Sustainable Primary Cell Banking for Topical Compound Cytotoxicity Assays: Protocol Validation on Novel Biocides and Antifungals for Optimized Burn Wound Care.

Thorough biological safety testing of topical therapeutic compounds and antimicrobials is a critical prerequisite for appropriate cutaneous wound care. Increasing pathogen resistance rates to traditional antibiotics and antifungals are driving the development and registration of novel chemical entities. Although they are notably useful for animal testing reduction, the gold standard in vitro cytotoxicity assays in continuous cell lines (HaCaT keratinocytes, 3T3 fibroblasts) may be discussed from a translational relevance standpoint.

Three-Dimensional Measurement of the Uterus on Magnetic Resonance Images: Development and Performance Analysis of an Automated Deep-Learning Tool.

Uterus measurements are useful for assessing both the treatment and follow-ups of gynaecological patients. The aim of our study was to develop a deep learning (DL) tool for fully automated measurement of the three-dimensional size of the uterus on magnetic resonance imaging (MRI). In this single-centre retrospective study, 900 cases were included to train, validate, and test a VGG-16/VGG-11 convolutional neural network (CNN).

Impact of artificial intelligence in breast cancer screening with mammography.

Objectives: To demonstrate that radiologists, with the help of artificial intelligence (AI), are able to better classify screening mammograms into the correct breast imaging reporting and data system (BI-RADS) category, and as a secondary objective, to explore the impact of AI on cancer detection and mammogram interpretation time.

Methods: A multi-reader, multi-case study with cross-over design, was performed, including 314 mammograms. Twelve radiologists interpreted the examinations in two sessions delayed by a 4 weeks wash-out period with and without AI support.

Local Tumor Staging of Breast Cancer: Digital Mammography versus Digital Mammography Plus Tomosynthesis.

Background Combined digital mammography (DM) and digital breast tomosynthesis (DBT) (hereafter, DM plus DBT) has increased cancer detection rates when compared with those achieved with DM-only screening. However, there is limited literature on DBT as an adjunct to mammography in the staging of known breast cancers. Purpose To compare the diagnostic accuracy of DM alone with that of DM plus DBT in the identification of additional ipsilateral and contralateral lesions in women with newly diagnosed breast cancer.

Patient care for postamputation pain and the complexity of therapies: living experiences.

Aim: Limb amputation traumatically alters body image. Sensations rapidly prevail that the limb is still present and 85% of patients portray phantom limb pain. Throughout the testimonies of amputated patients with intense phantom limb pain, we show the difficulty in treating this chronic pain with current pharmacological and nonpharmacological therapies.

Transcarotid transcatheter aortic valve implantation: multicentre experience in France.

Objectives: Transcatheter aortic valve implantation is a well-recognized treatment option for high-risk patients with aortic stenosis. The femoral approach is possible in 80% of cases and remains the access of choice. When this approach is not feasible, other alternative routes have been proposed such as transapical, transaortic and subclavian.

Investigation of the predictive validity of laser-EPs in normal, UVB-inflamed and capsaicin-irritated skin with four analgesic compounds in healthy volunteers.

Aims: The aim of the present study was to assess the predictivity of laser-(radiant-heat)-evoked potentials (LEPs) from the vertex electroencephalogram, using an algesimetric procedure, testing the anti-nociceptive/anti-hyperalgesic effects of single oral doses of four marketed analgesics (of different compound classes) vs. placebo, in healthy volunteers with three skin types.

Methods: This was a randomized, placebo-controlled, single-blind, five-way-crossover trial.

Moderate Hypothermia Improves Cardiac and Vascular Function in a Pig Model of Ischemic Cardiogenic Shock Treated With Veno-Arterial ECMO.

Cardiogenic shock (CS) patients treated with extracorporeal membrane oxygenation (ECMO) have severe cardiac failure, associated with ischemia-reperfusion. The use of moderate hypothermia during ischemia-reperfusion syndrome is supported by experimental data. We therefore studied the effects of moderate hypothermia on cardiac and vascular function in pig ischemic CS treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO).

Transcarotid transcatheter aortic valve implantation.

Transcatheter aortic valve implantation is a well-recognized treatment option for high-risk patients with aortic stenosis. The femoral approach is possible in 80% of cases. Initially, only the transcarotid and subclavian approaches were performed as alternative routes.

The in situ gas-phase formation of a C-glycoside ion obtained during electrospray ionization tandem mass spectrometry. A unique intramolecular mechanism involving an ion-molecule reaction.

Rationale: This study examines the electrospray ionization mass spectrometry (ESI-MS), in-source collision-induced dissociation (CID) fragmentation and low-energy collision-induced dissociation tandem mass spectrometry (CID-MS/MS) of a synthetic pair of β- and α-anomers of the amphiphilic cholesteryl polyethoxy neoglycolipids containing the 2-azido-2-deoxy-D-galactosyl-D-GalN3 moiety. We describe the novel and unique in situ gas-phase formation of a C-glycoside ion formed during all these gas-phase processes and propose a reasonable mechanism for its formation.

Methods: The synthetic amphiphilic glycolipids were composed of the 2-deoxy-2-azido-D-galactosyl moiety (GalN3, the hydrophilic part) covalently attached to a polyethoxy spacer which is covalently linked to the cholesteryl moiety (hydrophobic part).

Ultrasound-guided high-intensity focused ultrasound treatment of breast fibroadenoma-a multicenter experience.

Background: The aim of our multicenter study was to assess the clinical outcome and safety of ultrasound (US)-guided high-intensity focused ultrasound (HIFU) in patients with breast fibroadenoma (FA).

Methods: From May 2011 to February 2013, 42 women with 51 FA in one or both breasts were selected for treatment with US-guided HIFU. Eight of 51 FA were treated twice.

Biological and biochemical properties of two Xenopus laevis N-acetylgalactosaminyltransferases with contrasting roles in embryogenesis.

The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. Until now, the mammalian forms of these enzymes have been the best characterized. However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-β/BMP signaling in embryogenesis.

Investigation of combined CYP3A4 inductive/inhibitory properties by studying statin interactions: a model study with the renin inhibitor ACT-178882.

Purpose: ACT-178882, a direct renin inhibitor, was used as a model compound in an elaborate drug-drug interaction study with atorvastatin and simvastatin to explore complex CYP3A4 inductive and inhibitory properties.

Methods: Thirty-two healthy male subjects received single doses of 20 mg atorvastatin and 20 mg simvastatin on days 1, 9, 31, and 41. On days 6 to 33, 500 mg ACT-178882 was administered once daily.

3D-fection: cell transfection within 3D scaffolds and hydrogels.

Background: 3D matrices are widely used as cell growth supports in basic research, regenerative medicine or cell-based drug assays. In order to genetically manipulate cells cultured within 3D matrices, two novel non-viral transfection reagents allowing preparation of matrices for in situ cell transfection were evaluated.

Results: Two lipidic formulations, 3D-Fect™ and 3D-FectIN™, were assessed for their ability to transfect cells cultured within 3D solid scaffolds and 3D hydrogels, respectively.

Relative bioavailability of a newly developed pediatric formulation of bosentan vs. the adult formulation.

What Is Known: Bosentan is a dual endothelin receptor antagonist approved for the treatment of pulmonary arterial hypertension (PAH). Since bosentan is frequently used to treat pediatric PAH patients, a pediatric formulation was developed.

Aim: To evaluate the pharmacokinetic properties of bosentan and its active metabolite, Ro 48-5033, of the quadrisected, dispersible pediatric vs.

Effect of Multiple-Dose Diltiazem on the Pharmacokinetics of the Renin Inhibitor ACT-077825.

This open-label, randomized study evaluated the effects of steady-state diltiazem on the pharmacokinetic, safety, and tolerability profile of a single dose of the novel renin inhibitor ACT-077825. Twelve healthy Caucasian male subjects (20-50 years) received in treatment sequence A, a single dose of 100 mg ACT-077825 (Days 1 and 17), and oral diltiazem 300 mg once daily (Days 14-26). In treatment sequence B, subjects received a single dose of 100 mg ACT-077825 (Days 4 and 22) and oral diltiazem 300 mg once daily (Days 1-13).

Comparative pharmacokinetic, pharmacodynamic, safety, and tolerability profiles of 3 different formulations of epoprostenol sodium for injection in healthy men.

Background: Epoprostenol sodium for injection is approved for the treatment of severe cases of primary pulmonary arterial hypertension. Currently, there are 3 approved formulations of this drug containing the same active ingredient (epoprostenol sodium) but differing with regard to excipients. When compared with epoprostenol sodium formulated with glycine-mannitol (epoprostenol GM), 2 new formulations of epoprostenol sodium, one formulated with arginine-mannitol (epoprostenol AM) and one formulated with arginine-sucrose (epoprostenol AS), have improved stability after reconstitution and dilution.

Drug-drug interaction study of ACT-178882, a new renin inhibitor, and diltiazem in healthy subjects.

Background And Objective: The cytochrome P450 (CYP) enzyme, CYP3A4, metabolizes ACT-178882, a new direct renin inhibitor. This study investigated the effect of diltiazem, a moderate inhibitor of CYP3A4, on the single-dose pharmacokinetics of ACT-178882 in healthy subjects.

Methods: In this open-label, two-way crossover, drug-drug interaction study, healthy young male subjects received treatments A and B in a randomized fashion.

Use of the model for end-stage liver disease score for guiding clinical decision-making in the selection of patients for emergency cardiac transplantation.

Objectives: The outcomes of emergency cardiac transplantation remain controversial, but recipient selection is essential for success. With a shortage of organs, it is essential to determine an objective method, such as a risk score, for choosing patients who are at too great a risk to undergo cardiac transplantation. In this study, we analysed the model for end-stage liver disease in terms of predicting operative mortality after emergency cardiac transplantation.

Age and sex effects on the single- and multiple-dose safety and pharmacokinetics of the new renin inhibitor ACT-178882.

Aim: To investigate the effect of age and sex on the single- and multiple-dose safety and pharmacokinetics of ACT-178882, a new direct renin inhibitor.

Methods: In the single-dose, open-label part of the study, healthy young and elderly male and female subjects received a dose of 300 mg ACT-178882. In the multiple-dose, double-blind, placebo-controlled part of the study, healthy elderly male and female subjects received ACT-178882 (300 or 600 mg) or placebo once-a-day for 14 days.

Pharmacokinetics, pharmacodynamics, and tolerability of ACT-077825, a new direct renin inhibitor after multiple-ascending doses in healthy subjects.

This study was conducted to characterize the multiple-dose tolerability, pharmacokinetics, and pharmacodynamics of ACT-077825, a new direct renin inhibitor, in healthy male subjects. In this single-center, double-blind, placebo-controlled, active-controlled (20 mg of enalapril), randomized multiple-ascending dose study, ACT-077825 was administered once a day. for 7 days in the 50-1000 mg dose range to sodium- and potassium-restricted subjects.

Clinical pharmacology of single- and multiple-ascending doses of ACT-178882, a new direct renin inhibitor, and its pharmacokinetic interaction with food and midazolam.

This study investigated the tolerability, safety, pharmacokinetics, and pharmacodynamics of ACT-178882, a new direct renin inhibitor, as well as its interaction with food and midazolam. Healthy male subjects received either single (10-1000 mg) or multiple doses (30-600 mg) administered once daily for 14 days of ACT-178882, placebo, or 20 mg enalapril in the fasted state. Following a 2-week washout, the single dose of 30 mg ACT-178882 was also administered in the fed state.

Determination of 6-keto prostaglandin F1α and its metabolites in human plasma by LC-MS/MS.

An HPLC-MS/MS method was developed and validated for the quantification of 6-keto prostaglandin F1α, the stable hydrolysis product of prostacyclin, and its metabolites 2,3-dinor-6-keto prostaglandin F1α and 6,15-diketo-13,14-dihydro prostaglandin F1α in human plasma. For sample preparation, a solid phase extraction step was combined with a column switching approach for analytes enrichment and further sample clean-up of the processed sample. The assay was validated in the concentration range 50.

Integrated pharmacokinetics and pharmacodynamics of epoprostenol in healthy subjects.

Aim: The aim of the study was to report the first thorough characterization of the pharmacokinetics (PK) and pharmacodynamics (PD) of epoprostenol in an integrated manner.

Method: Twenty healthy male subjects received two formulations of i.v.

Entry-into-humans study with a new direct renin inhibitor.

Purpose: To evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of escalating single oral doses of ACT-077825, a novel orally active renin inhibitor, in healthy male subjects.

Methods: In this single-center, double-blind, placebo- and active-controlled (with enalapril) randomized study, 70 subjects received a single dose of ACT-077825 (1-1,000 mg), placebo, or enalapril 20 mg under fasted conditions. The main pharmacokinetic endpoints were area under the plasma ACT-077825 concentration-time curve from time zero to infinity and the terminal half-life (t(1/2)).