关键词： chronic immobilization stress   Cydonia oblonga   depression   hippocampal neurogenesis  

摘要： It is known that chronic stress is a contributing factor to several physical and mental diseases. In this study, we examined the effect of hydroethanolic extract of Cydonia oblonga fruit (HECO, 300 mg/kg) in chronically immobilized rats on physiological and behavioral parameters by the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST) and on neurological alterations by analysis of the hippocampal neurogenesis. A daily 6 hr exposure to chronic immobilization stress (CIS) for 21 consecutive days induced anxiety- and depressive-like behaviors in rats' concomitant with decreased weight gain and increased plasma corticosterone (CORT) levels, rats also showed atrophy in the CA3 subregion of the hippocampus and a decreased number of Ki67 and DCX positive cells in the dentate gyrus (DG). Treatment with HECO successfully suppressed the physiological and behavioral markers of the CIS and prevents the structural abnormality and the impaired cell proliferation in the hippocampus. Moreover, the daily administration of HECO improved the mood function in normal rats. Taking together, our findings demonstrate, for the first time, the anti-depressive effect of C. oblonga fruit by enhancing the hippocampal neurogenesis in the rat model of depression.

关键词： Functional neurological symptom disorder   Conversion disorder   Medical education   Neuroscience   Neuropsychiatry  

摘要： Objectives Psychiatry training is lacking examples of neuroscience education that translates neuroscience literature into accessible clinically oriented concepts. The authors created a teaching activity using patient-centered neuroscience education that focused on delivering the diagnosis of functional neurological disorder (FND). This study aimed to (i) develop a workshop modeling a clinician-patient interaction, (ii) provide a modern neuroscience perspective of FND, and (iii) evaluate the change in clinicians' perceptions of FND. Methods A total of six workshops (each 1 h long and consisting of a video, PowerPoint slides, and pre and post questionnaires) were conducted. Pairedttests were used to measure the change. Results Forty-seven clinicians participated. After completing the workshop, nearly all endorsed that functional symptoms are "real" (95%) and that treatment is helpful (100%). Participants also reported a greater comfort level with discussing FND diagnosis (46% vs 85%,p< 0.001), an overall increase in understanding the disorder (33% vs 82%,p< 0.001), assessing need for tests (33% vs 66%,p< 0.001), understanding treatment options (26% vs 89%,p< 0.001), and recognition that treatment can help control these symptoms (81% vs 100%,p< 0.01). In addition, learners were more likely to report that patients with FND are truthful (75% vs 95%,p< 0.001) and less likely to be manipulative (48% vs 80%,p< 0.001). Conclusions A brief, educational intervention using neuroscience-based content was found to significantly improve clinicians' perception and confidence when delivering the diagnosis of FND.

关键词： childhood hematology   chemotherapy   neurotoxicity   leukoencephalopathy   risk classification  

摘要： Simple Summary In this study, we investigated standardized post-chemotherapy magnetic resonance (MR) scans for leukoencephalopathy and patient- and treatment-related risk factors in childhood leukemia patients. As prevalence numbers are limited, our study provides the required estimations for this population. Furthermore, we demonstrate that younger patients might be more at-risk for development of leukoencephalopathy (LE), and that a higher intravenous methotrexate (IV-MTX) dose has a cumulative toxic effect, while the number of intrathecal administrations was not significantly associated with the extent of LE. This can suggest we should modify chemotherapeutic treatment regimens by decreasing the number of IV-MTX applications, with special attention for younger patients. Methotrexate (MTX) is associated with leukoencephalopathy (LE) in children treated for lymphoblastic leukemia/lymphoma (ALL/LBL). However, large-scale studies with systematic MR acquisition and quantitative volumetric lesion information remain limited. Hence, the prevalence of lesion burdens and the potential risk factors of LE in this population are still inconclusive. FLAIR-MRI scans were acquired at the end of treatment in children who were treated for ALL/LBL, which were quantitatively analyzed for LE. Voxels were assigned to the lesion segmentation if indicated by two raters. Logistic and linear regression models were used to test whether lesion presence and size were predicted by risk factors such as age at diagnosis, gender, intrathecal (IT-) or intravenous (IV-)MTX dose, CNS invasion, and acute neurological events. Patients with a pre-existing neurological condition or low-quality MR scan were excluded from the analyses. Of the 129 patients, ten (8%) suffered from CNS invasion. Chemotherapy-associated neurological events were observed in 13 patients (10%) during therapy, and 68 patients (53%) showed LE post-treatment. LE was more frequent in cases of lower age and higher cumulative IV-MTX

关键词： Depatuxizumab mafodotin   Glioblastoma   Lomustine   Patient-reported outcomes   Phase II   Quality of life   Randomised   Temozolomide   Visual disorders  

摘要： Background: In the EORTC 1410/ INTELLANCE 2 randomised, phase II study (NCT02343406), with the antibody-edrug conjugate depatuxizumab mafodotin (Depatux-M, ABT-414) in patients with recurrent EGFR-amplified glioblastoma, the primary end-point (overall survival) was not met, and the drug had ocular dose-limiting toxicity. This study reports results from the prespecified health-related quality of life (HRQoL) and neurological deterioration-free survival (NDFS) exploratory analysis. Patients and methods: Patients (n Z 260) were randomised 1:1:1 to receive either Depatux-M 1.25 mg/kg or 1.0 mg/kg intravenously every 2 weeks with oral temozolomide (TMZ) 150 mg/ m(2), Depatux-M alone, or TMZ or oral lomustine (CCNU) 110 mg/ m(2) ( TMZ/CCNU). HRQoL outcomes were recorded using the EORTC core Quality of Life QLQ-C30, and brain cancer-specific QLQ-BN20 questionnaires. Questionnaires were completed at baseline, weeks 8 and 16, and month 6, and changes from baseline to each time point were calculated. NDFS was defined as time to first deterioration in World Health Organisation performance status. Results: Compliance with HRQoL was 88.1% at baseline and decreased to 37.9% at month 6. Differences from baseline between Depatux-M arms and TMZ/CCNU in global health/QoL status throughout treatment did not reach clinical relevance (>= 10 points). Self-reported visual disorders deteriorated to a clinically relevant extent with Depatux-M arms versus TMZ/CCNU at all timepoints (mean differences range: 24.6-35.1 points). Changes from baseline for other HRQoL scales and NDFS were generally similar between treatment arms. Conclusions: Depatux-M had no impact on HRQoL and NDFS in patients with EGFRamplified recurrent glioblastoma, except for more visual disorders, an expected side- effect of the study drug. (C) 2021 Elsevier Ltd. All rights reserved.

关键词： Blind   Functional magnetic resonance imaging   Motor imagery   Supplementary motor area   Cerebellum  

摘要： In people with normal sight, mental simulation (motor imagery) of an experienced action involves a multisensory (especially kinesthetic and visual) emulation process associated with the action. Here, we examined how long-term blindness influences sensory experience during motor imagery and its neuronal correlates by comparing data obtained from blind and sighted people. We scanned brain activity with functional magnetic resonance imaging (fMRI) while 16 sighted and 14 blind male volunteers imagined either walking or jogging around a circle of 2 m radius. In the training before fMRI, they performed these actions with their eyes closed. During scanning, we explicitly instructed the blindfolded participants to generate kinesthetic motor imagery. After the experimental run, they rated the degree to which their motor imagery became kinesthetic or spatio-visual. The imagery of blind people was more kinesthetic as per instructions, while that of the sighted group became more spatio-visual. The imagery of both groups commonly activated bilateral frontoparietal cortices including supplementary motor areas (SMA). Despite the lack of group differences in degree of brain activation, we observed stronger functional connectivity between the SMA and cerebellum in the blind group compared to that in the sighted group. To conclude, long-term blindness likely changes sensory emulation during motor imagery to a more kinesthetic mode, which may be associated with stronger functional coupling in kinesthetic brain networks compared with that in sighted people. This study adds valuable knowledge on motor cognition and mental imagery processes in the blind.

关键词： Therapeutic hypothermia   Targeted temperature management   Cardiac arrest   Pre-hospital   Outcome  

摘要： Objective: Survival after pre-hospital cardiac arrest (PHCA) remains low. Pre-hospital therapeutic hypothermia (PTH) is believed to improve patient's outcomes, but data on efficacy and safety remains scarce. Herein, we aimed to assess the influence of PTH on survival, neurological outcome, and adverse effects in patients with PHCA. Materials and methods: A literature search of PubMed CENTRAL, EMBASE, and The Cochrane Central Register of Controlled Trials databases from inception to August 2019 was conducted and retrieved abstracts were independently assessed by two reviewers. The primary outcome was survival to hospital discharge with a favorable neurological outcome. Secondary outcomes were survival to hospital discharge and temperature upon hospital *** safety outcomes included pulmonary edema and recurrent arrest during transport to the hospital. We also considered a favorable neurological function to hospital discharge or longest post arrest follow-up. Results: Eleven studies including 4891 patients were included into final analysis. The survival to hospital discharge did not differ between PTH and control group (RR 1.02;95%Cl 0.93 to 1.12). Among 4891 participants (2466 in PTH group and 2425 in control group), 1087 participants (564 vs. 523, respectively) had a favorable neurological outcome. Pulmonary edema occurred in 320 cases in PTH group and 273 in control group with significant heterogeneity (RR 0.90, 95%CI 0.59-138;12 = 80%). The pooled results showed a significant difference in rearrests between the PTH and control group (RR 1.19;95%CI 1.00 to 1.42). Conclusion: Our analysis demonstrates that PTH does not improve survival at discharge or neurological outcome. (C) 2020 Elsevier Inc. All rights reserved.

摘要： Purpose This study aimed to identify the genetic cause of a new multiple congenital anomalies syndrome observed in three individuals from two unrelated families. Methods Clinical assessment was conducted prenatally and at different postnatal stages. Genetic studies included exome sequencing (ES) combined with single-nucleotide polymorphism (SNP) array based homozygosity mapping and trio ES. Dermal fibroblasts were used for functional assays. Results A clinically recognizable syndrome characterized by severe developmental delay, variable brain anomalies, congenital heart defects, dysmorphic facial features, and a distinctive type of synpolydactyly with an additional hypoplastic digit between the fourth and fifth digits of hands and/or feet was identified. Additional features included eye abnormalities, hearing impairment, and electroencephalogram anomalies. ES detected different homozygous truncating variants in MAPKAPK5 in both families. Patient-derived cells showed no expression of MAPKAPK5 protein isoforms and reduced levels of the MAPKAPK5-interacting protein ERK3. F-actin recovery after latrunculin B treatment was found to be less efficient in patient-derived fibroblasts than in control cells, supporting a role of MAPKAPK5 in F-actin polymerization. Conclusion Our data indicate that loss-of-function variants in MAPKAPK5 result in a severe developmental disorder and reveal a major role of this gene in human brain, heart, and limb development.

关键词： COVID-19   Education   Neurosurgery   New York City   Pandemic   Redeployment  

摘要： Coronavirus disease 2019 (COVID-19) has disrupted lives and indelibly impacted the practice of medicine since emerging as a pandemic in March 2020. For neurosurgery departments throughout the United States, the pandemic has created unique challenges across subspecialties in devising methods of triage, workflow, and operating room safety. Located in New York City, at the early epicenter of the COVID-19 crisis, the Weill Cornell Medicine Department of Neurological Surgery was disrupted and challenged in many ways, requiring adaptations in clinical operations, workforce management, research, and education. Through our department's collective experience, we offer a glimpse at how our faculty and administrators overcame obstacles, and transformed in the process, at the height of the COVID-19 pandemic.