Notch signalling is linked to epidermal cell differentiation level in basal cell carcinoma, psoriasis and wound healing

BACKGROUND: Epidermal homeostasis involves the monitoring of continuous proliferative and differentiative processes as keratinocytes migrate from the basal layer to the skin surface. Recently, differentiation of epidermal stem cells was shown to be promoted by the Notch pathway. This pathway is characterised by cell-cell interactions between transmembrane proteins and was first implicated in lateral inhibition, patterning and cell binary choices during embryogenesis. METHODS: By in situ hybridisation, we investigated the in vivo expression of related genes, namely; Notch 1–3, Delta 1, Jagged 1, Lunatic Fringe, Radical Fringe and Manic Fringe during keratinocyte proliferation and differentiation in humans in basal cell carcinoma, psoriasis and in wound healing experiments, compared with normal adult skin. RESULTS: We show that the highest level of transcription of these genes is in the basal cell layer of non-lesional skin. Conversely, when keratinocytes were hyperproliferating, as in basal cell carcinoma, psoriasis, and during the first step of re-epithelialisation, expression was weak or non-existent. Furthermore, normal levels of transcripts were rescued in psoriatic plaques when treated by phototherapy, as well as in newly regenerated stratified epidermis following wound healing. CONCLUSION: The Notch signalling involved in the differentiation programme of normal adult human epidermis is altered under experimental conditions and pathologies which modify this programme

IRES complexity before IFN-alpha treatment and evolution of the viral load at the early stage of treatment in peripheral blood mononuclear cells from chronic hepatitis C patients.

In the proof, we asked to correct the name of one Author, and the adddess; this was acknowledged by the Editor, but was omitted in the final published version!International audienceAt the early stage of treatment, IFN alpha-2a induces inhibition of HCV replication. The viral load reflects mainly the degradation rate of the viruses. However, differences in the behavior of the viral population depend on changes, which occurred in the HCV-IRES genome. In this study, cloning and sequencing strategies permitted the generation of a large number of IRES sequences from the PBMCs of 18 patients (5 women, 13 men) with chronic hepatitis C. The HCV IRES appeared to be highly conserved structurally. However, some variability was found between the different isolates obtained: 467 substitutions with a median of 7 variants/patients. No relationship was observed between pre-treatment IRES complexity and the viral load at the beginning. However, on review of the evolution of viral load in the PBMCs during the first 3 days of IFN alpha-2a treatment, patients could be classified into two groups: Group 1, in which the viral population continued to replicate and Group 2, in which the viral load decreased significantly (P = 0.01727). Positioning of the mutations on the predicted IRES secondary structure showed that the distribution of the mutations and their apparition frequency were different between the two groups. At the early stage of treatment, IFN alpha-2a was efficient in reducing the viral replication in a significant number of patients; mechanisms of response might affect the virus directly. However, pre-treatment genomic variations observed in the 5'NCR of HCV were not a parameter of a later response to antiviral therapy in chronic hepatitis C patients. (244

Arthroscopic Bristow-Latarjet Combined With Bankart Repair Restores Shoulder Stability in Patients With Glenoid Bone Loss

BACKGROUND: Arthroscopic Bankart repair alone cannot restore shoulder stability in patients with glenoid bone loss involving more than 20% of the glenoid surface. Coracoid transposition to prevent recurrent shoulder dislocation according to Bristow-Latarjet is an efficient but controversial procedure. QUESTIONS/PURPOSES: We determined whether an arthroscopic Bristow-Latarjet procedure with concomitant Bankart repair (1) restored shoulder stability in this selected subgroup of patients, (2) without decreasing mobility, and (3) allowed patients to return to sports at preinjury level. We also evaluated (4) bone block positioning, healing, and arthritis and (5) risk factors for nonunion and coracoid screw pullout. METHODS: Between July 2007 and August 2010, 79 patients with recurrent anterior instability and bone loss of more than 20% of the glenoid underwent arthroscopic Bristow-Latarjet-Bankart repair; nine patients (11%) were either lost before 2-year followup or had incomplete data, leaving 70 patients available at a mean of 35 months. Postoperative radiographs and CT scans were evaluated for bone block positioning, healing, and arthritis. Any postoperative dislocation or any subjective complaint of occasional to frequent subluxation was considered a failure. Physical examination included ROM in both shoulders to enable comparison and instability signs (apprehension and relocation tests). Rowe and Walch-Duplay scores were obtained at each review. Patients were asked whether they were able to return to sports at the same level and practice forced overhead sports. Potential risk factors for nonhealing were assessed. RESULTS: At latest followup, 69 of 70 (98%) patients had a stable shoulder, external rotation with arm at the side was 9° less than the nonoperated side, and 58 (83%) returned to sports at preinjury level. On latest radiographs, 64 (91%) had no osteoarthritis, and bone block positioning was accurate, with 63 (90%) being below the equator and 65 (93%) flush to the glenoid surface. The coracoid graft healed in 51 (73%), it failed to unite in 14 (20%), and graft osteolysis was seen in five (7%). Bone block nonunion/migration did not compromise shoulder stability but was associated with persistent apprehension and less return to sports. Use of screws that were too short or overangulated, smoking, and age higher than 35 years were risk factors for nonunion. CONCLUSIONS: The arthroscopic Bristow-Latarjet procedure combined with Bankart repair for anterior instability with severe glenoid bone loss restored shoulder stability, maintained ROM, allowed return to sports at preinjury level, and had a low likelihood of arthritis. Adequate healing of the transferred coracoid process to the glenoid neck is an important factor for avoiding persistent anterior apprehension. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence

Arthroscopic Latarjet procedure with double-button fixation: short-term complications and learning curve analysis

BACKGROUND: The arthroscopic Latarjet with double-button fixation is a guided procedure recently proposed to treat anterior shoulder instability with glenoid bone loss. The goal of this study was to report intraoperative and early postoperative complications and to analyze the learning curve. METHODS: This was a prospective, nonrandomized study that included 88 patients. Intraoperative or postoperative complications as well as adverse events and operative time were recorded. Clinical outcomes were evaluated at 2 weeks, 1.5 months, and at the last follow-up. Radiologic analysis was based on an immediate postoperative computed tomography scan. RESULTS: The intraoperative complications or adverse events rate was 3.3%: 1 conversion to open surgery, 1 bone block fracture, and 1 instrumentation problem. The postoperative complication rate was 6.8%: 4 coracoid migrations, and 2 subluxations. None of these complications occurred beyond the 10th case performed. The average operative time significantly decreased with surgical experience (r = -0.8426; 95% confidence interval, -0.9074 to -0.7384; P < .0001) to reach 76 ± 12 minutes (range, 62-95 minutes) at 30 cases. Radiologically, 90% of the bone blocks were flush and subequatorial beyond the 30th case. At a mean follow-up of 12.6 months (range, 6-24 months), Walch-Duplay and Rowe scores were 80 and 81 points, respectively. CONCLUSIONS: At short-term follow-up, the arthroscopic Latarjet procedure with double-button fixation exhibited a low complication rate. Operative time significantly improved with surgical experience and was optimized after 30 cases. Early clinical results confirmed that this procedure can be safe and reliable

Question de priorité

Thélu L. Question de priorité. In: Manuel général de l'instruction primaire : journal hebdomadaire des instituteurs. 68e année, tome 37, 1901. pp. 247-248

Immune-competent in vitro co-culture models as an approach for skin sensitisation assessment

International audienceThere is a complex interplay between numerous cell types that act at different steps of the mechanism leading to allergic contact dermatitis. The validated in vitro methods for skin sensitisation assessment provide good statistical correspondence to local lymph node assay (LLNA) or to human data but, for the most part, poorly represent the actual in vivo situation as they generally involve single cell type culture in 2D. Significant progress has been made over the past decades to develop new technologies of data generation concurrently with novel approaches to improve the models especially by the use of co-culture. The importance of heterotypic cell-cell interactions in the in vitro assessment of skin sensitisation should not be overlooked. This review addresses the technical aspects to take into consideration when co-culturing depending on the desired objective and describes the different keratinocytes and dendritic cells co-cultures developed in 2D and 3D. To date, from a regulatory point of view, no alternative method to animal testing for skin sensitisation potential assessment using a keratinocytes and dendritic cells co-culture model is yet proposed. This review also presents several directions of further development

Hepatitis C virus whole genome sequencing: Current methods/issues and future challenges

International audienceTherapy for hepatitis C is currently undergoing a revolution. The arrival of new antiviral agents targeting viral proteins reinforces the need for a better knowledge of the viral strains infecting each patient. Hepatitis C virus (HCV) whole genome sequencing provides essential information for precise typing, study of the viral natural history or identification of resistance-associated variants. First performed with Sanger sequencing, the arrival of next-generation sequencing (NGS) has simplified the technical process and provided more detailed data on the nature and evolution of viral quasi-species. We will review the different techniques used for HCV complete genome sequencing and their applications, both before and after the apparition of NGS. The progress brought by new and future technologies will also be discussed, as well as the remaining difficulties, largely due to the genomic variability

SECEC Research Grant 2008 II: Use of platelet- and leucocyte-rich fibrin (L-PRF) does not affect late rotator cuff tendon healing: a prospective randomized controlled study.

BACKGROUND Because the retear rate after rotator cuff repairs remains high, methods to improve healing are very much needed. Platelet-rich concentrates have been shown to enhance tenocyte proliferation and promote extracellular matrix synthesis in vitro; however, their clinical benefit remains unclear. We hypothesized that arthroscopic rotator cuff repair with leucocyte- and platelet-rich fibrin (L-PRF) results in better clinical and radiographic outcome at 12 months of follow-up than without L-PRF. METHODS Thirty-five patients were randomized to receive arthroscopic rotator cuff repair with L-PRF locally applied to the repair site (L-PRF+ group, n = 17) or without L-PRF (L-PRF- group, n = 18). Preoperative and postoperative clinical evaluation included the Subjective Shoulder Value, visual analog score for pain, Simple Shoulder Test, and Constant-Murley score. The anatomic watertight healing, tendon thickness, and tendon quality was evaluated using magnetic resonance arthrography at 12 months of follow-up. RESULTS No complications were reported in either group. The mean Subjective Shoulder Value, Simple Shoulder Test, and Constant-Murley scores increased from preoperatively to postoperatively, showing no significant differences between the groups. Complete anatomic watertight healing was found in 11 of 17 in the L-PRF+ group and in 11 of 18 in the L-PRP- group (P = .73). The mean postoperative defect size (214 ± 130 mm(2) in the L-PRF+ group vs 161 ± 149 mm(2) in the L-PRF- group; P = .391) and the mean postoperative tendon quality according to Sugaya (L-PRF+ group: 3.0 ± 1.4, L-PRF- group: 3.0 ± 0.9) were similar in both groups at 12 months of follow-up. CONCLUSION Arthroscopic rotator cuff repair with application of L-PRF yields no beneficial effect in clinical outcome, anatomic healing rate, mean postoperative defect size, and tendon quality at 12 months of follow-up