[Adverse effects of licorice consumed as food: An update]. / Toxicités de l'exposition alimentaire à la réglisse : mise au point.

The word "licorice" refers to the plant, its root, and its aromatic extract. From a commercial point of view, Glycyrrhiza glabra is the most important species with a wide range of uses (herbal medicine, tobacco industry, cosmetics, food and pharmaceutical). Glycyrrhizin is one of the main constituents of licorice. Glycyrrhizin is hydrolyzed in the intestinal lumen by bacterial ß-glucuronidases to 3ß-monoglucuronyl-18ß-glycyrrhetinic acid (3MGA) and 18ß-glycyrrhetinic acid (GA), which are metabolized in the liver. Plasma clearance is slow due to enterohepatic cycling. 3MGA and GA can bind to mineralocorticoid receptors with very low affinity, and 3MGA induces apparent mineralocorticoid excess syndrome through dose-dependent inhibition of 11ß-hydroxysteroid dehydrogenase type 2 in renal tissue. The cases of apparent mineralocorticoid excess syndrome reported in the literature are numerous and sometimes severe, even fatal, most often in cases of chronic high dose consumption. Glycyrrhizin poisonings are characterized by hypertension, fluid retention, and hypokalemia with metabolic alkalosis and increased kaliuresis. Toxicity depends on the dose, the type of product consumed, the mode of consumption (acute or chronic) and a very large inter-individual variability. The diagnosis of glycyrrhizin-induced apparent mineralocorticoid excess syndrome is based on the history, clinical examination, and biochemical analysis. Management is primarily based on symptomatic care and stopping licorice consumption.

Issues and limitations of available biomarkers for fluoropyrimidine-based chemotherapy toxicity, a narrative review of the literature.

Fluoropyrimidine-based chemotherapies are widely used to treat gastrointestinal tract, head and neck, and breast carcinomas. Severe toxicities mostly impact rapidly dividing cell lines and can occur due to the partial or complete deficiency in dihydropyrimidine dehydrogenase (DPD) catabolism. Since April 2020, the European Medicines Agency (EMA) recommends DPD testing before any fluoropyrimidine-based treatment. Currently, different assays are used to predict DPD deficiency; the two main approaches consist of either phenotyping the enzyme activity (directly or indirectly) or genotyping the four main deficiency-related polymorphisms associated with 5-fluorouracil (5-FU) toxicity. In this review, we focused on the advantages and limitations of these diagnostic methods: direct phenotyping by evaluation of peripheral mononuclear cell DPD activity (PBMC-DPD activity), indirect phenotyping assessed by uracil levels or UH2/U ratio, and genotyping DPD of four variants directly associated with 5-FU toxicity. The risk of 5-FU toxicity increases with uracil concentration. Having a pyrimidine-related structure, 5-FU is catabolised by the same physiological pathway. By assessing uracil concentration in plasma, indirect phenotyping of DPD is then measured. With this approach, in France, a decreased 5-FU dose is systematically recommended at a uracil concentration of 16 ng/ml, which may lead to chemotherapy under-exposure as uracil concentration is a continuous variable and the association between uracil levels and DPD activity is not clear. We aim herein to describe the different available strategies developed to improve fluoropyrimidine-based chemotherapy safety, how they are implemented in routine clinical practice, and the possible relationship with inefficacy mechanisms.

Twice- or Once-Daily Dosing of Direct Oral Anticoagulants, a systematic review and meta-analysis.

AIM: The direct oral anticoagulants (DOAC) have similar half-lives, but the dosing regimen varies between once daily (QD) or twice daily (BID). For some prescribers, the QD regimen improves compliance. Others prefer BID regimens to promote better stability of plasma concentrations, particularly in the event of missed doses. Limited level of evidence provides guidance about the best treatment strategy. The purpose of this study was to compare the treatment effect of QD vs. BID administration of DOACs in major orthopedic surgery (MOS), non-valvular atrial fibrillation (NVAF), venous thromboembolism (VTE), and acute coronary syndrome (ACS). METHODS: We conducted a systematic review up to April 2020. We included phase II clinical trials comparing DOAC QD vs BID with same daily dose. We extracted data for the occurrence of major thrombosis (proximal deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke) and major hemorrhage (ISTH criteria and recommendations of the European Medicines Agency for surgical patients). Relative risks (RR) were combined using a fixed and random effects weighted meta-analysis. RESULTS: Twelve randomized, controlled, phase II trials were included (10,716 patients), representing 24 dosing regimen comparisons of apixaban, darexaban, edoxaban, rivaroxaban, letaxaban, and dabigatran. There was no difference for major thrombotic event (RRBID/QD = 1.06, 95%IC 0.86-1.30) nor for major bleeding (RRBID/QD = 1.02, 95%IC 0.84-1.23) between the BID vs QD regimens, without heterogeneity (I2 = 0%). CONCLUSION: Our study does not support a global difference in term of efficacy and safety of the BID and QD regimens of DOAC in MOS, NVAF, VTE and ACS.

Association between difference in blood pressure reduction and risk of cardiovascular events in a type 2 diabetes population: A meta-regression analysis.

AIM: Recent US recommendations indicate a target blood pressure (BP) of 130/80mmHg for patients with type 2 diabetes (T2D). Our aim was to characterize the association between risk of cardiovascular events and differences in BP decreases in randomized trials of a T2D population. METHODS: A systematic search was made for randomized clinical trials assessing the effects of antihypertensive treatments in T2D patients on mortality, and fatal and non-fatal cardiovascular events, using a meta-regression technique to explore the influence of BP decreases on treatment effects. RESULTS: A total of 88,503 patients from 44 randomized trials were included. There was no significant association between BP decreases and risk of all-cause or cardiovascular mortality, cardiovascular events or myocardial infarction. However, stroke risk was influenced by BP decreases: compared with no reduction, a 10-mmHg reduction in systolic BP was associated with a relative odds ratio (OR) decrease of 33% (OR: 0.67, 95% CI: 0.54-0.82), and a 5-mmHg diastolic BP reduction was associated with a relative OR decrease of 38% (OR: 0.62, 95% CI: 0.50-0.76). Restricting the analysis to double-blind studies did not change the results for diastolic BP. CONCLUSION: A reduction in BP lowers the risk of stroke, but does not appear to affect the risk of other cardiovascular events in a T2D population.

High expression of CPT1b in skeletal muscle in metabolically healthy older subjects.

AIM: Ageing is often associated with metabolic abnormalities such as insulin resistance, although some people remain metabolically healthy throughout their lives. The aim of this study was to gain more insight into metabolic health with increasing age. METHODS: Two groups of robust and of frail subjects, respectively, were identified based on a composite ageing indicator and recruited from the French SU.VI.MAX 2 cohort of older disease-free subjects. In all, 14 men and 12 women, aged 67±4 years, with similar anthropometric and metabolic characteristics at baseline (BMI: 24.5±2.9kg.m-2) were included in the Compaliclamp study. Skeletal muscle biopsy was performed to assess expression of a set of metabolic and sirtuin (SIRT) genes. Also, whole-body substrate oxidation and insulin sensitivity were determined using the euglycaemic-hyperinsulinaemic clamp and indirect calorimetry techniques. RESULTS: Robust subjects were more insulin-sensitive, oxidized more lipid in a fasting state and stored more glucose during the euglycaemic - hyperinsulinaemic clamp than did frail subjects. At the gene-expression level in skeletal muscle, carnitine palmitoyltransferase 1b (CPT1b) messenger RNA (mRNA) levels were around four times higher in the robust compared with frail counterparts. Moreover, both SIRT2 and SIRT6 expression was lower in robust subjects and correlated with CPT1b expression. CONCLUSION: CPT1b overexpression could be helping to maintain metabolic health with increasing age. Thus, it is suggested that targeting CPT1b expression might be an interesting strategy to counteract frailty at an early stage. In addition, future studies should examine the role of sirtuin in CPT1b expression regulation.

Growth optimization and characterization of regular arrays of GaAs/AlGaAs core/shell nanowires for tandem solar cells on silicon.

With a band gap value of 1.7 eV, Al0.2Ga0.8As is one of the ideal III-V alloys for the development of nanowire-based Tandem Solar Cells on silicon. Nevertheless, growing self-catalysed AlGaAs nanowires on silicon by solid-source molecular beam epitaxy is a very difficult task due to the oxidation of Al adatoms by the SiO2 layer present on the surface. Here we propose a nanowire structure including a p.i.n radial junction inside an Al0.2Ga0.8As shell grown on a p-GaAs core. The crystalline structure of such self-catalysed nanowires grown on an epi-ready Si(111) substrate (with a thin native SiO2 layer) was investigated by transmission electronic microscopy and photoluminescence. I(V) measurements performed on single nanowires have shown a diode-like behaviour corresponding to the radial p.i.n junction inside the Al0.2Ga0.8As shell. Moreover, a current generation under the electron beam was evidenced over the entire radial junction along the nanowires by means of electron beam induced current (EBIC) microscopy. The same structure was reproduced on patterned substrates with a SiO2 mask, producing an ordered hexagonal array. High and uniform yields from 83% to 87% of vertical nanowires were obtained on 0.9 × 0.9 cm2 patterned areas. EBIC mapping performed on these nanowires confirmed the good electrical properties of the radial junction within the nanowires.

GaAs nanowires with oxidation-proof arsenic capping for the growth of an epitaxial shell.

We propose an arsenic-capping/decapping method, allowing the growth of an epitaxial shell around the GaAs nanowire (NW) core which is exposed to an ambient atmosphere, and without the introduction of impurities. Self-catalyzed GaAs NW arrays were firstly grown on Si(111) substrates by solid-source molecular beam epitaxy. Aiming for protecting the active surface of the GaAs NW core, the arsenic-capping/decapping method has been applied. To validate the effect of this method, different core/shell NWs have been fabricated. Analyses highlight the benefit of the As capping-decapping method for further epitaxial shell growth: an epitaxial shell with a smooth surface is achieved in the case of As-capped-decapped GaAs NWs, comparable to the in situ grown GaAs/AlGaAs NWs. This As capping method opens a way for the epitaxial growth of heterogeneous material shells such as functional oxides using different reactors.

GaAs Core/SrTiO3 Shell Nanowires Grown by Molecular Beam Epitaxy.

We have studied the growth of a SrTiO3 shell on self-catalyzed GaAs nanowires grown by vapor-liquid-solid assisted molecular beam epitaxy on Si(111) substrates. To control the growth of the SrTiO3 shell, the GaAs nanowires were protected using an arsenic capping/decapping procedure in order to prevent uncontrolled oxidation and/or contamination of the nanowire facets. Reflection high energy electron diffraction, scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy were performed to determine the structural, chemical, and morphological properties of the heterostructured nanowires. Using adapted oxide growth conditions, it is shown that most of the perovskite structure SrTiO3 shell appears to be oriented with respect to the GaAs lattice. These results are promising for achieving one-dimensional epitaxial semiconductor core/functional oxide shell nanostructures.