Retinoid X receptor α downregulation is required for tail and caudal spinal cord regeneration in the adult newt

Some adult vertebrate species,such as newts,axolotls and zebrafish,have the ability to regenerate their central nervous system（CNS）.However,the factors that establish a permissive CNS environment for correct morphological and functional regeneration in these species are not well understood.Recent evidence supports a role for retinoid signaling in the intrinsic ability of neurons,in these regeneration-competent species,to regrow after CNS injury.Previously,we demonstrated that a specific retinoic acid receptor（RAR）subtype,RARβ,mediates the effects of endogenous retinoic acid（RA）on neuronal growth and guidance in the adult newt CNS after injury.Here,we now examine the expression of the retinoid X receptor RXRα（a potential heterodimeric transcriptional regulator with RARβ）,in newt tail and spinal cord regeneration.We show that at 21 days post-amputation（dpa）,RXRαis expressed at temporally distinct periods and in non-overlapping spatial domains compared to RARβ.Whereas RARβprotein levels increase,RXRαproteins level decrease by 21 dpa.A selective agonist for RXR,SR11237,prevents both this downregulation of RXRαand upregulation of RARβand inhibits tail and caudal spinal cord regeneration.Moreover,treatment with a selective antagonist for RARβ,LE135,inhibits regeneration with the same morphological consequences as treatment with SR11237.Interestingly,LE135 treatment also inhibits the normal downregulation of RXRαin tail and spinal cord tissues at 21 dpa.These results reveal a previously unidentified,indirect regulatory feedback loop between these two receptor subtypes in regulating the regeneration of tail and spinal cord tissues in this regeneration-competent newt.

Treatment of Fracture Dislocation of the Femoral Head in a Resource Limited Country (Burundi)

Introduction: Fractures of the femoral head are rare injuries which generally follow a traumatic dislocation of the hip or in a poly-trauma scenario. A fracture dislocation of the femoral head is an orthopedic emergency. The most frequent complications after a fracture of the femoral head are osteonecrosis, post traumatic arthritis and heterotopic ossification. Objective: To focus on the therapeutic aspect of fracture-dislocations of femoral head and their short- and long-term prognoses. Materials and Methods: This is a prospective study conducted at Kamenge teaching hospital and Rohero Christian medical and surgical clinic from January 2013 to August 2020. All patients diagnosed with fracture-dislocations of the femoral head were included in this study. Results: Five patients were admitted for fracture dislocation of the femoral head. The mean age was 40.4 years and varied between 25 and 55 years. The dashboard injury was the most common mechanism and was found in four patients (80%). A standard x-ray was performed for the five patients as well as CT scans in two cases. All patients had posterior iliac dislocations with fractures of the femoral head classified as Pipkin I in three patients and Pipkin III in two patients. Closed reduction under general anesthesia within six hours was possible in one among the five patients and within 12 hours in two patients. These three cases were managed with open reduction and internal fixation (ORIF) via anterior approach with screw fixation of the femoral head fragment. In the two remaining patients reduction was not possible and for one of them there was a femoral neck fracture following closed manipulation, making the fracture Pipkin III. The two patients with Pipkin III injuries were managed with total hip replacement. With an average follow up of five years, standard x-rays of the three patients who had ORIF showed fracture union without avascular necrosis, posttraumatic arthritis or heterotopic ossification. The functional results for the five patients with an average follow up of four years were very good (3/5) and good (2/5). Conclusion: The diagnosis of fracture dislocations of the femoral head was based on clinical, radiographic and computed tomography criteria. Early reduction and internal fixation can restore the natural anatomy of the hip joint, especially in young adults with a good long-term prognosis. Sometimes total hip replacement is necessary for management of fracture dislocations of the femoral head.