A disease-associated gene desert directs macrophage inflammation through ETS2.

Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22-which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu's arteritis3-6-we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.

Infrared thermotransmittance-based temperature field measurements in semitransparent media.

Contactless temperature field measurements in or at the surfaces of semitransparent media are a scientific challenge as classical thermography techniques based on proper material emission cannot be used. In this work, an alternative method using infrared thermotransmittance for contactless temperature imaging is proposed. To overcome the weakness of the measured signal, a lock-in acquisition chain is developed and an imaging demodulation technique is used to retrieve the phase and amplitude of the thermotransmitted signal. These measurements, combined with an analytical model, enable the estimation of the thermal diffusivity and conductivity of an infrared semitransparent insulator (wafer of Borofloat 33 glass) and the monochromatic thermotransmittance coefficient at 3.3 µm. The obtained temperature fields are in good agreement with the model, and a detection limit of ±2 °C is estimated with this method. The results of this work open new opportunities in the development of advanced thermal metrology for semitransparent media.

[Intra-articular distal radial fracture with lunate fossa rotated, about 4 cases: interest of surgical procedure by volar medial approach]. / Fracture articulaire du radius distal avec fragment de fossette lunarienne retourné, à propos de 4 cas : intérêt du traitement chirurgical par voie antéro-médiale.

INTRODUCTION: Intra-articular distal radial fractures in young subjects occur in severe trauma. Articular reduction needs to be anatomical. We report four cases with the particularity of having a 90° or 180° rotated lunate fossa. Our goal is to bring out the positive aspects of surgical procedure by volar medial approach and to assess long-term functionnal and radiological results. MATERIAL AND METHODS: Our study focused on four men whose average age was 27 (age range from 19 to 43). The fractures were type IV according to Melone's classification. The associated lesions included: one fracture of the base of the ulnar styloid, one fracture of the distal quarter of the ulnar diaphysis and one scapho-lunate diastasis. We used a volar medial approach between the flexors tendons and the ulnar bundle in order to pin the fragment of lunate fossa. The rest of the radial epiphysis was pinned after a 5mm skin incision. In two cases, this pinning was complemented with a brachial-antebrachial-palmar cast and in the other two cases with an external fixator. RESULTS: The follow-up period averaged 68.8 (18 to 115) months, all the patients were clinically examined through antero-posterior, lateral and dynamic X-rays. The objective results assessed according to Green and O'Brien's criteria, later modified by Cooney, were as follows: two very good, one good, one average. The X-rays showed consolidated fractures. According to Knirk and Jupiter's classification of arthritis, we had three grades 0, one of which showed a subchondral sclerosis of the lunate fossa, and one grade 3. DISCUSSION AND CONCLUSION: Imaging with simple radiographs is not sufficient and needs to be complemented with CT scan. Our approach allows for direct access to the fragment of the lunate fossa and easier visualization of the distal radioulnar, compared to Henry's approach, thereby avoiding excessive traction of the median nerve. TYPE D'ÉTUDE: Niveau IV.

Effect of collagen hydrolysate in articular pain: a 6-month randomized, double-blind, placebo controlled study.

OBJECTIVE: Evaluation of the efficacy and safety of a food supplement made of collagen hydrolysate 1200 mg/day versus placebo during 6 months, in subjects with joint pain at the lower or upper limbs or at the lumbar spine. DESIGN: Comparative double-blind randomized multicenter study in parallel groups. SETTING: 200 patients of both genders of at least 50 years old with joint pain assessed as ≥30 mm on a visual analogical scale (VAS). INTERVENTION: Collagen hydrolysate 1200 mg/day or placebo during 6 months. MAIN OUTCOME MEASURE: Comparison of the percentage of clinical responder between the active collagen hydrolysate group and the placebo group after 6 months of study. A responder subject was defined as a subject experiencing a clinically significant improvement (i.e. by 20% or more) in the most painful joint using the VAS score. All analyses were performed using an intent-to-treat procedure. RESULTS: At 6 months, the proportion of clinical responders to the treatment, according to VAS scores, was significantly higher in the collagen hydrolysate (CH) group 51.6%, compared to the placebo group 36.5% (p<0.05). However, there was no significant difference between groups at 3 months (44.1% vs. 39.6%, p=0.53). No significant difference in terms of security and tolerability was observed between the two groups. CONCLUSIONS: This study suggests that collagen hydrolysate 1200 mg/day could increase the number of clinical responders (i.e. improvement of at least 20% on the VAS) compared to placebo. More studies are needed to confirm the clinical interest of this food supplement.