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Cette étude randomisée, multicentrique, menée en ouvert et cross-over, a évalué la préférence et la facilité d’utilisation du stylo injecteur somapacitan vs somatrogon.

Objective.The present work was framed to study the relationship between body mass index (BMI), blood pressure, and atherosclerosis risk factors on the basis of three lipid ratios in type 1 (T1D) and type 2 diabetic (T2D) patients.

De nombreuses techniques dites mini-invasives ont émergé ces dernières années dans le traitement chirurgical de l’obstruction due à l’hyperplasie bénigne de la prostate (HBP). L’objectif de cet article était de faire le point sur leurs évolutions et leurs résultats respectifs.

L’objectif du Comité des Troubles Mictionnels de l’Homme (CTMH) de l’Association Française d’Urologie (AFU) était de mettre à jour les recommandations françaises parues en 2012 et celles de l’EAU parues en 2019 concernant la prise en charge chirurgicale et interventionnelle de l’obstruction sous-vésicale (OSV) liée à une hyperplasie bénigne de prostate (HBP).

This study aims to investigate the potential of two local fibers, namely El Diss and El Retma, which are abundant in the mountains of North Africa (Sétif, Algeria), to provide cellulose nanocrystals (CNCs). Then, the isolated CNCs from El Diss were used as a reinforcement for a poly(vinyl alcohol-co-ethylene) matrix (EVOH) in the absence and in the presence of borax which was added to improve the interactions between the CNCs and the matrix. The extracted CNCs from both El Diss (CNCD) and El Retma (CNCR) were characterized by Zeta-sizer analysis using dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and scanning electronic microscopy. Also, untreated EVOH/CNCDnanocomposites and borax-treated EVOH/CNCD/BOR have been characterized using FTIR, differential scanning calorimetry (DSC) analyses, and by the study of their water absorption behavior. The DLS analysis provided the transversal length of the particles and showed that the surface of the obtained CNCs is negatively charged due to the presence of sulfated ions. Also, FTIR results confirmed the elimination of extra cellulosic substances, whereas TGA proved that the degradation of CNCs occurs at relatively lower temperatures compared with the neat fibers. The incorporation of borax to EVOH/CNCDnanocomposites showed its efficiency in improving the interactions at the interface between EVOH and the CNCD, which significantly affected the material’s thermal properties as concluded from DSC results and their water absorption behavior.

Plusieurs techniques de préservation des éjaculations ont été décrites pour la chirurgie de l’HBP.

Une enquête a été menée auprès des directeurs de programmes américains de formation postdoctorale en endocrinologie, entre le 19 janvier 2022 et le 28 mars 2022, afin de comprendre l’enseignement du déficit en hormone de croissance (GHD) après un traumatisme crânien (TBI) et d’en identifier les potentielles lacunes. Des courriers postaux et électroniques ont été utilisés pour recruter des répondants.

Confirmer la bioéquivalence des dosages de somapacitan 5mg/1,5ml et 10mg/1,5ml SC et étudier leurs propriétés PK/PD. (le somapacitan est une GH à longue durée d’action administrée hebdomadairement pour le traitement de l’AGHD)

Recombinant activated factor VII (rFVIIa; eptacog alfa activated, NovoSeven®, Novo Nordisk A/S) is a bypassing agent used in congenital hemophilia A patients with inhibitors. Emicizumab (Hemlibra®; F Hoffmann‐La Roche Ltd) is a recombinant, humanized, bispecific monoclonal antibody used for routine prophylaxis in patients with congenital hemophilia A with inhibitors. Concomitant use of the hemostatic agents rFVIIa and emicizumab carries a theoretical increased risk of thrombotic complications. Roche and Novo Nordisk collaboratively analyzed all available data on the use of rFVIIa in patients receiving emicizumab prophylaxis in the Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants With Inhibitors (HAVEN) clinical development program.

In the present study, the extraction conditions of phenolic compounds from the Ruta chalepensisL. (a medicinal plant) and the antioxidant activity of its extract were determined. The response surface methodology (RSM) flowing Box–Behnken design was used to study and optimise the effect of three factors [ethanol concentration (40–80%), sample to solvent ratio (0.05/10–0.5/10 g/mL) and extraction time (30–90 min)] on the total phenolic content (TPC) and the antioxidant activity (AA). The optimal extraction conditions predicted by the models were 50.33%, 0.28 g/10 mL, and 59.86 min for the ethanol concentration, the sample to solvent ratio and the extraction time, respectively. These factors gave the optimal predicted values of 521.10 mg GAE/g DW and of 60.48 mg AAE/g DW for the total phenolic content and the antioxidant activity, respectively. Total flavonoids (TFC), flavonols (TFlC), and ortho-diphenols (ODC) contents were further determined by evaluating the extract obtained by the validated optimal conditions of phenolic compounds. The obtained contents were 129.72 ± 1.09 mg QE/g DW, 24.98 ± 0.38 mg RE/g DW and 45.93 ± 0.37 mg CAE/g DW for TFC, TFlC, and ODC, respectively. The data of this report revealed that the extract of Ruta chalepensisL. is an excellent source of natural antioxidants that can be used or incorporated, as natural additives, into different food products in order to develop novel functional food products.

Improvements in aerodynamic turbomachinery design have gained attraction due to the increased demand for a more sustainable future. Several optimization approaches have been presented and employed in the realm of aerodynamic design. However, among all of them, the adjoint approach has emerged as a hot research topic for aerodynamic optimization in the field of turbomachinery. The ability of this method to efficiently compute the derivatives of objective functions for several design variables has made it a promising optimization tool. This study provides a comprehensive review of all significant studies undertaken since the turn of the 21st century when the adjoint method was employed for the aerodynamic optimization of turbomachinery applications. The application of the adjoint approach in that context is extensively discussed under various aspects, including shape optimization in both steady and unsteady flows, varied eddy viscosity, non-ideal compressible fluid-dynamics, multi-objective and multi-point optimizations, multidisciplinary optimization, coupling adjoint method with other approaches, parametrization methods, and uncertainty quantification. Finally, the review concludes by highlighting key points and outlooks on future developments.

To evaluate perioperative cost related to surgical treatments of benign prostatic obstruction (BPO): photoselective vaporization of the prostate (pvp), holmium/thullium laser enucleation (HoLEP/ThuLEP), transurethral resection of the prostate (TURP) and open prostatectomy (OP).

Supplemental Digital Content is available in the textHome therapy for uncomplicated mild/moderate bleeding can decrease healthcare burden, promote self-esteem, reduce complications, and provide near-normal quality of life. To evaluate recombinant activated factor VII (rFVIIa) as home therapy for joint bleeds in Algeria, Morocco, Oman, Saudi Arabia, and United Arab Emirates. Twenty-seven patients aged more than 2 years with congenital haemophilia and inhibitors were monitored for up to 8 months after a first haemarthrosis episode treated with rFVIIa. Assessments were made by patients/caregivers with a standardized diary. The main measures included home-managed bleeds, haemostasis, and pain relief within 9 h after first injection. Additional analyses included convenience, time to pain resolution, and doses given within 48 h. Of 132 bleeds, 84 (63.6%) were managed at home. Of these, successful haemostasis (partial or complete) was achieved at 9 h in 87.8%, with pain relief for 84.0%. For all treatment settings, successful haemostasis at 9 h was achieved for 86.3% of bleeds, with pain relief achieved for 74.8% of bleeds. Higher initial dosing was associated with fewer injections. Median time to complete haemostasis was 48 h (spontaneous bleeds) and 24 h (traumatic bleeds). Median time to complete pain relief was 24 h for both bleed types. Satisfaction with treatment was high. No safety concerns were reported. Results from this observational study agree with previous data on the safety and efficacy of home treatment with rFVIIa and will help to increase awareness and aggregate experience, fostering confidence in home management of haemophilia patients with inhibitors in developing countries.

The empirical pseudopotential method (EPM) within the virtual crystal approximation (VCA) is used to calculate the electronic and optical properties of ternary alloys ZnxCd1−xS, ZnxCd1−xSe, ZnSxSe1−xand MgxZn1−xSe. The alloy band structures and energy gaps are calculated using VCA which incorporates the compositional disorder as an effective potential. The calculated band structures for the ZnxCd1−xS, ZnxCd1−xSe and ZnSxSe1−xalloys show a direct band gap in the whole range of the concentration except for the MgxZn1−xSe alloy which presents a crossover from the direct gap to the indirect one.Also the dependence of the refractive index on the concentration is calculated for each ternary alloy. This parameter is found to depend nonlinearly on the alloy concentration. A detailed comparison of our results with experimental data and works of other authors has led to a good agreement.

This study investigates the estimation of the regression function using the kernel method in the presence of missing at random responses, assuming spatial dependence, and complete observation of the functional regressor. We construct the asymptotic properties of the established estimator and derive the probability convergence (with rates) as well as the asymptotic normality of the estimator under certain weak conditions. Simulation studies are then presented to examine and show the performance of our proposed estimator. This is followed by examining a real data set to illustrate the suggested estimator’s efficacy and demonstrate its superiority. The results show that the proposed estimator outperforms existing estimators as the number of missing at random data increases.

Les enjeux médicoéconomiques de la prise en charge médicamenteuse de l’hypertrophie bénigne de la prostate (HBP) prennent une importance croissante du fait du vieillissement de la population et de la multiplication des options thérapeutiques, d’où la nécessité d’évaluer le rapport coût–efficacité pour définir les stratégies les plus pertinentes économiquement. L’objectif était de réaliser une revue de la littérature des études médicoéconomiques sur la prise en charge médicamenteuse de l’HBP.

Les complications rares et sévères de la chirurgie de l’hyperplasie bénigne de la prostate (HBP) sont mal documentées dans la littérature. Notre objectif était de faire un état des lieux des complications graves et inattendues de l’HBP rencontrées par les urologues de l’Association française d’urologie (AFU).

Établir un guide de prise en charge à destinée des médecins généralistes pour la démarche diagnostique, le suivi et le traitement de symptômes du bas appareil urinaire (SBAU) liés à une hyperplasie bénigne de la prostate (HBP)

Les recommandations du Comité des troubles mictionnels de l’homme (CTMH) sur la prise en charge de l’hypertrophie bénigne de prostate (HBP) ont été diffusées en 2012. Aucune étude n’en a évalué l’impact. L’objectif de notre étude observationnelle était d’évaluer leur impact chez les urologues français.

Établir un état des lieux des connaissances sur la prise en charge de l’incontinence urinaire masculine non neurologique par traitement conservateurs et palliatifs non médicamenteux.

Établir une revue de la littérature sur la prise en charge de l’incontinence urinaire masculine non neurologique par hyperactivité vésicale (HV).

Abstract.Let LE2$L^2_E$be a Banach space of all ℙ-square integrable random variables defined on some probability space (Ω,풜,ℙ)$(\Omega ,\mathcal {A},\mathbb {P})$with values in the complex separable Banach space E. For an LE2$L_{E}^{2}$-valued stationary continuous random function 픛=(Xg)g∈G$\mathfrak {X}=(X_{g})_{g\in G}$on the locally compact abelian group G, we provide a condition of existence of a random measure Ztaking values in LE2$L^{2}_{E}$such that (Xg)g∈G$(X_{g})_{g\in G}$has a spectral representation as a Fourier transform of Z.

AbstractThe extraction of phenolic compounds from carob pulp was studied. The effects of solvent nature (acetone, ethanol, methanol and water), solvent concentration (40–100%), solid-to-solvent ratio (15/10 to 75/10 mg/ml), extraction time (60–120 min) and extraction temperature (25–90°C) were investigated. Total phenolic content and total flavonoid content were used for determination of phenolic compounds of carob pulp extract, whereas the antioxidant activity was assessed by measuring the free radical-scavenging activity and the ferric-reducing power. Experimental results showed that all examined parameters had statistically significant (p < 0.05) effects on phenolic compound extraction and antioxidant activities of extracts. The best extraction conditions were 70% acetone, 25 mg/10 ml, 90 min and 90°C with values of 3554 mgGAE/100 gDW, 1700 mgQE/100 gDW, 4032 mgAAE/100 gDW and 3929 mgAAE/100 gDW for the total phenolic content, the total flavonoid content, the free radical-scavenging activity and the ferric-reducing power, respectively. As a function of investigated extraction parameters, phenolic compound contents were positively correlated with antioxidant activities.

ABSTRACTCystic echinococcosis (CE) is a widespread and severe zoonotic disease caused by infection with the larval stage of the eucestode Echinococcus granulosussensu lato. The polymorphism exhibited by nuclear and mitochondrial markers conventionally used for the genotyping of different parasite species and strains does not reach the level necessary for the identification of genetic variants linked to restricted geographical areas. EmsB is a tandemly repeated multilocus microsatellite that proved its usefulness for the study of genetic polymorphisms within the species E. multilocularis, the causative agent of alveolar echinococcosis. In the present study, EmsB was used to characterize E. granulosussensu lato samples collected from different host species (sheep, cattle, dromedaries, dogs, and human patients) originating from six different countries (Algeria, Mauritania, Romania, Serbia, Brazil, and the People's Republic of China). The conventional mitochondrial cox1and nad1markers identified genotypes G1, G3, G5, G6, and G7, which are clustered into three groups corresponding to the species E. granulosussensu stricto, E. ortleppi, and E. canadensis. With the same samples, EmsB provided a higher degree of genetic discrimination and identified variations that correlated with the relatively small-scale geographic origins of the samples. In addition, one of the Brazilian single hydatid cysts presented a hybrid genotypic profile that suggested genetic exchanges between E. granulosussensu stricto and E. ortleppi. In summary, the EmsB microsatellite exhibits an interesting potential for the elaboration of a detailed map of the distribution of genetic variants and therefore for the determination and tracking of the source of CE.

PLEXUS-R (R for robotics) is an explicit computing program. Its variables are updated according to the time. This time (pseudo-continu) is updated in order to represent correctly the physical phenomenon. The calculation is done at every time step and the variable evolution is blocked between two successive time steps.

The photocycloaddition of vinyl acetate to enones bearing oxygenated functional groups on their p systems, such as the 1,3 dione enol ether 4a and the 1,3 dione 4b is expected to proceed with high regio and stereoselectivity. The bicyclo [5.2.1] dodecane derivative 3, an important structural element of simple model taxane diterpenes, was prepared in high yield by the photocycloaddition of enones 4a and 4b to vinyl acetate followed by opening of the thus formed cyclobutane ring, via the de Mayo reaction.

The use of an electronic regulator as control structure of an articulated mechanical system implies that converters are used on each side of the control. First, these converters insure the conversion of a physical value (mechanical state of the system) into an electrical value (measurement) in the case of a sensor placed above the control law and; second, the conversion of an electrical value (control) into a physical value (force or torque) in the case of the actuator placed below the control law (Foulard C and al, 1979).

The intermolecular [2+2] photocycloaddition of dimedone 6 and 1-acetoxy-2-methyl-5-dioxolan-1-hexene 7 followed by alkaline treatment, gave the 1,5,5,11-tetramethyl-7-dioxolan bicyclo [4,3,2]-4-decen-2,3-dione 12, and the 1,5,5-trimethyl-3-hydroxy-7-dioxolan bicyclo [5,4,1] dodecan-2,11-dione 13.

ABSTRACTA disseminated Fusarium oxysporuminfection with skin localization was diagnosed in a woman with a relapse of B-acute leukemia during induction chemotherapy. The infection was refractory to amphotericin B-lipid complex alone but responded successfully when voriconazole was added.

BackgroundThe nudix hydrolase 15 (NUDT15) polymorphism recently emerges as a biomarker of severe hematological toxicity during 6-mercaptopurine (6-MP) therapy of children with acute lymphoblastic leukemia (ALL). Initially described restricted to Asian population, recent publications highlighted its presence in patients with European ancestry. In November 2018, the Clinical Pharmacogenetics Implementation Consortium (CPIC) updated the guideline for thiopurines dosing based on Thiopurine S-methyl transferase (TPMT) and NUDT15genotypes. Here, we presented a feedback from a French monocentric experience in ALL patients.MethodsWe retrospectively genotyped 188 children for NUDT15c.94C>A treated for ALL at Trousseau hospital, Paris. Parents have given their consent for thiopurines’ therapeutic drug monitoring including performing TPMTgenotype (*2, *3B, *3C). We focused, for patients with a mutated NUDT15genotype, on treatment response in terms of morbi-mortality.ResultsThis NUDT15polymorphism was found for 6 patients (3.2%): one patient with a European ancestry and the others with an Asian ancestry. Five children had a NUDT15mutated heterozygous genotype without TPMTalterations and one patient with a mutated homozygous NUDT15genotype associated with TPMT*1/*3C. Hematological and/or infectious complications were reported for all patients with this variant with hospitalization in intensive care unit for the one with a mutated NUDT15genotype and TPMT*1/*3C. Reduced 6-MP dose (between 30% to 50% of the standard dose for heterozygous patients and 3% of the standard dose for mutated homozygous patient) was required for maintenance therapy. Two patients had a relapse.ConclusionThis report supports CPIC guidelines for screening NUDT15polymorphism before 6-MP treatment regardless patients‘ race. The impact of this polymorphism on relapse occurrence is worrying and prospective results with dose adjustments at 6-MP initiation will be crucial to understand if treatment interruptions and/or reduced dose were at risk of relapse.Disclosure(s)Nothing to disclose

Présenter les résultats obtenus avec un nouveau analyseur de biopuces permettant le dépistage simultané rapide de différents types de drogues (classiques, médicaments d’ordonnance et drogues synthétiques) à partir d’un échantillon de fluide oral.

BackgroundMercaptopurine (6-MP), a cornerstone of childhood acute lymphoblastic leukemia (ALL) therapy, is metabolized to active 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine nucleotides (6-MMPN) potentially hepatotoxic (threshold of 5000 pmol/8x108RBC). In few cases, the equilibrium between 6-TGN and 6-MMPN is unbalanced and in favor to 6-MMPN with high risk of inefficacy and toxicities. Here, we treated patients with allopurinol which inhibits Xanthine Oxidase and Thiopurine S-methyl Transferase (TPMT) implicated in methylation of thiopurines.MethodsTherapeutic drug monitoring of ALL patients was based on the determination of metabolites concentrations in red blood cells, measured by HPLC-UV after 3 weeks of stable 6-MP dose. After parental consent, individual genotypes are determined for TPMT(*2, *3B, *3C), ITPA(c.94C>A) and HLA*B5801(prior to allopurinol) by TaqMan allelic discrimination.ResultsIn 8 patients, 6-MMPN/6-TGN ratio was too high, superior to 50 (range: 58–248) with 6-TGN under therapeutic threshold (< 250 pmol/8x108RBC). All patients have a wild-type TPMTgenotype and for 3 patients, ITPApolymorphism could be involved to this disequilibrium. The co-administration of Allopurinol (50 mg n=5, 100 mg n=2), with a reduced 6-MP dose (around -50%) dose had a positive impact on metabolic ratio, inferior to 15 (range: < 1- 13) with metabolites levels inside therapeutic window and on resolving some toxicities (hypoglycemia (n=4), hepatotoxicity (n=3)). For one patient, 200 mg of Allopurinol was administered without reducing 6-MP dose, the metabolic ratio decreased from 115 to 63 but metabolites levels were both at supratherapeutic levels.ConclusionAllopurinol was effective in redirecting 6-MP metabolism to 6-TGN. A standardized protocol for this co-administration needs to be established and DNA-TGN incorporation dosage could be helpful for this recommendation. Long-term follow-up is required to evaluate impact on safety and efficacy of ALL maintenance therapy.Disclosure(s)Nothing to disclose

Cette étude met en évidence l’applicabilité d’une biopuce à la détection simultanée de buprénorphine, mitragynine, fentanyl et des composés et dérivés illicites du fentanyl à partir d’un seul échantillon d’urine.

Tramadol, a synthetic analogue of codeine, is used clinically as an analgesic for the treatment of moderate to moderately- severe pain. Tramadol expresses dual mechanism of action that includes weak agonistic effects at the μ-opioid receptors as well as inhibition of serotonin and norepinephrine uptake. Tramadol has two primary metabolites, N-desmethyl and O-desmethyl tramadol, the latter presenting greater affinity for μ-opioid receptors and twice the analgesic potency of the parent compound. Impairing side effects from the usage of tramadol include dizziness, confusion, light-headedness or fainting spells, drowsiness, seizures and respiratory depression. Much of the toxicity in tramadol overdose appears to be attributable to the monoamine uptake inhibition. This study reports the analytical evaluation of a newly developed enzyme-linked immunosorbent assay (ELISA) for the sensitive detection of tramadol and the active metabolite O-desmethyltramadol in urine and blood. This represents a useful analytical tool for applications in toxicology.

Introduction: SMART-7™ (NCT01220141) was a prospective, post-authorization, single-arm, multinational, multi-center, non-interventional study investigating the safety and effectiveness of room temperature stable rFVIIa (NovoSeven®) in patients with hemophilia A or B with inhibitors in a real-world setting. Here, we present a subgroup analysis of the hemostatic response of bleeding episodes to treatment with rFVIIa.

Benson: Novo Nordisk: Consultancy. Benchikh El Fegoun:Novo Nordisk: Employment. Cepo:Novo Nordisk: Employment. Sommer:Novo Nordisk: Employment. Kavakli:Novo Nordisk: Other: Steering committee meetings.

Synthétisés à l’origine dans un but thérapeutique, les cannabinoïdes de synthèse ont été détournés à de fins récréatives et abusives. Ce sont des composés chimiques structurellement différents du Δ9-tétrahydrocannabinol (THC), le principe actif du cannabis, mais ayant des effets pharmacologiques similaires. Additionnés à des mélanges d’herbes séchés et vendus sous le nom de « Spices », ils sont généralement fumés et vendus sur Internet et dans des magasins spécialisés. Le premier cannabinoïde de synthèse découvert était le JWH-018 (naphtalène-1-yl)(1-pentyl (1H-indole-3-yl)méthanone). En France, plusieurs cannabinoïdes de synthèse dont le JWH-018 ont été classés comme stupéfiants. L’AM-2201 (naphtalène-1-yl)([1-(5-fluoropentyl)-1H-indole-3-yl]méthanone) est le dérivé fluoré du JWH-018. Cette étude rapporte la performance analytique d’un nouveau kit pour le dépistage de JWH-018, AM-2201 et leurs métabolites dans l’urine (immunoanalyse en phase homogène). Ceci aide le processus d’analyse dans l’étape de criblage initiale.