Heterogeneity of neurons reprogrammed from spinal cord astrocytes by the proneural factors Ascl1 and Neurogenin2.

Astrocytes are a viable source for generating new neurons via direct conversion. However, little is known about the neurogenic cascades triggered in astrocytes from different regions of the CNS. Here, we examine the transcriptome induced by the proneural factors Ascl1 and Neurog2 in spinal cord-derived astrocytes in vitro. Each factor initially elicits different neurogenic programs that later converge to a V2 interneuron-like state. Intriguingly, patch sequencing (patch-seq) shows no overall correlation between functional properties and the transcriptome of the heterogenous induced neurons, except for K-channels. For example, some neurons with fully mature electrophysiological properties still express astrocyte genes, thus calling for careful molecular and functional analysis. Comparing the transcriptomes of spinal cord- and cerebral-cortex-derived astrocytes reveals profound differences, including developmental patterning cues maintained in vitro. These relate to the distinct neuronal identity elicited by Ascl1 and Neurog2 reflecting their developmental functions in subtype specification of the respective CNS region

Rofecoxib inhibits heterotopic ossification after total hip arthroplasty.

Contains fulltext : 53392.pdf (publisher's version ) (Closed access)INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) prevent heterotopic ossification but gastrointestinal complaints are frequently. Selective cyclooxygenase-2 (COX-2) inhibiting NSAID produce less gastrointestinal side effects. PATIENTS AND METHODS: A prospective two-stage study design for phase 2 clinical trials with 42 patients was used to determine if rofecoxib (a COX-2 inhibitor) 50 mg oral for 7 days prevents heterotopic ossification. A cemented primary THA was inserted for osteoarthroses. After 6 months heterotopic bone formation was assessed on AP radiographs using the Brooker classification. RESULTS: No heterotopic ossification was found in 81% of the patients, 19% of the patients had Brooker grade 1 ossification. CONCLUSION: Using a two-stage study design for phase 2 clinical trials, a 7-day treatment of a COX-2 inhibitor (rofecoxib) prevents effectively the formation of heterotopic ossification after cemented primary total hip arthroplasty

Prevention of heterotopic ossification in high-risk patients with total hip arthroplasty: the experience of a combined therapeutic protocol

The combination of radiotherapy and indomethacin for the prevention of heterotopic ossification (HO) in high-risk patients undergoing total hip arthroplasty (THA) has not been reported. The aim of the present study was to present the experience of our department with this combined therapeutic protocol. Fifty-four patients who underwent THA received a single dose of 7 Gy of postoperative radiotherapy and 75 mg of indomethacin for 15 days. Patients were analyzed for clinical and radiographical evidence of HO development at 1 year postoperatively. The overall radiographical incidence of HO was 20.4% (95% CI 10.6–33.5%), while only 1 patient with clinically significant HO was seen. Patients with secondary arthritis due to congenital hip disease had a statistically significantly higher incidence of HO compared with those with osteoarthrosis. The clinical assessment with the Merle d’Aubigné score showed that patients with radiographic documentation of HO had a lower mean score compared with those with no evidence of HO. No treatment-related side effects were seen. Combined radiotherapy and indomethacin was effective in preventing heterotopic ossification after total hip arthroplasty. The evaluation of this efficacy compared with radiotherapy or NSAIDs alone should be the future target of larger randomized designs