[Measuring the intensity of restraint during care in children: Validation of the Pric scale].

Restraint is used relatively often during pediatric care. However, no scale has yet been validated to assess its intensity. The study presented here did this for the Procedural Restraint Intensity in Children tool in metrological terms (with some limitations).

An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGF blockade therapy.

Increasing evidence suggests that the presence and spatial localization and distribution pattern of tumor infiltrating lymphocytes (TILs) is associate with response to immunotherapies. Recent studies have identified TGF activity and signaling as a determinant of T cell exclusion in the tumor microenvironment and poor response to PD-1/PD-L1 blockade. Here we coupled the artificial intelligence (AI)-powered digital image analysis and gene expression profiling as an integrative approach to quantify distribution of TILs and characterize the associated TGF pathway activity.

SAR439859, a Novel Selective Estrogen Receptor Degrader (SERD), Demonstrates Effective and Broad Antitumor Activity in Wild-Type and Mutant ER-Positive Breast Cancer Models.

Primary treatment for estrogen receptor-positive (ER+) breast cancer is endocrine therapy. However, substantial evidence indicates a continued role for ER signaling in tumor progression. Selective estrogen receptor degraders (SERD), such as fulvestrant, induce effective ER signaling inhibition, although clinical studies with fulvestrant report insufficient blockade of ER signaling, possibly due to suboptimal pharmaceutical properties.

Translational strategy using multiple nuclear imaging biomarkers to evaluate target engagement and early therapeutic efficacy of SAR439859, a novel selective estrogen receptor degrader.

Purpose: Preclinical in vivo nuclear imaging of mice offers an enabling perspective to evaluate drug efficacy at optimal dose and schedule. In this study, we interrogated sufficient estrogen receptor occupancy and degradation for the selective estrogen receptor degrader (SERD) compound SAR439859 using molecular imaging and histological techniques.

Material And Methods: [F]FluoroEstradiol positron emission tomography (FES-PET), [F]FluoroDeoxyGlucose (FDG) PET, and [F]FluoroThymidine (FLT) PET were investigated as early pharmacodynamic, tumor metabolism, and tumor proliferation imaging biomarkers, respectively, in mice bearing subcutaneous MCF7-Y537S mutant ERα+ breast cancer model treated with the SERD agent SAR439859.

An Antibody-Drug Conjugate Targeting MUC1-Associated Carbohydrate CA6 Shows Promising Antitumor Activities.

Glycosylation is a complex multienzyme-related process that is frequently deregulated in cancer. Aberrant glycosylation can lead to the generation of novel tumor surface-specific glycotopes that can be targeted by antibodies. Murine DS6 mAb (muDS6) was generated from serous ovary adenocarcinoma immunization.

A simple tool to measure procedural restraint intensity in children: validation of the PRIC (Procedural Restraint Intensity in Children) scale.

Purpose: Restraint is often used when administering procedures to children. However, no metrologically scale to measure the restraint intensity had yet been validated. This study validated the metrological criteria of a scale measuring the restraint intensity, Procedural Restraint Intensity in Children (PRIC), used during procedures in children.

Discovery of (2S)-8-[(3R)-3-methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido[1,2-a]pyrimidin-6-one: a novel potent and selective inhibitor of Vps34 for the treatment of solid tumors.

Vps34 (the human class III phosphoinositide 3-kinase) is a lipid kinase involved in vesicle trafficking and autophagy and therefore constitutes an interesting target for cancer treatment. Because of the lack of specific Vps34 kinase inhibitors, we aimed to identify such compounds to further validate the role of this lipid kinase in cancer maintenance and progression. Herein, we report the discovery of a series of tetrahydropyrimidopyrimidinone derivatives.

A dose-escalation study of SAR3419, an anti-CD19 antibody maytansinoid conjugate, administered by intravenous infusion once weekly in patients with relapsed/refractory B-cell non-Hodgkin lymphoma.

Purpose: To determine recommended dose, dose-limiting toxicity, safety profile, pharmacokinetics, preliminary antitumor activity, and exploratory pharmacodynamics of SAR3419, an antibody-drug conjugate targeting CD19, administered alone by intravenous infusion weekly (qw), in a dose-escalation phase I study in patients with refractory/relapsed (R/R) non-Hodgkin lymphoma (NHL).

Experimental Design: Patients with R/R CD19(+) B-NHL were treated with escalating doses of SAR3419 repeated qw for eight to 12 doses. On the basis of clinical evidence of late or cumulative toxicities, the study protocol was amended to test an "optimized" administration schedule consisting of four qw doses followed by four biweekly (q2w) doses (qw/q2w) at the recommended dose with the intent of reducing drug accumulation.

SAR3419: an anti-CD19-Maytansinoid Immunoconjugate for the treatment of B-cell malignancies.

SAR3419 is a novel anti-CD19 humanized monoclonal antibody conjugated to a maytansine derivate through a cleavable linker for the treatment of B-cell malignancies. SAR3419 combines the strengths of a high-potency tubulin inhibitor and the exquisite B-cell selectivity of an anti-CD19 antibody. The internalization and processing of SAR3419, following its binding at the surface of CD19-positive human lymphoma cell lines and xenograft models, release active metabolites that trigger cell-cycle arrest and apoptosis, leading to cell death and tumor regression.

[Pain assessment in children by triage emergency nurses].

The assessment of pain in children in the paediatric emergency department is essential for high quality care. Recognizing pain is not enough: only the use of validated assessments tools enables staff to include pain on part of daily care. The objective analysis of care practices helps to improve the quality of care in children.

Local gene transfer and expression following intramuscular administration of FGF-1 plasmid DNA in patients with critical limb ischemia.

NV1FGF is an expression plasmid encoding sp.FGF-1(21-154) currently under investigation for therapeutic angiogenesis in clinical trials. NV1FGF plasmid distribution and transgene expression following intramuscular (IM) injection in patients is unknown.

Human FGF-1 gene transfer promotes the formation of collateral vessels and arterioles in ischemic muscles of hypercholesterolemic hamsters.

Background: Acidic fibroblast growth factor (FGF-1) has been identified as a potent mitogen for vascular cells, inducing formation of mature blood vessels in vitro and in vivo and represents one of the most promising approaches for the treatment of ischemic cardiovascular diseases by gene therapy. Nevertheless, and most probably due to the few experimental models able to address the issue, no study has described the therapeutic effects of FGF-1 gene transfer in subjects with peripheral arterial disease (PAD) exhibiting a clinically relevant cardiovascular pathology.

Methods: In order to assess the potency of FGF-1 gene transfer for therapeutic angiogenesis in ischemic skeletal muscles displaying decreased gene expression levels and sustained impaired formation of collateral vessels and arterioles, we developed a model of PAD in hamsters with a background of hypercholesterolemia.

Near wins prolong gambling on a video lottery terminal.

The purpose of the present study was to evaluate whether near wins can prolong gambling activity on a video lottery terminal. In a three-reel game, near wins were operationally defined as two identical symbols followed by a third different symbol. Players in an experimental condition were exposed to 27% near wins in a series of continuous losses, whereas players in a control group were exposed to none.

Erroneous verbalizations and risk taking at video lotteries.

This study examined the effect of erroneous perceptions verbalized by a game accomplice on participants' gambling. The sample consisted of 22 men and 10 women, aged 18 and older, who did not show excessive gambling problems, but who had played video lotteries at least once during the last 6 months. The participants were randomly assigned into one of three groups, where they gambled in the presence of an accomplice who verbalized three types of perceptions: (1) the accomplice emitted erroneous thoughts about gambling, (2) the accomplice verbalized adequate thoughts about gambling, or (3) the accomplice did not speak.

Efficient gene regulation by PPAR gamma and thiazolidinediones in skeletal muscle and heart.

We have developed a new gene regulation system for gene therapy. This system consists of two expression cassettes; one expresses the human peroxisome proliferator-activated receptor gamma(PPAR gamma), and the other expresses the therapeutic gene under the control of multiple peroxisome proliferator-activated receptor (PPAR) response elements (PPREs) linked to a basal promoter. Using direct injection of plasmid DNA into skeletal muscle or myocardium of rodents and oral administration of clinically approved PPAR gamma activators, we demonstrate that reporter gene expression can be induced more than 25-fold.

The use of direct cDNA selection to rapidly and effectively identify genes in the fungus Aspergillus fumigatus.

Aspergillus fumigatus is one of the causes of invasive lung disease in immunocompromised individuals. To rapidly identify genes in this fungus, including potential targets for chemotherapy, diagnostics, and vaccine development, we constructed cDNA libraries. We began with non-normalized libraries, then to improve this approach we constructed a normalized cDNA library using direct cDNA selection.