Long-Term Cultures of Spinal Cord Interneurons.

Spinal cord interneurons (SpINs) are highly diverse population of neurons that play a significant role in circuit reorganization and spontaneous recovery after spinal cord injury. Regeneration of SpIN axons across rodent spinal injuries has been demonstrated after modification of the environment and neurotrophin treatment, but development of methods to enhance the intrinsic regenerative ability of SpINs is needed. There is a lack of described in vitro models of spinal cord neurons in which to develop new regeneration treatments. For this reason, we developed a new model of mouse primary spinal cord neuronal culture in which to analyze maturation, morphology, physiology, connectivity and regeneration of identified interneurons. Isolated from E14 mice, the neurons mature over 15 days in vitro, demonstrated by expression of maturity markers, electrophysiological patch-clamp recordings, and formation of synapses. The neurons express markers of SpINs, including Tlx3, Lmx1b, Lbx1, Chx10, and Pax2. The neurons demonstrate distinct morphologies and some form perineuronal nets in long-term cultivation. Live neurons in various maturation stages were axotomized, using a 900 nm multiphoton laser and their fate was observed overnight. The percentage of axons that regenerated declined with neuronal maturity. This model of SpINs will be a valuable tool in future regenerative, developmental, and functional studies alongside existing models using cortical or hippocampal neurons

Juvenile Idiopathic Arthritis:Roma Children Seem to Run More Risk than Non-Roma

Background: Ethnic information regarding juvenile idiopathic arthritis (JIA) exists for various populations across the world but is fully lacking for Roma. We assessed the occurrence and clinical characteristics of JIA in Roma vs. non-Roma children. Methods: We obtained data on all outpatients (n = 142) from a paediatric rheumatology centre (age 3 to 18 years) in the eastern part of Slovakia (Kosice region). We assessed patients’ age, gender, disease type and related extra-articular conditions by ethnicity. We obtained population data from the 2011 census. Results: The share of Roma children was higher in the clinical JIA sample than in the overall population (24.6%, n = 35, Roma in the sample vs. 10.8%, n = 142, Roma in the population, p < 0.05). Moreover, Roma children had been diagnosed more frequently with extra-articular conditions but did not differ in other symptoms. Treatments also did not differ by ethnicity. Conclusion: Roma children had been diagnosed more with JIA than their non-Roma peers. This calls for further research on the causes of this increased disease burden in Roma children

Juvenile Idiopathic Arthritis: Roma Children Seem to Run More Risk than Non-Roma

Background: Ethnic information regarding juvenile idiopathic arthritis (JIA) exists for various populations across the world but is fully lacking for Roma. We assessed the occurrence and clinical characteristics of JIA in Roma vs. non-Roma children. Methods: We obtained data on all outpatients (n = 142) from a paediatric rheumatology centre (age 3 to 18 years) in the eastern part of Slovakia (Kosice region). We assessed patients' age, gender, disease type and related extra-articular conditions by ethnicity. We obtained population data from the 2011 census. Results: The share of Roma children was higher in the clinical JIA sample than in the overall population (24.6%, n = 35, Roma in the sample vs. 10.8%, n = 142, Roma in the population, p <0.05). Moreover, Roma children had been diagnosed more frequently with extra-articular conditions but did not differ in other symptoms. Treatments also did not differ by ethnicity. Conclusion: Roma children had been diagnosed more with JIA than their non-Roma peers. This calls for further research on the causes of this increased disease burden in Roma children

Involvement of mTOR Pathways in Recovery from Spinal Cord Injury by Modulation of Autophagy and Immune Response

Traumatic spinal cord injury (SCI) is untreatable and remains the leading cause of disability. Neuroprotection and recovery after SCI can be partially achieved by rapamycin (RAPA) treatment, an inhibitor of mTORC1, complex 1 of the mammalian target of rapamycin (mTOR) pathway. However, mechanisms regulated by the mTOR pathway are not only controlled by mTORC1, but also by a second mTOR complex (mTORC2). Second-generation inhibitor, pp242, inhibits both mTORC1 and mtORC2, which led us to explore its therapeutic potential after SCI and compare it to RAPA treatment. In a rat balloon-compression model of SCI, the effect of daily RAPA (5 mg/kg; IP) and pp242 (5 mg/kg; IP) treatment on inflammatory responses and autophagy was observed. We demonstrated inhibition of the mTOR pathway after SCI through analysis of p-S6, p-Akt, and p-4E-BP1 levels. Several proinflammatory cytokines were elevated in pp242-treated rats, while RAPA treatment led to a decrease in proinflammatory cytokines. Both RAPA and pp242 treatments caused an upregulation of LC3B and led to improved functional and structural recovery in acute SCI compared to the controls, however, a greater axonal sprouting was seen following RAPA treatment. These results suggest that dual mTOR inhibition by pp242 after SCI induces distinct mechanisms and leads to recovery somewhat inferior to that following RAPA treatment

Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee

Background To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies