Novel Orthosteric/Allosteric Ligands of Cannabinoid Receptors: An Unexpected Pharmacological Profile.

The design of dualsteric/bitopic receptor ligands as compounds capable of simultaneously interacting with both the orthosteric and an allosteric binding site has gained importance to achieve enhanced receptor specificity and minimize off-target effects. In this work, we reported the synthesis and biological evaluation of a new series of compounds, namely, the series, obtained by chemically combining the CB1R ago-positive allosteric modulators (PAM) with the cannabinoid receptors (CBRs) orthosteric agonist . Therefore, compounds were designed as dualsteric/bitopic ligands for CB1R with the aim of obtaining stronger CB1R agonists or ago-PAMs, with improved receptor subtype selectivity and reduction of central side effects.

Do SMS/e-mail reminders increase influenza vaccination of rheumatoid arthritis patients under anti-TNF: a nested randomized controlled trial in the ART e-cohort.

Objectives: To evaluate the effectiveness of short message service (SMS) and/or email reminders in improving influenza vaccination coverage rates among rheumatoid arthritis (RA) patients treated with anti-TNF therapies, and to identify factors associated with vaccination.

Methods: A nested randomized controlled trial in the ART e-cohort, an ongoing French nationwide multicentre prospective cohort of RA patients treated with anti-TNF therapy. Patients were 1:1 randomized, with stratification on age.

Pre-ADMET studies of 5-(3',4'-dihydroxyphenyl)-γ-valerolactone, the bioactive intestinal metabolite of proanthocyanidins.

5-(3',4'-Dihydroxyphenyl)-γ-valerolactone (VL) is a bioactive metabolite resulting from the gut microbial metabolism of proanthocyanidins and flavonoids, known for its health-promoting effects, including antidiabetic and anti-inflammatory activities. Although VL has been observed in different in vivo studies, its pre-absorption, distribution, metabolism, excretion, toxicity (ADMET) properties have rarely been investigated. This study aims to address this gap by evaluating the pre-ADMET properties of VL for the first time.

Bergamot (), a (Poly)Phenol-Rich Source for Improving Osteosarcopenic Obesity: A Systematic Review.

This systematic review investigates the potential of bergamot, a polyphenol-rich citrus fruit, in improving osteosarcopenic obesity, a condition characterized by the simultaneous presence of osteoporosis, obesity, and sarcopenia. Bergamot extracts have been suggested to possess several pharmacological properties, including anti-inflammatory and antioxidant effects, which could be useful in the management of age-related diseases and neuromuscular health. The review highlights the promising effects of bergamot extracts on skeletal muscle mass and function, particularly in the context of obesity, metabolic syndrome, osteosarcopenic obesity, and osteoporosis.

Revealing the Spatial Pattern of Brain Hemodynamic Sensitivity to Healthy Aging through Sparse Dynamic Causal Model.

Age-related changes in the BOLD response could reflect neurovascular coupling modifications rather than simply impairments in neural functioning. In this study, we propose the use of a sparse dynamic causal model (sDCM) to decouple neuronal and vascular factors in the BOLD signal, with the aim of characterizing the whole-brain spatial pattern of hemodynamic sensitivity to healthy aging, as well as to test the role of hemodynamic features as independent predictors in an age-classification model. sDCM was applied to the resting-state functional magnetic resonance imaging data of a cohort of 126 healthy individuals in a wide age range (31 females), providing reliable estimates of the hemodynamic response function (HRF) for each subject and each region of interest.

Perfect indications and how to avoid complications in lateral unicompartmental knee arthroplasty.

Lateral unicompartmental knee arthroplasty (LUKA) is a favorable alternative to distal femoral osteotomy and total knee arthroplasty in patients with isolated lateral compartment knee osteoarthritis; however, it only accounts for less than 1 ​% of the total number of knee replacements documented in national joint registries. The anatomy and biomechanics of the lateral knee compartment differ from the medial side, with a greater intrinsic laxity of the lateral collateral ligament complex compared with medial structures. Indications and surgical techniques must be tailored to each unicompartmental replacement to optimize outcomes and mitigate complications.

Analyzing asymmetry in brain hierarchies with a linear state-space model of resting-state fMRI data.

This study challenges the traditional focus on zero-lag statistics in resting-state functional magnetic resonance imaging (rsfMRI) research. Instead, it advocates for considering time-lag interactions to unveil the directionality and asymmetries of the brain hierarchy. Effective connectivity (EC), the state matrix in dynamical causal modeling (DCM), is a commonly used metric for studying dynamical properties and causal interactions within a linear state-space system description.

Mind the Gap: The Role of Mass Transfer in Shaped Nanoporous Adsorbents for Carbon Dioxide Capture.

Adsorptive separations by nanoporous materials are major industrial processes. The industrial importance of solid adsorbents is only expected to grow due to the increased focus on carbon dioxide capture technology and energy-efficient separations. To evaluate the performance of an adsorbent and design a separation process, the adsorption thermodynamics and kinetics must be known.

Screening of M Protease (SARS-CoV-2) Covalent Inhibitors from an Anthocyanin-Rich Blueberry Extract Using an HRMS-Based Analytical Platform.

Background: The viral main protease (M) of SARS-CoV-2 has been recently proposed as a key target to inhibit virus replication in the host. Therefore, molecules that can bind the catalytic site of M could be considered as potential drug candidates in the treatment of SARS-CoV-2 infections. Here we proposed the application of a state-of-the-art analytical platform which combines metabolomics and protein structure analysis to fish-out potential active compounds deriving from a natural matrix, i.

Importance of Characteristic Features and Their Form for Data Exploration.

The nature of the input features is one of the key factors indicating what kind of tools, methods, or approaches can be used in a knowledge discovery process. Depending on the characteristics of the available attributes, some techniques could lead to unsatisfactory performance or even may not proceed at all without additional preprocessing steps. The types of variables and their domains affect performance.

Extraction, purification and assessment of the antioxidant and anti-inflammatory activity of policosanols from non-psychoactive L.

Policosanols (PCs) are bioactive compounds extracted from different natural waxes. In this work, the purification, characterization and assessment of the antioxidant and anti-inflammatory activity was carried out on PCs from an innovative source, i.e.

Current and future burden from Lyme disease in Québec as a result of climate change.

Context: Environmental changes will foster the spread of ticks and increase the incidence of Lyme disease in Québec in the coming years. The objective of this study is to estimate the epidemiological and clinical burden and part of the current economic burden of Lyme disease in Québec and to estimate the number of cases expected by 2050.

Methods: Cases of Lyme disease reported in Québec from 2015 to 2019 were used to describe their demographic, geographical and clinical characteristics and the cost of their initial care.

Concise synthesis of deuterium-labelled proanthocyanidin metabolite 5-(3',4'-dihydroxyphenyl)-γ-valerolactone as an analytical tool.

Deuterated proanthocyanidin metabolite 5-(3',4'-dihydroxyphenyl)-γ-valerolactone has been successfully produced. This metabolite is responsible for several proanthocyanidin protective effects in the field of cancer chemoprevention, skin wrinkle-prevention, and antimicrobials. The synthetic approach applied employs a short reaction sequence and allows the incorporation of four deuterium atoms on non-exchangeable sites, making it an attractive strategy to produce a stable isotopically labeled internal standard for quantitative mass spectrometry isotope dilution-based methods, as demonstrated by developing an LC-MS/MS method to quantify DHPV in urine samples.

Macroscale coupling between structural and effective connectivity in the mouse brain.

Exploring how the emergent functional connectivity (FC) relates to the underlying anatomy (structural connectivity, SC) is one of the major goals of modern neuroscience. At the macroscale level, no one-to-one correspondence between structural and functional links seems to exist. And we posit that to better understand their coupling, two key aspects should be considered: the directionality of the structural connectome and limitations in explaining networks functions through an undirected measure such as FC.

Controlling target brain regions by optimal selection of input nodes.

The network control theory framework holds great potential to inform neurostimulation experiments aimed at inducing desired activity states in the brain. However, the current applicability of the framework is limited by inappropriate modeling of brain dynamics, and an overly ambitious focus on whole-brain activity control. In this work, we leverage recent progress in linear modeling of brain dynamics (effective connectivity) and we exploit the concept of target controllability to focus on the control of a single region or a small subnetwork of nodes.

Unraveling the parahormetic mechanism underlying the health-protecting effects of grapeseed procyanidins.

Proanthocyanidins (PACs), the predominant constituents within Grape Seed Extract (GSE), are intricate compounds composed of interconnected flavan-3-ol units. Renowned for their health-affirming properties, PACs offer a shield against a spectrum of inflammation associated diseases, such as diabetes, obesity, degenerations and possibly cancer. While monomeric and dimeric PACs undergo some absorption within the gastrointestinal tract, their larger oligomeric and polymeric counterparts are not bioavailable.

More rapid blood interferon α2 decline in fatal versus surviving COVID-19 patients.

Background: The clinical outcome of COVID-19 pneumonia is highly variable. Few biological predictive factors have been identified. Genetic and immunological studies suggest that type 1 interferons (IFN) are essential to control SARS-CoV-2 infection.

Biomedical doctoral students' research practices when facing dilemmas: two vignette-based randomized control trials.

Our aim was to describe the research practices of doctoral students facing a dilemma to research integrity and to assess the impact of inappropriate research environments, i.e. exposure to (a) a post-doctoral researcher who committed a Detrimental Research Practice (DRP) in a similar situation and (b) a supervisor who did not oppose the DRP.

Development of a 3D-Printable, Porous, and Chemically Active Material Filled with Silica Particles and its Application to the Fabrication of a Microextraction Device.

We report on the first successful attempt to produce a silica/polymer composite with retained C18 silica sorptive properties that can be reliably printed using three-dimensional (3D) FDM printing. A 3D printer provides an exceptional tool for producing complex objects in an easy and inexpensive manner and satisfying the current custom demand of research. Fused deposition modeling (FDM) is the most popular 3D-printing technique based on the extrusion of a thermoplastic material.

Enabling hydrate-based methane storage under mild operating conditions by periodic mesoporous organosilica nanotubes.

Biomethane is a renewable natural gas substitute produced from biogas. Storage of this sustainable energy vector in confined clathrate hydrates, encapsulated in the pores of a host material, is a highly promising avenue to improve storage capacity and energy efficiency. Herein, a new type of periodic mesoporous organosilica (PMO) nanotubes, referred to as hollow ring PMO (HR-PMO), capable of promoting methane clathrate hydrate formation under mild working conditions (273 K, 3.

Strategic Fast Induction Heating to Combat Hysteresis Barriers in a Flexible MOF for Rapid CO Desorption in Biogas Upgrading.

A major challenge in Cyclic Swing Separation using flexible adsorbents that have high equilibrium CO  adsorption capacity is their very low-pressure hysteresis that hinders efficient desorption. Mg-Gallate MOF is such a flexible adsorbent that only begins to release CO at its pore closing pressure at 0.08 bar and 30 °C, showing very slow and inefficient desorption in pressure or temperature swing.