Mutation inε-Sarcoglycan Induces a Myoclonus-Dystonia Syndrome-Like Movement Disorder in Mice

Myoclonus dystonia syndrome(MDS)is an inherited movement disorder,and most MDS-related mutations have so far been found in theε-sarcoglycan(SGCE)coding gene.By generating SGCE-knockout(KO)and human 237 C>T mutation knock-in(KI)mice,we showed here that both KO and KI mice exerted typical movement defects similar to those of MDS patients.SGCE promoted filopodia development in vitro and inhibited excitatory synapse formation both in vivo and in vitro.Loss of function of SGCE leading to excessive excitatory synapses that may ultimately contribute to MDS pathology.Indeed,using a zebrafish MDS model,we found that among 1700 screened chemical compounds,Vigabatrin was the most potent in readily reversing MDS symptoms of mouse disease models.Our study strengthens the notion that mutations of SGCE lead to MDS and most likely,SGCE functions to brake synaptogenesis in the CNS.     

Activation of dopaminergic VTA inputs to the mPFC ameliorates chronic stress-induced breast tumor progression

AimsChronic stress plays an important role in promoting the progression and migration of cancers. However, little is known of any direct impact on tumor progression related to the regulation of emotion‐related circuitry. The aim of this study was to explore the neural‐circuit mechanisms underlying stress‐induced progression of cancers and the impact of emotion‐related regulation of circuitry on tumor growth.MethodsOptogenetic manipulation was applied to unpredictable chronic mild stress (UCMS)–treated mice bearing breast tumor cell. The stress‐related hormones, tumor‐related cytokines, the tyrosine hydroxylase (TH)–positive neurons and their fibers, dopamine receptor–positive cells, and anxiety level were measured using ELISA, immunohistochemical staining, fluorescence in situ hybridization, and behavioral test, respectively.ResultsBy investigating breast cancer mouse models with a chronic mild stress model, optogenetic stimulation, and behavioral analysis, we show that chronic stress induced anxiety‐like behavior in mice and increased serum concentration of norepinephrine and corticosterone, hormones closely related to stress and anxiety. Optogenetic activation of VTA TH terminals in the mPFC rescued anxiety‐like behavior induced by chronic stress. Chronic stress resulted in marked progression of breast tumors, and repetitive optogenetic activation of VTA TH terminals in the mPFC significantly attenuated stress‐induced progression of breast cancers and reduced serum concentration of norepinephrine and corticosterone. Furthermore, there was a positive correlation between serum norepinephrine or corticosterone concentration and tumor size.ConclusionsThese findings indicate a positive role of an emotion regulation circuit on the progression of breast cancer and reveal a link between stress, emotion regulation, and the progression of breast cancers. Our findings provide new insights pertinent to therapeutic interventions in the treatment of breast cancers.     

流动剪应力对丹酚酸B抑制血小板聚集的影响

目的研究流动剪应力对丹酚酸B抑制血小板聚集的影响及其可能的机制。方法采用生物力药理学的研究方法,2×4析因设计分组,利用BioFlux 1000控剪应力微流培养系统,分别施以0.02、1.5 Pa剪应力并联合4个剂量的丹酚酸B对血管内皮细胞(HUVECs)进行预处理20 h,收集上清液,采用联酶免疫吸附法(ELISA)检测细胞上清液中6-keto-PGF1α和vWF含量;检测上清液对ADP诱导的血小板聚集的影响;免疫荧光法分析流动内皮细胞胞浆vWF含量。结果与低剪应力流动条件相比,1.5 Pa剪应力联合100μg/mL丹酚酸B能显著提高内皮细胞分泌6-keto-PGF1α的量(P<0.05);细胞上清液明显抑制了血小板聚集(P<0.05)。剪应力的变化显著影响血管内皮细胞释放vWF(P<0.01),而丹酚酸B对血管内皮细胞释放vWF无明显影响。结论丹酚酸B可能通过促进血管内皮细胞分泌PGI2发挥抗血小板聚集的效应。从血流/血管/血液相互作用的角度看,正常的流动剪应力是丹酚酸B发挥抗血小板聚集效应的有利条件之一。     

Anterior thalamic stimulation improves working memory precision judgments

BackgroundThe anterior nucleus of thalamus (ANT) has been suggested as an extended hippocampal system. The circuit of ANT and hippocampus has been widely demonstrated to be associated with memory function. Both lesions to each region and disrupting inter-regional information flow can induce working memory impairment. However, the role of this circuit in working memory precision remains unknown.ObjectiveTo test the role of the hippocampal-anterior thalamic pathway in working memory precision, we delivered intracranially electrical stimulation to the ANT. We hypothesize that ANT stimulation can improve working memory precision.MethodsPresurgical epilepsy patients with depth electrodes in ANT and hippocampus were recruited to perform a color-recall working memory task. Participants were instructed to point out the color they were supposed to recall by clicking a point on the color wheel, while the intracranial EEG data were synchronously recorded. For randomly selected half trials, a bipolar electrical stimulation was delivered to the ANT electrodes.ResultsWe found that compared to non-stimulation trials, working memory precision judgements were significantly improved for stimulation trials. ANT electrical stimulation significantly increased spectral power of gamma (30–100 Hz) oscillations and decreased interictal epileptiform discharges (IED) in the hippocampus. Moreover, the increased gamma power during the pre-stimulus and retrieval period predicted the improvement of working memory precision judgements.ConclusionANT electrical stimulation can improve working memory precision judgements and modulate hippocampal gamma activity, providing direct evidence on the role of the human hippocampal-anterior thalamic axis in working memory precision.     

Safety evaluation of a new setup for transcranial electric stimulation during magnetic resonance imaging

BackgroundTranscranial electric stimulation during MR imaging can introduce safety issues due to coupling of the RF field with the stimulation electrodes and leads.ObjectiveTo optimize the stimulation setup for MR current density imaging (MRCDI) and increase maximum stimulation current, a new low-conductivity (σ = 29.4 S/m) lead wire is designed and tested.MethodThe antenna effect was simulated to investigate the effect of lead conductivity. Subsequently, specific absorption rate (SAR) simulations for realistic lead configurations with low-conductivity leads and two electrode types were performed at 128 MHz and 298 MHz being the Larmor frequencies of protons at 3T and 7T. Temperature measurements were performed during MRI using high power deposition sequences to ensure that the electrodes comply with MRI temperature regulations.ResultsThe antenna effect was found for copper leads at ¼ RF wavelength and could be reliably eliminated using low-conductivity leads. Realistic lead configurations increased the head SAR and the local head SAR at the electrodes only minimally. The highest temperatures were measured on the rings of center-surround electrodes, while circular electrodes showed little heating. No temperature increase above the safety limit of 39 °C was observed.ConclusionCoupling to the RF field can be reliably prevented by low-conductivity leads, enabling cable paths optimal for MRCDI. Compared to commercial copper leads with safety resistors, the low-conductivity leads had lower total impedance, enabling the application of higher currents without changing stimulator design. Attention must be paid to electrode pads.     

癫痫治疗效果的复杂度评估分析

目的:针对当前临床对癫痫患者的治疗效果还缺少一种快速、客观的评估方法,本文提出了一种使用复杂度算法快速评估癫痫患者治疗效果的分析方法。方法:通过对同一癫痫患者脑电信号治疗前后的多次采样,使用复杂度算法分析癫痫患者在尺度为120,步长为10,噪声容限为0.15时的脑电波信号,通过对比癫痫患者治疗前、后的脑电信号复杂度,从而达到评估癫痫患者治疗效果的目的。结果:癫痫患者在经过一段时间治疗后的脑电信号复杂度明显大于癫痫患者治疗前的脑电信号复杂度,并且在治疗过程中我们可以明显的看到癫痫患者脑电波的复杂度变化。结论:通过临床实践验证,复杂度算法在分析癫痫患者脑电波信号方面具有较好的一致性,可以通过分析患者的脑电信号复杂度快速的给医生一个直观的评估参考标准,且只需较短的的数据就可以达到分析目的,可能成为评估癫痫患者治疗效果的一个有效手段。     

Racial disparity in orbital morphology and spatial relations in unoperated Crouzon patients

The altered orbital morphology of patients with Crouzon syndrome could have an impact on the planning of treatment in diverse populations, in spite of the confounding influences of different cranial suture synostosis. This study attempted to explore the differences in orbital characteristics between Asian, Caucasian patients with Crouzon syndrome, associated pansynostosis. Eighty-six preoperative computed tomograms (CT) were included (Asian Crouzon syndrome: n=10; Asian controls: n=24; Caucasian Crouzon syndrome: n=19; Caucasian controls: n=33) and measured using Mimics software (Materialise). Unique cephalometric measurements related to orbital morphology and position were designed. Crouzon syndrome and race both have interactive effects on protrusion of the globe (p=0.009) and medial horizontal angle (p=0.012) in the assessment of orbital morphology. They also interact in the width of the ethmoid sinus (p=0.009) and influence bilateral orbital relations. The anteroposterior orbital roof in Caucasian patients with Crouzon syndrome was shortened by 4.09 mm (p=0.002) compared with Caucasian controls. However, in Asian patients this dimension developed normally. The anteroposterior orbital floor was significantly reduced to a similar extent in both Asian and Caucasian Crouzon patients (both p<0.001). The visual axes in Caucasian patients with Crouzon showed more inferior rotation, by 4.38° (p=0.031) than they did in Caucasian controls, but did not achieve a statistically significant difference in other comparisons. The effect of Crouzon syndrome on orbital malformation and placement is influenced by race, especially structures related to the ethmoid sinus. Asian patients need greater infraorbital advancement for better correction of orbital proptosis and aesthetic benefits, but may require less fronto-orbital advancement than Caucasian patients.     

Timing of dental extractions in patients undergoing radiotherapy and the incidence of osteoradionecrosis: a systematic review and meta-analysis

This systematic review aimed to examine whether the incidence of osteonecrosis differed between patients who have dental extractions before or after radiotherapy (RT). The reported incidence of osteoradionecrosis (ORN) of the jaws following RT to the head and neck varies widely in the literature. Currently, for patients with head and neck cancer there are no universally accepted guidelines on the optimal timing of dental surgery relative to RT to minimise incident ORN. A literature review was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) criteria. A search of PubMed, EMBASE, Evidence-Based Medicine, and Web of Science databases targeted literature published up to and including 10 April 2020. Two independent reviewers assessed studies for eligibility against inclusion criteria. An assessment of bias was conducted for each of the included studies and relevant data extracted. A meta-analysis was undertaken using the statistical methods described. Twenty-four of 708 studies were included. They were heterogeneous and included a wide variation of RT methods, head and neck malignancies, and comorbidities. While some concluded that the incidence of ORN was dependent on the timing of dental extractions in relation to RT, with regard to the risk of its development, others reported additional factors such as age, comorbidities, extent of surgical resection, and dose and field of radiation, as more important predictors than timing. In many there was consistent lack of detail around the timing of dental procedures in relation to the delivery of RT. From 21 studies including 36,294 patients, of whom 14,389 had extractions before RT, the pooled incidence of ORN was 5.5% (95% CI: 2.1% to 10.1%). Significant heterogeneity was found in Cochran’s Q-test (p < 0.001) and Higgins I² = 98.0%. From 21 studies including 37,805 patients, of whom 6030 had extractions after RT, the pooled incidence of ORN was 5.3% (95% CI: 2.9% to 8.2%). Significant heterogeneity was found in Cochran’s Q-test (p < 0.001) and Higgins I² = 80.0%. There was no statistically significant difference between these two groups (random-effects model Q=0.12, p=0.73). Large, longitudinal studies with a priori-specified methods are needed to identify, recruit, and prospectively follow patients with head and neck cancer for the onset of ORN after dental surgery. This will allow clinical guidelines to be established to assist clinicians to plan treatment when extractions are indicated in patients undergoing RT to the head and neck.