Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

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Glucocortiocoid Treatment of MCMV Infected Newborn Mice Attenuates CNS Inflammation and Limits Deficits in Cerebellar Development

Infection of the developing fetus with human cytomegalovirus (HCMV) is a major cause of central nervous system disease in infants and children; however, mechanism(s) of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV) results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC) proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ) in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV

SHARP VERSUS BLUNT DIALYSIS NEEDLE USE WITH BUTTONHOLE METHOD: OPEN RANDOMISED TRIAL

BACKGROUND: Current protocols recommend the use of a blunt needle to access the arteriovenous fistula via a buttonhole. This study aims to demonstrate whether a sharp needle can be used at the same buttonhole site without causing complications. GOAL: To measure and compare fistula cannulation failures between the use of blunt and sharp needles. PLAN: Open-crossover randomised controlled trial. PARTICIPANTS: Adult out-patients who had provided consent and were on dialysis with a mature arteriovenous fistula and buttonhole cannulation. OUTCOME MEASURES: Failed cannulation-difficulty in inserting the needle and the trampoline effect; incidence of complications, such as infection and haematomas; times to haemostasis; patients' pain; and patients' preferences. RESULTS: Based on analysis of the data from the 35 patients enrolled, no significant differences were detected in failed cannulation of the fistulae between the use of a blunt needle and a sharp needle for the 335 venous accesses (p = 0.071). However, a significant difference was detected for the 335 arterial accesses (p = 0.001), in which the sharp needle was more effective. Significant differences were also detected in the difficulty of insertion and in the trampoline effect for both venous and arterial access (p < 0.05); the use of a sharp needle was more favourable. CONCLUSION: This study demonstrates an increased incidence of failed cannulation using a blunt needle compared with using a sharp needle, although this was not significant. In addition, the use of a sharp needle did not result in any increase in complications