18 research outputs found
Ly6cLo non-classical monocytes promote resolution of rhesus rotavirus-mediated perinatal hepatic infammation
Perinatal hepatic inflammation can have devastating consequences. Monocytes play an important role in the initiation and resolution of inflammation, and their diverse functions can be attributed to specific cellular subsets: pro-inflammatory or classical monocytes (Ly6c(Hi)) and pro-reparative or non-classical monocytes (Ly6c(Lo)). We hypothesized that inherent differences in Ly6c(Hi) classical monocytes and Ly6c(Lo) non-classical monocytes determine susceptibility to perinatal hepatic inflammation in late gestation fetuses and neonates. We found an anti-inflammatory transcriptional profile expressed by Ly6c(Lo) non-classical monocytes, and a physiologic abundance of these cells in the late gestation fetal liver. Unlike neonatal pups, late gestation fetuses proved to be resistant to rhesus rotavirus (RRV) mediated liver inflammation. Furthermore, neonatal pups were rendered resistant to RRV-mediated liver injury when Ly6c(Lo) non-classical monocytes were expanded. Pharmacologic inhibition of Ly6c(Lo) non-classical monocytes in this setting restored susceptibility to RRV-mediated disease. These data demonstrate that Ly6c(Lo) monocytes promote resolution of perinatal liver inflammation in the late gestation fetus, where there is a physiologic expansion of non-classical monocytes, and in the neonatal liver upon experimental expansion of these cells. Therapeutic strategies directed towards enhancing Ly6c(Lo) non-classical monocyte function may mitigate the detrimental effects of perinatal liver inflammation
Association between promoter methylation of MLH1 and MSH2 and reactive oxygen species in oligozoospermic men—A pilot study
MLH1 and MSH2 are important genes for DNA mismatch repair and crossing over during
meiosis and are implicated in male infertility. Therefore, the methylation patterns
of the DNA mismatch repair genes MLH1 and MSH2 in oligozoospermic males were
investigated. Ten oligozoospermic patients and 29 normozoospermic donors were
analysed. Methylation profiles of the MLH1 and MSH2 promotors were analysed. In
addition, sperm motility and seminal reactive oxygen species (ROS) were recorded.
Receiver operating characteristic (ROC) analysis was conducted to determine the accuracy
of the DNA methylation status of MLH1 and MSH2 to distinguish between oligozoospermic
and normozoospermic men. In oligozoospermic men, MLH1 was
significantly (p = .0013) more methylated compared to normozoospermic men.
Additionally, there was a significant positive association (r = .384; p = .0159) between
seminal ROS levels and MLH1 methylation. Contrary, no association between MSH2
methylation and oligozoospermia was found. ROC curve analysis for methylation status
of MLH1 was significant (p = .0275) with an area under the curve of 61.1%, a sensitivity
of 22.2% and a specificity of 100.0%. This pilot study indicates oligozoospermic
patients have more methylation of MLH1 than normozoospermic patients. Whether
hypermethylation of the MLH1 promoter plays a role in repairing relevant mismatches
of sperm DNA strands in idiopathic oligozoospermia warrants further investigation
Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?
A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when “at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication.” The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist
Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders
For patients with psychiatric illnesses remaining refractory to 'standard' therapies, neurosurgical procedures may be considered. Guidelines for safe and ethical conduct of such procedures have previously and independently been proposed by various local and regional expert groups
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Ly6cLo non-classical monocytes promote resolution of rhesus rotavirus-mediated perinatal hepatic inflammation.
Perinatal hepatic inflammation can have devastating consequences. Monocytes play an important role in the initiation and resolution of inflammation, and their diverse functions can be attributed to specific cellular subsets: pro-inflammatory or classical monocytes (Ly6cHi) and pro-reparative or non-classical monocytes (Ly6cLo). We hypothesized that inherent differences in Ly6cHi classical monocytes and Ly6cLo non-classical monocytes determine susceptibility to perinatal hepatic inflammation in late gestation fetuses and neonates. We found an anti-inflammatory transcriptional profile expressed by Ly6cLo non-classical monocytes, and a physiologic abundance of these cells in the late gestation fetal liver. Unlike neonatal pups, late gestation fetuses proved to be resistant to rhesus rotavirus (RRV) mediated liver inflammation. Furthermore, neonatal pups were rendered resistant to RRV-mediated liver injury when Ly6cLo non-classical monocytes were expanded. Pharmacologic inhibition of Ly6cLo non-classical monocytes in this setting restored susceptibility to RRV-mediated disease. These data demonstrate that Ly6cLo monocytes promote resolution of perinatal liver inflammation in the late gestation fetus, where there is a physiologic expansion of non-classical monocytes, and in the neonatal liver upon experimental expansion of these cells. Therapeutic strategies directed towards enhancing Ly6cLo non-classical monocyte function may mitigate the detrimental effects of perinatal liver inflammation
Ly6cLo non-classical monocytes promote resolution of rhesus rotavirus-mediated perinatal hepatic inflammation.
Perinatal hepatic inflammation can have devastating consequences. Monocytes play an important role in the initiation and resolution of inflammation, and their diverse functions can be attributed to specific cellular subsets: pro-inflammatory or classical monocytes (Ly6cHi) and pro-reparative or non-classical monocytes (Ly6cLo). We hypothesized that inherent differences in Ly6cHi classical monocytes and Ly6cLo non-classical monocytes determine susceptibility to perinatal hepatic inflammation in late gestation fetuses and neonates. We found an anti-inflammatory transcriptional profile expressed by Ly6cLo non-classical monocytes, and a physiologic abundance of these cells in the late gestation fetal liver. Unlike neonatal pups, late gestation fetuses proved to be resistant to rhesus rotavirus (RRV) mediated liver inflammation. Furthermore, neonatal pups were rendered resistant to RRV-mediated liver injury when Ly6cLo non-classical monocytes were expanded. Pharmacologic inhibition of Ly6cLo non-classical monocytes in this setting restored susceptibility to RRV-mediated disease. These data demonstrate that Ly6cLo monocytes promote resolution of perinatal liver inflammation in the late gestation fetus, where there is a physiologic expansion of non-classical monocytes, and in the neonatal liver upon experimental expansion of these cells. Therapeutic strategies directed towards enhancing Ly6cLo non-classical monocyte function may mitigate the detrimental effects of perinatal liver inflammation