Underwood Gregersen (testfemale92)

Cav2.2 N-type voltage-dependent Ca2+ channel (VDCC) expressed in neurons is known to be essential for neurotransmitter release. We have shown previously that this channel is also expressed in nonexcitable microglia and plays pivotal roles in microglial functions. Here, we have examined the effects of microglia-specific knockdown (KD) of Cav2.2 channel in a mouse model of Parkinson's disease (PD). We found that the KD of Cav2.2 channel reduces the accumulation of microglia in the substantia nigra and ameliorates the behavioral deficits in PD model mice. These results are in marked contrast with those found in microglia-specific KD of Cav1.2 L-type channel, where exacerbated symptoms are observed. Our results suggest that blockade of microglial Cav2.2 N-type VDCC is beneficial for the treatment of PD.Purpose High-dose-rate (HDR) brachytherapy is an established technique to be used as monotherapy option or focal boost in conjunction with external beam radiation therapy (EBRT) for treating prostate cancer. Radiation source path reconstruction is a critical procedure in HDR treatment planning. Manually identifying the source path is labor intensive and time inefficient. In recent years, magnetic resonance imaging (MRI) has become a valuable imaging modality for image-guided HDR prostate brachytherapy due to its superb soft-tissue contrast for target delineation and normal tissue contouring. The purpose of this study is to investigate a deep-learning-based method to automatically reconstruct multiple catheters in MRI for prostate cancer HDR brachytherapy treatment planning. Methods Attention gated U-Net incorporated with total variation (TV) regularization model was developed for multi-catheter segmentation in MRI. The attention gates were used to improve the accuracy of identifying small catheter points, whiror of less then 2.0 mm, while 63% were within 1.0 mm. Conclusions In this study, we proposed a novel multi-catheter detection method to precisely localize the tips and shafts of catheters in three-dimensional MRI images of HDR prostate brachytherapy. It paves the way for elevating the quality and outcome of MRI-guided HDR prostate brachytherapy.Inflammation represents an important factor leading to metabolic imbalance within the intervertebral disc (IVD), conducive to degenerative changes. Therefore, a thorough knowledge of the IVD and endplate (EP) cell behaviour in such pathological environments is essential when designing regenerative therapeutic strategies. The present study aimed at assessing the molecular response of the IVD constitutive nucleus pulposus (NPCs)-, annulus fibrosus (AFCs)- and endplate (EPCs)-derived cells to interleukin (IL)-1β treatment, through large-scale, high-throughput microarray and protein analysis, identifying the differentially expressed genes and released proteins. Overall, the inflammatory stimulus downregulated stemness genes while upregulating pro-inflammatory, pro-angiogenic and catabolic genes, including matrix metalloproteases, which were not balanced by a concomitant upregulation of their inhibitors. Upregulation of anti-inflammatory and anabolic tumour necrosis factor inducible gene 6 protein (TNFAIP6), of IL-1 receptor antagonist (IL-1Ra) (at gene and protein levels) and of trophic insulin-like growth factor 1 (IGF1) was also observed in all cell types; IGF1 particularly in AFCs. An overall inhibitory effect of tumour necrosis factor alpha (TNFα) signal was observed in all cell types; however, EPCs showed the strongest anti-inflammatory behaviour. AFCs and EPCs shared the ability to limit the activation of the signalling mediated by specific chemokines. AFCs showed a slightly senescent attitude, with a downregulation of genes related to DNA repair or pro-mitosis. Results allowed for the identification of specific molecular targets in IVD and EP cells that respond to an inflammatory environment. Such targets can be either silenced (when pathological targets) or stimulated to counteract