Publications by authors named "J-H Lefebvre"
IL-1β Induces LDL Transcytosis by a Novel Pathway Involving LDLR and Rab27a.
Arterioscler Thromb Vasc Biol
September 2024
Background: In early atherosclerosis, circulating LDLs (low-density lipoproteins) traverse individual endothelial cells by an active process termed transcytosis. The CANTOS trial (Canakinumab Antiinflammatory Thrombosis Outcome Study) treated advanced atherosclerosis using a blocking antibody for IL-1β (interleukin-1β); this significantly reduced cardiovascular events. However, whether IL-1β regulates early disease, particularly LDL transcytosis, remains unknown.
View Article and Find Full Text PDFCommunity-Based Cluster-Randomized Trial to Reduce Opioid Overdose Deaths.
N Engl J Med
September 2024
Article Synopsis
- The study examines a community-based intervention aimed at reducing opioid-related overdose deaths by increasing the adoption of evidence-based practices including overdose education and naloxone distribution, medication treatment for opioid use disorder, and prescription safety.
- In a cluster-randomized trial, 67 communities across Kentucky, Massachusetts, New York, and Ohio were assigned to either receive the intervention or serve as a control group during a period marked by the COVID-19 pandemic and an increase in fentanyl overdoses.
- Results showed no significant difference in opioid-related overdose death rates between the intervention and control groups, with both averaging similar rates, indicating that the community-engaged strategies did not have a measurable impact during the study period.
Article Synopsis
- Background: The study examines brain MRI abnormalities in patients with severe COVID-19 (SARS-CoV-2) and identifies potential neurological issues related to the virus.
- Methods: Researchers analyzed data from 37 hospitalized patients who had neurological symptoms and abnormal brain MRIs between March and April 2020, excluding cases with ischemic strokes or unrelated chronic lesions.
- Results: The patient cohort, primarily older men, exhibited various neurological symptoms, with MRI findings showing significant abnormalities in brain regions including the medial temporal lobe and evidence of microhemorrhages, suggesting COVID-19's impact on brain structure.
Article Synopsis
- Research Focus and Methods
- : The study investigates the genetic factors influencing weight loss efficiency during dietary interventions in obese individuals by conducting a GWAS on two large cohorts undergoing low-caloric diets.
- Key Findings
- : Two significant genetic loci related to BMI were identified, specifically near NKX6.3/MIR486 and RBSG4, with findings replicated in an independent cohort.
- Biological Insights
- : Experimental manipulation of NKX6.3 in fruit flies showed a notable impact on triglyceride levels, highlighting its potential role in lipid metabolism and weight control in humans.
Article Synopsis
- The study aims to assess the safety and effectiveness of gene therapy as an alternative to long-term red-cell transfusions for patients with transfusion-dependent β-thalassemia, focusing on the use of a lentiviral vector to modify patients' cells.
- In two phase 1-2 trials involving 22 patients aged 12 to 35, researchers collected and modified the patients' own blood cells with a gene that encodes for adult hemoglobin, followed by reinfusing these cells after conditioning treatment.
- Results showed significant improvements: 12 out of 13 patients with a non-β/β genotype stopped needing transfusions, while those with the β/β genotype experienced a
Thousands of genetic variants have been associated with complex traits through genome-wide association studies. However, the functional variants or mechanistic consequences remain elusive. Intermediate traits such as gene expression or protein levels are good proxies of the metabolic state of an organism.
View Article and Find Full Text PDFContext: Somatostatin (SST) receptors (SSTRs) are expressed in a number of tissues, including the adrenal cortex, but their role in cortisol secretion has not been well characterized.
Objectives: The objective of the study was to investigate the expression of SSTRs in the adrenal cortex and cultured adrenocortical cells from primary pigmented nodular adrenocortical disease (PPNAD) tissues and to test the effect of a single injection of 100 μg of the SST analog octreotide on cortisol secretion in patients with PPNAD.
Setting And Design: The study was conducted at an academic research laboratory and clinical research center.