Role of Membrane Estrogen Receptor Alpha on the Positive Feedback of Estrogens on Kisspeptin and GnRH Neurons.

Estrogens act through nuclear and membrane-initiated signaling. Estrogen receptor alpha (ERα) is critical for reproduction, but the relative contribution of its nuclear and membrane signaling to the central regulation of reproduction is unclear. To address this question, two complementary approaches were used: estetrol (E) a natural estrogen acting as an agonist of nuclear ERs, but as an antagonist of their membrane fraction, and the C451A-ERα mouse lacking mERα.

Real-world evaluation of access-driven Canadian treatment sequences in progressive prostate cancer (REACTIVATE).

Introduction: The results of the phase 3 ALSYMPCA trial showed that Radium-223 (Ra-223) improves overall survival (OS) and delays onset of first symptomatic skeletal event vs. placebo in patients with metastatic castration-resistant prostate cancer (mCRPC). The purpose of the REACTIVATE study was to inform the optimal placement of Ra-233 in the treatment sequence by evaluating clinical outcomes and healthcare resource utilization using real-world data from multiple Canadian provinces.

Safety of immune checkpoint inhibitor rechallenge after severe immune-related adverse events: a retrospective analysis.

Immune checkpoint inhibitors (ICIs) present clinicians with the challenge of managing immune-related adverse events (irAEs), which can range from mild to severe due to immune system activation . While guidelines recommend discontinuing ICIs for grade 3 partial and all grade 4 irAEs, there is growing interest in rechallenging patients based on oncological outcomes, particularly for cardiovascular and neurological irAEs where data remains scarce . We retrospectively evaluated the safety of ICI rechallenge following grade 3-4 irAEs, specifically focusing on cardiovascular and neurological events, in patients discussed at our multidisciplinary immunotoxicity assessment board between 2019 and 2021.

Prospective cardiovascular events in patients with advanced thoracic cancer treated with immune checkpoint inhibitor.

Introduction: Myocarditis is the most lethal cardiovascular immune related adverse events with a low incidence, depending on the studies. We prospectively studied the potential interest of a systematic screening to early detect immune related myocarditis and confirm the incidence of immune-induced myocarditis in advanced lung cancer and the impact of troponin systematic screening in early detection of other major cardiovascular events (MACE).

Material And Methods: This prospective bicentric study includes adults who received at least one dose of immune checkpoint inhibitor (ICI) for advanced lung cancer.

The Equal Neutralizing Effectiveness of BNT162b2, ChAdOx1 nCoV-19, and Sputnik V Vaccines in the Palestinian Population.

Since the beginning of the COVID-19 pandemic, different viral vector-based and mRNA vaccines directed against the SARS-CoV-2 "S" spike glycoprotein have been developed and have shown a good profile in terms of safety and efficacy. Nevertheless, an unbiased comparison of vaccination efficiency, including post-vaccination neutralizing activity, between the different vaccines remains largely unavailable. This study aimed to compare the efficacy of one mRNA (BNT162b2) and two non-replicating adenoviral vector vaccines (ChAdOx1 nCoV-19 and Sputnik V) in a cohort of 1120 vaccinated Palestinian individuals who received vaccines on an availability basis and which displayed a unique diversity of genetic characteristics.

CALCOCO2/NDP52 associates with RAB9 to initiate an antiviral response to hepatitis B virus infection through a lysosomal degradation pathway.

CALCOCO2/NDP52 recognizes LGALS8 (galectin 8)-coated invading bacteria and initiates anti-bacterial autophagy by recruiting RB1CC1/FIP200 and TBKBP1/SINTBAD-AZI2/NAP1. Whether CALCOCO2 exerts similar functions against viral infection is unknown. In our recent study we show that CALCOCO2 targets envelope proteins of hepatitis B virus (HBV) to the lysosome for degradation, resulting in inhibition of viral replication.

Impaired reprogramming of the autophagy flux in maturing dendritic cells from crohn disease patients with core autophagy gene-related polymorphisms.

Crohn disease (CD) is an inflammatory bowel disease whose pathogenesis involves inappropriate immune responses toward gut microbiota on genetically predisposed backgrounds. Notably, CD is associated with single-nucleotide polymorphisms affecting several genes involved in macroautophagy/autophagy, the catabolic process that ensures the degradation and recycling of cytosolic components and microorganisms. In a clinical translation perspective, monitoring the autophagic activity of CD patients will require some knowledge on the intrinsic functional status of autophagy.

LC3B conjugation machinery promotes autophagy-independent HIV-1 entry in CD4 T lymphocytes.

HIV-1 entry into CD4 T lymphocytes relies on the viral and cellular membranes' fusion, leading to viral capsid delivery in the target cell cytoplasm. Atg8/LC3B conjugation to lipids, process named Atg8ylation mainly studied in the context of macroautophagy/autophagy, occurs transiently in the early stages of HIV-1 replication in CD4 T lymphocytes. Despite numerous studies investigating the HIV-1-autophagy interplays, the Atg8ylation impact in these early stages of infection remains unknown.

Real-world evaluation of access-driven Canadian treatment sequences in progressive prostate cancer (REACTIVATE).

Introduction: The results of the phase 3 ALSYMPCA trial showed that Radium-223 (Ra-223) improves overall survival (OS) and delays onset of first symptomatic skeletal event vs. placebo in patients with metastatic castration-resistant prostate cancer (mCRPC). The purpose of the REACTIVATE study was to inform the optimal placement of Ra-233 in the treatment sequence by evaluating clinical outcomes and healthcare resource utilization using real-world data from multiple Canadian provinces.

Sharing Digital Health Educational Resources in a One-Stop Shop Portal: Tutorial on the Catalog and Index of Digital Health Teaching Resources (CIDHR) Semantic Search Engine.

Background: Access to reliable and accurate digital health web-based resources is crucial. However, the lack of dedicated search engines for non-English languages, such as French, is a significant obstacle in this field. Thus, we developed and implemented a multilingual, multiterminology semantic search engine called Catalog and Index of Digital Health Teaching Resources (CIDHR).

Social isolation and aggression training lead to escalated aggression and hypothalamus-pituitary-gonad axis hyperfunction in mice.

Although the participation of sex hormones and sex hormone-responsive neurons in aggressive behavior has been extensively studied, the role of other systems within the hypothalamus-pituitary-gonadal (HPG) axis remains elusive. Here we assessed how the gonadotropin-releasing hormone (GnRH) and kisspeptin systems are impacted by escalated aggression in male mice. We used a combination of social isolation and aggression training (IST) to exacerbate mice's aggressive behavior.

Invisibility in global health: A case for disturbing bioethical frameworks.

In recent years, the global health community has increasingly reported the problem of 'invisibility': aspects of health and wellbeing, particularly amongst the world's most marginalized and impoverished people, that are systematically overlooked and ignored by people and institutions in relative positions of power. It is unclear how to realistically manage global health invisibility within bioethics and other social science disciplines and move forward. In this letter, we reflect on several case studies of invisibility experienced by people in Brazil, Malaysia, West Africa and other transnational contexts.

Long-term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humans.

Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH), an independent risk factor for non-alcoholic fatty liver disease (NAFLD). While the molecular links between IH and NAFLD progression are unclear, immune cell-driven inflammation plays a crucial role in NAFLD pathogenesis. Using lean mice exposed to long-term IH and a cohort of lean OSA patients (n = 71), we conducted comprehensive hepatic transcriptomics, lipidomics, and targeted serum proteomics.

Performance of Mucorales spp. qPCR in bronchoalveolar lavage fluid for the diagnosis of pulmonary mucormycosis.

To estimate the diagnostic performance of Mucorales polymerase chain reaction (PCR) in Bronchoalveolar lavage fluid (BALF) in routine practice. This was a single-center retrospective study including all consecutive patients >18 years who underwent Mucorales PCR assay in BALF between January 2021 and May 2022. Index testing was prospectively performed using the MycoGENIE Aspergillus spp.

NDP52 mediates an antiviral response to hepatitis B virus infection through Rab9-dependent lysosomal degradation pathway.

Autophagy receptor NDP52 triggers bacterial autophagy against infection. However, the ability of NDP52 to protect against viral infection has not been established. We show that NDP52 binds to envelope proteins of hepatitis B virus (HBV) and triggers a degradation process that promotes HBV clearance.

Origin of the central pit in hemimicelles of semifluorinated alkanes: How molecular dipoles and substrate deformation can determine supra-molecular morphology.

Hypothesis: Semifluorinated alkanes amphiphiles spontaneously form highly monodispersed hemimicelles at the surface of water. The origin of the formation and complex structure of these surprising supramolecular aggregates were only recently clarified using molecular dynamics simulations (MD). The existence of a pit at the center of these aggregates made up of almost 3000 molecules was indeed reproduced by the MD simulations, but not understood.

Multidisciplinary cardiogenic shock team approach improves the long-term outcomes of patients suffering from refractory cardiogenic shock treated with short-term mechanical circulatory support.

Aims: Short-term mechanical circulatory support (STMCS) may be used as an intentional escalation strategy to treat refractory cardiogenic shock (rCS). However, with growing technical possibilities, making the right choice at the right time can be challenging. We established a shock team in January 2013 comprising a cardiac anaesthetist-intensivist, an interventional cardiologist, and a cardiac surgeon.

Anti-SARS-CoV-2 (COVID-19) vaccination efficacy in patients with severe neuromuscular diseases.

Introduction: Patients with severe neuromuscular disease (sNMD) are considered at high risk of severe COVID-19. Muscle tissue is often replaced by fibroadipose tissue in these diseases whereas the new mRNA-based vaccines are injected intramuscularly. We aimed at evaluating the efficacy of two injections associated with a booster injection of mRNA vaccine in these patients.

Next generation antibacterial strategies for regenerative endodontic procedures: A scoping review.

Background: The clinical results following regenerative endodontic procedures (REPs) vary according to numerous parameters, including the presence of bacteria. This limitation reduces the indications for REPs and calls for the development of next generation antibacterial strategies (NGAS) providing alternatives to current antibacterial strategies (CAS) such as double or triple antibiotic paste (DAP/TAP) and (Ca(OH)2).

Objectives: The present scoping review aims to describe the current trends regarding the use of such strategies and highlight future perspectives.