Tumor-induced erythroid precursor-differentiated myeloid cells mediate immunosuppression and curtail anti-PD-1/PD-L1 treatment efficacy

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Lateral ventricular liponeurocytoma: Review of literature and case illustration

BackgroundLiponeurocytoma is an uncommon tumor of the central nervous system. It is very rare for this tumor to originate within the lateral ventricle. In the context of the rarity of this tumor entity, this review article aims to summarize the clinical, radiological, and pathological features of lateral ventricular liponeurocytoma to facilitate its diagnosis and management.MethodsHere, we conduct a systematic literature review using the Pubmed, Scopus, and Cochrane Library database for all cases of lateral ventricular liponeurocytoma. A case illustration complements this review.ResultsThe described cases from 1997 onward include 14 cases that have been published in full papers in the English literature. Six additional cases are reported in short English abstracts in full non-English papers, and one case was described in a central neurocytoma report. There is a definite male predominance of 70% (14 male) and a mean age of 37 years (range 24–62). Heterogenous enhancement and signals in magnetic resonant images (MRI) are the radiological characteristics. In all reported cases, the presence of lipocytes and fat vacuoles is considered the paramount histopathological feature. Total surgical resection was achieved in 80% (12 out of 15) of the cases. Only two cases (including ours) received radiation therapy. Recurrence was seen in two patients during follow-up that was treated by radiation therapy in one and surgery in the other. The proliferation index is mostly below 5% in all cases, with the Ki-67 range between < 1% to 10%.ConclusionsLateral ventricular liponeurocytoma has been treated effectively by surgical resection in a limited number of cases. The decision for radiation therapy is based on a high proliferation index and tumor recurrence.     

Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome

PurposeA role for the immune system in causing myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is long suspected, but few studies have looked for specific autoantibodies that might contribute to the symptoms. Our aim was to look for evidence of antibodies to neuronal proteins in patients with ME/CSF.MethodsSera samples from 50 patients and 50 healthy individuals were sent coded to the Neuroimmunology Laboratory in Oxford. Screening for antibody binding to neuronal tissue was performed on brain tissue and neuronal cultures. Specific serum antibodies were assessed by antigen-specific cell-based assays and radioimmunoassays. After antibody testing, the associations between seropositive status and clinical data were investigated.FindingsOverall, 8 patients and 11 participants were found to have some serum immunoreactivity toward neuronal or neuromuscular junction proteins, but only 1 patient and 2 participants had specific serum antibodies. Nevertheless, seropositive status in patients with ME was associated with shorter duration since onset and a more severe disease.ImplicationsThe results indicate no overall increased frequency of antibodies to neuronal proteins in ME/CSF and no evidence of a specific antibody that might be causative or contribute to clinical features in patients. However, the association of seropositive status with shorter duration of disease and more severe symptoms suggests a possible role of antibodies at onset in some patients and should be the focus of future studies.     

基于神经血管单元各组成部分保护作用的中药抗缺血性脑卒中的研究进展

脑卒中是一种具有极高致死率的脑血管疾病，严重影响着人们的健康和生活。随着神经血管单元概念的提出，脑卒中的治疗从单一的神经元保护转变为对神经血管单元各组成部分的保护。中药具有多成分、多途径、多靶点等特点，在脑卒中治疗中受到广泛关注。中医认为，脑卒中的发病因素与“风”“痰”“瘀”“火”“气”“虚”密切相关，其中“虚”“瘀”“痰”贯穿脑卒中发生发展的始终。研究表明，从“虚”“瘀”“痰”论治的中药在脑卒中治疗中发挥着重要作用。综述了中药对缺血性卒中后神经血管单元各组成部分的保护作用。     

Disruption of Conscious Access in Psychosis Is Associated with Altered Structural Brain Connectivity

According to global neuronal workspace (GNW) theory, conscious access relies on long-distance cerebral connectivity to allow a global neuronal ignition coding for conscious content. In patients with schizophrenia and bipolar disorder, both alterations in cerebral connectivity and an increased threshold for conscious perception have been reported. The implications of abnormal structural connectivity for disrupted conscious access and the relationship between these two deficits and psychopathology remain unclear. The aim of this study was to determine the extent to which structural connectivity is correlated with consciousness threshold, particularly in psychosis. We used a visual masking paradigm to measure consciousness threshold, and diffusion MRI tractography to assess structural connectivity in 97 humans of either sex with varying degrees of psychosis: healthy control subjects (n = 46), schizophrenia patients (n = 25), and bipolar disorder patients with (n = 17) and without (n = 9) a history of psychosis. Patients with psychosis (schizophrenia and bipolar disorder with psychotic features) had an elevated masking threshold compared with control subjects and bipolar disorder patients without psychotic features. Masking threshold correlated negatively with the mean general fractional anisotropy of white matter tracts exclusively within the GNW network (inferior frontal-occipital fasciculus, cingulum, and corpus callosum). Mediation analysis demonstrated that alterations in long-distance connectivity were associated with an increased masking threshold, which in turn was linked to psychotic symptoms. Our findings support the hypothesis that long-distance structural connectivity within the GNW plays a crucial role in conscious access, and that conscious access may mediate the association between impaired structural connectivity and psychosis.     

癫痫持续状态后小鼠海马组织神经元中微管蛋白和内体-溶酶体系统表达的变化及其意义

目的：探讨癫痫持续状态（SE）后小鼠海马组织神经元中微管蛋白β-tubulin和内体-溶酶体系统表达的变化，阐明神经元迟发性死亡过程中微管和内体-溶酶体系统的变化规律。方法：40只雄性ICR小鼠分为对照组（n=7，给予生理盐水）和实验组（n=33，给予匹鲁卡品），实验组中达到SE标准的SE小鼠根据SE后时间分为SE1d、SE2d、SE3d和SE7d组（n=5）。Nissl和Fluoro-Jade B （F-JB）染色检测各组小鼠海马组织神经元损伤情况，免疫荧光法检测各组小鼠海马组织神经元中微管蛋白β-tubulin、内体蛋白Rab5和溶酶体结构蛋白LAMP1表达强度及β-tubulin、Rab5和LAMP1阳性面积百分比；双重荧光法检测各组小鼠海马组织CA1区β-tubulin与Rab5和LAMP1表达的关系。结果：与对照组比较，SE1d组小鼠海马CA1和CA3区神经元数减少（P<0.01），F-JB阳性细胞数增加（P<0.01）；SE2d、SE3d和SE7d组小鼠海马组织中Nissl阳性神经元数明显减少（P<0.01）。与对照组比较，SE2d、SE3d和SE7d组小鼠海马组织中F-JB阳性神经元数增加（P<0.01）。与对照组比较，SE2d、SE3d和SE7d组小鼠海马CA1和CA3区神经元树突中β-tubulin阳性面积百分比明显降低（P<0.05），其变化趋势与神经元损伤相似。与对照组比较，SE1d、SE 2d、SE 3d和SE 7d组小鼠海马组织神经元中Rab5和LAMP1表达强度随着时间延长呈下降趋势；Rab5阳性面积百分比明显降低（P<0.05或P<0.01）；LAMP1阳性面积百分比在SE后第1天出现一过性增多，之后逐渐减少（P<0.05或P<0.01）。双重荧光染色检测，SE后1 d是早期内体减少和溶酶体一过性增多的关键点，并与神经元微管损伤的出现时间极为一致。结论：SE引起神经元迟发性死亡的同时神经元微管骨架受损，内体-溶酶体系统的定位和功能也发生异常改变。     

Brain oscillatory activity as a biomarker of motor recovery in chronic stroke

In the present work, we investigated the relationship of oscillatory sensorimotor brain activity to motor recovery. The neurophysiological data of 30 chronic stroke patients with severe upper‐limb paralysis are the basis of the observational study presented here. These patients underwent an intervention including movement training based on combined brain–machine interfaces and physiotherapy of several weeks recorded in a double‐blinded randomized clinical trial. We analyzed the alpha oscillations over the motor cortex of 22 of these patients employing multilevel linear predictive modeling. We identified a significant correlation between the evolution of the alpha desynchronization during rehabilitative intervention and clinical improvement. Moreover, we observed that the initial alpha desynchronization conditions its modulation during intervention: Patients showing a strong alpha desynchronization at the beginning of the training improved if they increased their alpha desynchronization. Patients showing a small alpha desynchronization at initial training stages improved if they decreased it further on both hemispheres. In all patients, a progressive shift of desynchronization toward the ipsilesional hemisphere correlates significantly with clinical improvement regardless of lesion location. The results indicate that initial alpha desynchronization might be key for stratification of patients undergoing BMI interventions and that its interhemispheric balance plays an important role in motor recovery.     

Patient Management Assisted by a Neural Network Reduces Mortality in an Intermediate Care Unit

IntroductionMortality risk prediction for Intermediate Respiratory Care Unit's (IRCU) patients can facilitate optimal treatment in high-risk patients. While Intensive Care Units (ICUs) have a long term experience in using algorithms for this purpose, due to the special features of the IRCUs, the same strategics are not applicable. The aim of this study is to develop an IRCU specific mortality predictor tool using machine learning methods.MethodsVital signs of patients were recorded from 1966 patients admitted from 2007 to 2017 in the Jiménez Díaz Foundation University Hospital's IRCU. A neural network was used to select the variables that better predict mortality status. Multivariate logistic regression provided us cut-off points that best discriminated the mortality status for each of the parameters. A new guideline for risk assessment was applied and mortality was recorded during one year.ResultsOur algorithm shows that thrombocytopenia, metabolic acidosis, anemia, tachypnea, age, sodium levels, hypoxemia, leukocytopenia and hyperkalemia are the most relevant parameters associated with mortality. First year with this decision scene showed a decrease in failure rate of a 50%.ConclusionsWe have generated a neural network model capable of identifying and classifying mortality predictors in the IRCU of a general hospital. Combined with multivariate regression analysis, it has provided us with an useful tool for the real-time monitoring of patients to detect specific mortality risks. The overall algorithm can be scaled to any type of unit offering personalized results and will increase accuracy over time when more patients are included to the cohorts.