Studies have implicated astrocytic dysfunction in Alzheimer's disease (AD). However, the role of astrocytes in the pathophysiology and treatment of the disease is poorly characterized. Here, we identified astrocytes as independent key factors involved in several Alzheimer-like phenotypes in an APP/PS1 mouse model, including amyloid pathology, altered neuronal and synaptic properties, and impaired cognition. In vitro astrocytes from APP/PS1 mice induced synaptotoxicity as well as reduced dendritic complexity and axonal branching of hippocampal neurons. These astrocytes produced high levels of soluble β-amyloid (Aβ) which could be significantly inhibited by fluoxetine (FLX) via activating serotonin 5-HT2 receptors. FLX could also protect hippocampal neurons against astrocyte-induced neuronal damage in vitro. In the same APP/PS1 mice, FLX inhibited activation of astrocytes, lowered Aβ products, ameliorated neurotoxicity, and improved behavioral performance. These findings may provide a basis for the clinical application of FLX in patients, and may also lay the groundwork for exploration of other novel astrocyte-based therapies of AD.
The results of the present study suggest that there may be limited clinical use for determining AR expression (if evaluated in hot spots) in men with localized PCa.
Introduction
Deep brain stimulation (DBS) is an effective treatment for patients with Parkinson’s disease (PD). On time follow-up and timely programing of symptoms are important measures to maintain the effectiveness of DBS. Due to the highly contagious nature of 2019-nCoV, patients were quarantined. With the help of Internet technologies, we continued to provide motor and non-motor symptom assessment and remote programming services for postsurgical PD-DBS patients during this extraordinary period.
Methods
A retrospective analysis was performed on postsurgical PD-DBS patients who could not come to our hospital for programming due to the impact of the 2019-nCoV. The differences between the pre- and post-programming groups were analyzed. We designed a 5-level Likert rating scale to evaluate the effects and convenience of the remote programming and Internet self-evaluation procedures.
Results
Of the 36 patients engaged in the remote programming, 32 patients met the inclusion criteria. Four of the 32 patients set initiated stimulation parameters, and the other 28 patients had significant improvement in UPDRS-III. Nearly all the 28 patients were satisfied with the effect of the remote programming. Most of the patients were willing to use remote programming again.
Conclusion
Remote programming based on the online evaluation of patient’s symptoms can help improve motor symptoms of postsurgical DBS patients with PD during the quarantine period caused by 2019-nCoV.
Electronic supplementary material
The online version of this article (10.1007/s00415-020-10273-z) contains supplementary material, which is available to authorized users.
Holmium laser enucleation of the prostate is a safe and effective treatment option for benign prostatic hyperplasia, even when performed by inexperienced surgeons. The incidence of complications decreases with increasing experience with the procedure.
Retroperitoneal laparoscopic liposuction with suction units is safe and effective for resection of relatively large adrenal myelolipomas. Deflation and shrinkage of the tumor make the operation safer and easier without affecting its pathological diagnosis.
Prostate cancer is a common malignant tumor in elderly men. As a novel metabolic-reprogramming molecule, the role of ankyrin repeat domain 22 (ANKRD22) in the tumorigenesis and progression of prostate cancer remains unknown. In the present study, mouse monoclonal antibodies against human ANKRD22 were prepared using recombinant ANKRD22 from prokaryotic expression and validated. Subsequently, these antibodies were used to evaluate ANKRD22 levels via immunohistochemical staining in prostate cancer tissues. Finally, the association between ANKRD22 levels and prostate cancer progression was analyzed in 636 samples of prostate cancer using The Cancer Genome Atlas (TCGA) database. A total of four anti-ANKRD22 monoclonal antibodies were generated and validated, which could be effectively blocked by recombinant ANKRD22 protein. Using these antibodies for immunohistochemical staining, ANKRD22 was detected in prostate cancer cells in both the cytoplasm and nucleus. Bioinformatics analysis demonstrated that the mRNA level of ANKRD22 was inversely associated with prostate cancer stage (P<0.05) and Gleason score (P<0.01) in TCGA database. Patients with higher ANKRD22 mRNA levels exhibited longer disease-free survival following radical prostatectomy. These findings suggest that ANKRD22 may negatively regulate the progression of prostate cancer. The prepared ANKRD22 antibodies with high specificity provide a powerful tool in ANKRD22 research.
Objectives. To analyze the hyperhidrosis neural network structure induced by subthalamic nucleus (STN) - deep brain stimulation (DBS). Materials and Methods. Patients with Parkinson’s disease treated with STN-DBS in Changhai Hospital between July 1, 2015, and December 1, 2016, were analyzed retrospectively. Using records of side effects of the intraoperative macrostimulation test, patients with skin sweats were selected as the sweating group. Based on the number of cases in the sweating group, the same number of patients was randomly selected from other STN-DBS patients without sweating to form the control group. The study standardized electrode position with Lead-DBS software to Montreal Neurological Institute (MNI) standard stereotactic space to compare the differences in three-dimensional coordinates of activated contacts between groups. Results. Of 355 patients, 11 patients had sweats during intraoperative macrostimulation tests. There was no significant difference in the preoperative baseline information and the postoperative UPDRS-III improvement rate (Med-off, IPG-on) between groups. Contacts inducing sweat were more medial (X-axis) (11.02 ± 0.69 mm vs 11.98 ± 0.84 mm, P=0.00057) and more upward (Z-axis) (−7.15 ± 1.06 mm VS −7.98 ± 1.21 mm, P=0.032) than those of the control group. The straight-line distance between the center of the sweat contact and the nearest voxel of the red nucleus was closer than that of the control group (2.72 ± 0.65 mm VS 3.76 ± 0.85 mm, P=0.00012). Conclusions. STN-DBS-induced sweat indicated that the contact was at superior medial of STN.
Objective This study aimed to analyze the risk factors of intracranial hemorrhage (ICH) after deep brain stimulation (DBS) for idiopathic Parkinson’s disease (PD). Methods Patients who received DBS from March 2014 to December 2016 were retrospectively analyzed. The hemorrhage index was derived by combining the hemorrhagic volume and clinical manifestations of ICH. All patients with IHC were followed up for 2 years. Results Computed tomography showed 13 events of ICH in 11 patients (nine cases in the subthalamic nucleus), including eight cases with symptomatic hemorrhage (seven cases in the subthalamic nucleus). Hemorrhage was characterized by intracranial hematoma in the electrode puncture tract. Male sex and hypertension were significant risk factors for ICH. Hemorrhage in the preferred puncture side was significantly higher than that in the non-preferred puncture side. The mean hemorrhage index was 2.23 ± 0.83 in 11 patients, and no permanent neurological impairment was found during the 2-year follow-up. The effect of DBS on motor symptoms was similar in patients with and without ICH. Conclusion Male sex and hypertension are risk factors of ICH after DBS in PD. The risk of hemorrhage on the first puncture site is significantly higher than that on the second puncture site.
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