Medical pathways of children with juvenile idiopathic arthritis before referral to pediatric rheumatology centers.

Objective: A better understanding about the referral pathway of patients suffering from juvenile idiopathic arthritis (JIA) is required The aim of this study was to describe and analyze time from onset of symptoms to first pediatric rheumatology (PR) visit and the referral pathway of children with incident JIA in two French competence centers.

Methods: From October 2009 to October 2017, new JIA patients were registered in the "Auvergne-Loire cohort on JIA". We collected referral pathway, symptom onset, biological and clinical data at first assessment in PR department.

Filling the drug discovery gap: is high-content screening the missing link?

In recent years, questions about the sustainability of the current drug discovery process have triggered a revival of interest in phenotypic drug discovery approaches. This trend has clearly been amplified by the emergence of multiple cell-based assay technologies enabling a higher degree of translatability between in vitro conditions and physio-pathological situations, including induced pluripotent stem cells, three-dimensional models, co-culture and organ-on-a-chip systems, complemented by advances in gene editing technologies. Progress in High-Content Screening technology has also contributed to the recent excitement for phenotypic drug discovery approaches, bringing image-capture and processing, and data-analysis, to a level of content and throughput fully compatible with large scale drug discovery efforts.

Late effects after hematopoietic stem cell transplantation for β-thalassemia major: the French national experience.

In this retrospective study, we evaluate long-term complications in nearly all β-thalassemia-major patients who successfully received allogeneic hematopoietic stem cell transplantation in France. Ninety-nine patients were analyzed with a median age of 5.9 years at transplantation.

Using RNAi screening technologies to interrogate the extrinsic apoptosis pathway.

Despite the knowledge accumulated during the last two decades about programmed cell death, further investigations of the complex regulatory network of apoptosis, including the extrinsic pathways, are still needed to gain an exhaustive and comprehensive understanding of this critical biological process. In addition, the identification of novel modulators of apoptosis may represent a good opportunity for making new paths into an otherwise heavily investigated area, therefore providing a molecular basis for new therapeutic strategies. In the last decade, RNA interference has become the technology of choice for discovering genes that encode molecules with previously unknown functions in biological pathways of interest.

Challenges in developing bioanalytical assays for characterization of antibody-drug conjugates.

With more than 34 targets being investigated and nearly 20 clinical trials at various phases of development, antibody-drug conjugates (ADCs) hold a lot of promise for improving oncological malignancy therapy. This therapeutic strategy designed to specifically or preferentially deliver a cytotoxic agent to tumor cells through conjugation to a monoclonal antibody is not new. Although this approach is relatively simple conceptually, the history of ADCs clearly attests to the high degree of complexity in their development.

Congenital acute leukemia with initial indolent presentation--a case report.

Background: Congenital acute leukemia is a rare event, presenting usually as an aggressive disease with a poor prognosis. A differential diagnosis is the transient myeloproliferative disorder observed in Down syndrome. We describe the case of an apparently healthy newborn male child presenting with normal peripheral blood (PB) counts but with a blast population on differentials.

New insights into childhood autoimmune hemolytic anemia: a French national observational study of 265 children.

Background: Autoimmune hemolytic anemia is a rare condition in children. Little is known about its initial presentation and the subsequent progression of the disease.

Design And Methods: Since 2004, a national observational study has been aiming to thoroughly describe cases and identify prognostic factors.

Laparoscopic radical nephrectomy for unilateral renal cancer in children.

Purpose: At the present time, the standard approach for renal cancer in children is open surgery, and the role of laparoscopic approach remains to be defined. We report our preliminary experience in the treatment by laparoscopic radical nephrectomy (LRN) for unilateral renal cancer in children.

Methods: Five children, whose mean age was 4 years old, were operated for unilateral renal malignant tumors by laparoscopic approach in our unit from October 2005 to June 2007.

Light interception and partitioning between shoots in apple cultivars influenced by training.

The effect of two training systems (Central Leader with branch pruning versus Centrifugal Training with minimal pruning, i.e., removal of fruiting laterals only) on canopy structure and light interception was analyzed in three architecturally contrasting apple (Malus domestica Borkh.

Architecture of the pruned tree: impact of contrasted pruning procedures over 2 years on shoot demography and spatial distribution of leaf area in apple (Malus domestica).

Background And Aims: Demography and spatial distribution of shoots are rarely studied on pruned trees. The present 2-year study deals with the effect of pruning strategies on shoot demography and development, and consequences on the spatial distribution of leaf area in three architecturally contrasted - from type II to IV - apple cultivars: 'Scarletspur Delicious', 'Golden Delicious' and 'Granny Smith'.

Methods: All trees were initially subjected during 5 years to Central Leader training with winter heading on all long shoots.

Impact of TBI on late effects in children treated by megatherapy for Stage IV neuroblastoma. A study of the French Society of Pediatric oncology.

Purpose: To determine the contribution of total body irradiation (TBI) to late sequelae in children treated with high-dose chemotherapy and autologous bone marrow transplantation for Stage IV neuroblastoma.

Patients And Methods: We compared two populations that were similar with regard to age, stage, pre-autologous bone marrow transplantation chemotherapy (CT) regimen, period of treatment, and follow-up (12 years). The TBI group (n = 32) received TBI as part of the megatherapy procedure (1982-1993), whereas the CT group (n = 30) received conditioning without TBI (1985-1992).

Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia. Experience of the French Severe Chronic Neutropenia Study Group.

Background And Objectives: The two main complications of severe chronic neutropenia are fatal sepsis and myelodysplasia/acute leukemia (MDS/AL). Granulocyte colony-stimulating factor (G-CSF) therapy has significantly reduced the frequency and severity of infections, but its possible influence on the risk of malignancy is not known.

Design And Methods: The French Severe Chronic Neutropenia (SCN) Registry has prospectively collected data since 1994 on 231 patients with various forms of SCN, namely severe congenital neutropenia (n=101), cyclic neutropenia (n=60), glycogen storage disease type Ib (GSDIb) (n=15) and Shwachman-Diamond syndrome (SDS)(n=55).

Development of a frozen cell array as a high-throughput approach for cell-based analysis.

Recent advances in molecular biology, human genetics, and functional genomics tremendously increase the number of molecular targets available for potential therapeutic and diagnostic use. To complement DNA array data, cost-efficient high-throughput technologies providing reliable information at the protein level need to be developed. Here we describe the generation of a frozen cell array that required the use of single cell suspensions and could serve various applications such as the analysis of specific antibody or ligand binding to a large panel of different cell types.

Successful extracorporeal photochemotherapy for chronic graft-versus-host disease in pediatric patients.

A total of 254 extracorporeal photochemotherapy (ECP) procedures were performed in 8 children (median age 10 years; range 5-15) with extensive resistant chronic graft-versus-host disease (GVHD). ECP was carried out in the pediatric environment using a Cobe Spectra separator and UV-MATIC irradiator. A peripheral venous with a single-lumen permanent central catheter access (69% of ECP-apheresis) or a dual-lumen permanent central catheter access (26% of ECP-apheresis) were used preferentially.

Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity.

The fibroblast growth factors (FGFs), and the corresponding receptors, are implicated in more than just the regulation of epithelial cell proliferation and differentiation. Specifically, FGF23 is a regulator of serum inorganic phosphate levels, and mice deficient in FGF receptor-4 have altered cholesterol metabolism. The recently described FGF19 is unusual in that it is nonmitogenic and appears to interact only with FGF receptor-4.

Subduction of the Cocos plate in the Mid America Trench.

The Mid America Trench, off the Pacific coast of southern Mexico and central America, is the site of northeastward subduction of the Cocos oceanic plate under the North America and Caribbean plates (Fig. 1). In Guatemala, the North America and Caribbean plates are separated by the Polochic-Motagua left-lateral strike-slip faults (Fig.