folds/structures known collectively as G-quadruplexes (G4) commonly forms in guanine-rich areas of genomes. G4-DNA is thought to have a functional role in the regulation of gene transcription and telomerase-mediated telomere maintenance and, therefore, is a target for drugs. The details of the molecular interactions that cause stacking of the guanine-tetrads are not well-understood, which limits a rational approach to the drugability of G4 sequences.
View Article and Find Full Text PDFMalaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold.
View Article and Find Full Text PDFLeishmaniasis is a collection of diseases caused by more than 20 parasite species that manifest as either visceral, cutaneous, or mucocutaneous leishmaniasis. Despite the significant mortality and morbidity associated with leishmaniasis, it remains a neglected tropical disease. Existing treatments have variable efficacy, significant toxicity, rising resistance, and limited oral bioavailability, which necessitates the development of novel and affordable therapeutics.
View Article and Find Full Text PDFEukaryotic cell adhesion and migration rely on surface adhesins connecting extracellular ligands to the intracellular actin cytoskeleton. Plasmodium sporozoites are transmitted by mosquitoes and rely on adhesion and gliding motility to colonize the salivary glands and to reach the liver after transmission. During gliding, the essential sporozoite adhesin TRAP engages actin filaments in the cytoplasm of the parasite, while binding ligands on the substrate through its inserted (I) domain.
View Article and Find Full Text PDFspecies, , and are opportunistic pathogens that cause a range of brain, skin, eye, and disseminated diseases in humans and animals. These pathogenic free-living amoebae (pFLA) are commonly misdiagnosed and have sub-optimal treatment regimens which contribute to the extremely high mortality rates (>90%) when they infect the central nervous system. To address the unmet medical need for effective therapeutics, we screened kinase inhibitor chemotypes against three pFLA using phenotypic drug assays involving CellTiter-Glo 2.
View Article and Find Full Text PDFExpression levels of microRNAs (miRNAs) in single cells are low and conventional miRNA detection methods require amplification that can be complex, time-consuming, costly and may bias results. Single cell microfluidic platforms have been developed; however, current approaches are unable to absolutely quantify single miRNA molecules expressed in single cells. Herein, we present an amplification-free sandwich hybridisation assay to detect single miRNA molecules in single cells using a microfluidic platform that optically traps and lyses individual cells.
View Article and Find Full Text PDFMalaria is caused by the unicellular parasite Plasmodium which is transmitted to humans through the bite of infected female Anopheles mosquitoes. To initiate sexual reproduction and to infect the midgut of the mosquito, Plasmodium gametocytes are able to recognize the intestinal environment after being ingested during blood feeding. A shift in temperature, pH change and the presence of the insect-specific compound xanthurenic acid have been shown to be important stimuli perceived by gametocytes to become activated and proceed to sexual reproduction.
View Article and Find Full Text PDFCurr Opin Microbiol
April 2023
During their development in mosquitoes, malaria parasites undergo massive losses that are in part due to a potent antiparasitic response mounted by the vector. The most efficient and best-characterized response relies on a complement-like system particularly effective against parasites as they cross the mosquito midgut epithelium. While our vision of the molecular and cellular events that lead to parasite elimination is still partial, our understanding of the steps triggering complement activation at the surface of invading parasites has considerably progressed, not only through the identification of novel contributing genes, but also with the recent in-depth characterization of the different mosquito blood cell types, and the ability to track them in live mosquitoes.
View Article and Find Full Text PDF