Encouraging innovation activity: in the specific context of small- and medium-sized retailers

This paper aims at formalizing an innovation process well suited for small- and medium-sized enterprises (SMEs) specialized in retail. The design research consisted in analyzing conceptual models of innovation process from the literature and adapting it to the specific context. Indeed, the research issue deals with encouraging innovation activity in the context of small- and medium-sized retailers that have not yet integrated an intern design department. In the actual financial context, it is essential for SMEs to innovate in order to gain competitive advantage; but how to start a sized innovation activity? The undertaken research results in a plan that sets up a sized innovation activity gradually with a methodology conducting to repeated and regular new product development. Supported with international literature research, the paper contributes to the proposal of an innovation process meeting the two following requirements: - a retailer lacking knowledge in innovation activity and - an SME with limited financial means. From the industrial case studies that have been undertaken, an adapted process has been developed to ensure the success of innovation activity integration in this specific context

Mutant PRPF8 Causes Widespread Splicing Changes in Spliceosome Components in Retinitis Pigmentosa Patient iPSC-Derived RPE Cells

Retinitis pigmentosa; Alternative splicing; RNARetinitis pigmentosa; Empalme alternativo; ARNRetinitis pigmentària; Empalmament alternatiu; RNARetinitis pigmentosa (RP) is a rare, progressive disease that affects photoreceptors and retinal pigment epithelial (RPE) cells with blindness as a final outcome. Despite high medical and social impact, there is currently no therapeutic options to slow down the progression of or cure the disease. The development of effective therapies was largely hindered by high genetic heterogeneity, inaccessible disease tissue, and unfaithful model organisms. The fact that components of ubiquitously expressed splicing factors lead to the retina-specific disease is an additional intriguing question. Herein, we sought to correlate the retinal cell-type-specific disease phenotype with the splicing profile shown by a patient with autosomal recessive RP, caused by a mutation in pre-mRNA splicing factor 8 (PRPF8). In order to get insight into the role of PRPF8 in homeostasis and disease, we capitalize on the ability to generate patient-specific RPE cells and reveal differentially expressed genes unique to RPE cells. We found that spliceosomal complex and ribosomal functions are crucial in determining cell-type specificity through differential expression and alternative splicing (AS) and that PRPF8 mutation causes global changes in splice site selection and exon inclusion that particularly affect genes involved in these cellular functions. This finding corroborates the hypothesis that retinal tissue identity is conferred by a specific splicing program and identifies retinal AS events as a framework toward the design of novel therapeutic opportunities.This work was supported by Institute of Health Carlos III/ERDF (European Regional Development Fund), Spain [PI16/00409 (DL), PI20/01119 (DL), CP18/00033 (DL), PI15/00227 (MC), CPII16/00037 (SE), and PI18-00286 (SE)], Platform for Proteomics, Genotyping and Cell Lines; PRB3 of ISCIII (PT17/0019/0024); National Science Foundation GACR 18-04393S and the project “Centre of Reconstructive Neuroscience”, registration number CZ.02. 1.01/0.0./0.0/15_003/0000419PI15/00227; Spanish Ministry of Economy and Competitiveness grant BES-2016-076994 (ÁA-L); and Academy of Finland (HS)

STENOSE ISCHEMIQUE DU GRELE SECONDAIRE A UNE EMBOLIE DE CRISTAUX DE CHOLESTEROL (A PROPOS D'UN CAS ET REVUE DE LA LITTERATURE DES MANIFESTATIONS DIGESTIVES)

PARIS13-BU Serge Lebovici (930082101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Kidney transplantation during the COVID‐19 pandemic: Potential long‐term consequences of an early post‐transplant infection

International audienceRecently, Akalin et al.1 reported a 28% mortality among kidney‐transplant patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2). Two of the 10 patients who died had been transplanted within the previous 5 weeks. During the coronavirus disease (COVID)‐19 outbreak, kidney transplant programs were suspended in several countries2. Although the pandemic is still ongoing, the stop of lockdown has prompted several transplant centers to restart kidney transplantation programs. It is recommended to consider that donors and recipients are screened for SARS‐CoV‐2 before transplantation by means of nuclear acid tests with or without chest CT scans

Treatment of large plasma volumes using specific immunoadsorption to desensitize ABO-incompatible kidney-transplant candidates

Background: ABO-incompatible (ABOi) kidney-transplantation has very good long-term results, i.e. similar to those observed for living-kidney ABO-compatible transplantation. This is because patients are desensitized at pretransplant using apheresis and rituximab therapy, with tacrolimus-based immunosuppression. Objectives: To assess the efficacy of a single, pretransplant (Day –1), specific immunoadsorption session using Glycosorb® columns (anti-A or anti-B; Glycorex Sweden) to treat large volumes of plasma (up to 18 L). Patients and Methods: Prospective single-center study evaluating 12 consecutive patients (6 males), aged 40 (23–59) years. Incompatibilities were A into 0 (8), B into 0 (3), and AB into 0 (1). Pretransplant desensitization relied on rituximab (D–30), tacrolimus, mycophenolic acid, and steroids (all started on D–13), and a single session of specific immunoadsorption on D–1. Immunoadsorption was coupled in tandem with a hemodialysis session. Results: Overall, 15 L (11–18) of plasma were treated per patient, i.e., 0.2 (0.11–0.36 L/kg). Isoagglutinin titers were 1/16 (1/5–1/64) before the procedure, decreasing after 6 hours to 1/5 (1/1–1/16 P = 0.008), and to 1/2 (1/1–1/8; P = 0.05) at completion of the session. The next day, i.e., the day of transplantation, there was no rebound of isoagglutinins [1/4 (1/1–1/5); P = ns]. The procedure was well tolerated with no side-effects and no significant changes in hemoglobin level, platelet counts, fibrinogen, or albumin levels. Conclusions: For ABOi kidney-transplantation, a single, longer, specific immunoadsorption session was very efficient at 1-day pre-transplantation with no rebound. These results should be confirmed when isoagglutinin titers are higher (≥120)

Do anti‐IL‐6R blockers have a beneficial effect in the treatment of antibody‐mediated rejection resistant to standard therapy after kidney transplantation?

International audienceAntibody‐mediated rejection (AMR) that resists to standard of care (SOC) therapy remains a major challenge after kidney transplantation and leads to graft failure in a majority of cases. The use of anti‐IL6 receptor antibodies was suggested to treat chronic antibody‐mediated rejection (cAMR) after failure of classical treatments. We treated nine patients with AMR resistant to apheresis, rituximab, and intravenous immunoglobulins, with a monthly infusion of tocilizumab and compared them with a historical cohort of 37 patients with similar clinical, immunological, and histological characteristics. The 1‐year graft survival and the decline in renal function did not differ between patients who received tocilizumab and those who did not. Histological follow‐up showed that despite a decrease in inflammation and tubulitis scores after tocilizumab, the course of antibody‐mediated lesions and chronic glomerulopathy were similar in both groups. In our study, the addition of monthly infusions of tocilizumab did not alter the course of AMR that resist to SOC therapy. Large randomized studies are urgently needed to assess the effect of tocilizumab in this context