Automated classification of depression from structural brain measures across two independent community‐based cohorts

Major depressive disorder (MDD) has been the subject of many neuroimaging case–control classification studies. Although some studies report accuracies ≥80%, most have investigated relatively small samples of clinically‐ascertained, currently symptomatic cases, and did not attempt replication in larger samples. We here first aimed to replicate previously reported classification accuracies in a small, well‐phenotyped community‐based group of current MDD cases with clinical interview‐based diagnoses (from STratifying Resilience and Depression Longitudinally cohort, ‘STRADL’). We performed a set of exploratory predictive classification analyses with measures related to brain morphometry and white matter integrity. We applied three classifier types—SVM, penalised logistic regression or decision tree—either with or without optimisation, and with or without feature selection. We then determined whether similar accuracies could be replicated in a larger independent population‐based sample with self‐reported current depression (UK Biobank cohort). Additional analyses extended to lifetime MDD diagnoses—remitted MDD in STRADL, and lifetime‐experienced MDD in UK Biobank. The highest cross‐validation accuracy (75%) was achieved in the initial current MDD sample with a decision tree classifier and cortical surface area features. The most frequently selected decision tree split variables included surface areas of bilateral caudal anterior cingulate, left lingual gyrus, left superior frontal, right precentral and paracentral regions. High accuracy was not achieved in the larger samples with self‐reported current depression (53.73%), with remitted MDD (57.48%), or with lifetime‐experienced MDD (52.68–60.29%). Our results indicate that high predictive classification accuracies may not immediately translate to larger samples with broader criteria for depression, and may not be robust across different classification approaches.     

Evaluating the inhibitory potential of Withania somnifera on platelet aggregation and inflammation enzymes: An in vitro and in silico study

Context Withania somnifera (L.) Dunal is traditionally used for treating various ailments, but lacks scientific evaluation.

Objective This study evaluates Withania somnifera (WS) for its effect on platelet activity and inflammatory enzymes.

Materials and methods Aqueous and ethanolic (1:1) leaf extracts were subjected to in vitro indirect haemolytic activity using Naja naja venom, human platelet aggregation was quantified for lipid peroxidation using arachidonic acid (AA) as agonist and 5-lipoxygenase (5-LOX) levels were determined using standard spectrometric assays. Further, molecular docking was performed by the ligand fit method using molegro software package (Molegro ApS, Aarhus, Denmark).

Results The study found that aqueous and ethanol extracts have very negligible effect (15%) with an IC₅₀ value of 13.8?mg/mL on PLA₂ from Naja naja venom. Further, extracts of WS also had very little effect (18%) with an IC₅₀ value of 16.6?mg/mL on malondialdehyde (MDA) formation. However, a 65% inhibition of 5-LOX with an IC₅₀ value of 0.92?mg/mL was observed in 1:1 ethanol extracts. The same was evident from SAR model with the active ingredient withaferin A binding predominantly on Phe 77, Tyr 98, Arg 99, Asp 164, Leu 168, Ser 382, Arg 395, Tyr 396 and Tyr 614 with an atomic contact energy value of??128.96 compared to standard phenidone (?103.61). Thus, the current study validates the application of WS for inflammatory diseases.

Conclusion This study reveals the inhibitory potential of W. somnifera on inflammatory enzymes and platelet aggregation. Thus, WS can serve as a newer, safer and affordable medicine for inflammatory diseases.     

经食管实时三维超声心动图评价房性心律失常对二尖瓣结构和功能的影响

目的:应用经食管实时三维超声心动图(RT-3D-TEE)技术,探讨房性心律失常对二尖瓣结构和功能的影响.方法:选取2018年6月~2019年6月本院收治的房性心律失常拟行射频消融的患者49例纳入观察组,另外选取21例正常窦性心律者作为对照组,所有患者均行经胸超声心电图(TTE)和经食管实时三维超声心动图(RT-3D-TEE)检查,将两组患者的瓣环投影面积(A2D)、瓣环周长(C3D)、瓣环高度(H)、瓣环前后径(DAP)、瓣环前外侧至后内侧直径(DAIPm)、左室射血分数(LVEF)、左心房前后径(Lad)等参数进行比较,并分别计算对合面积和对合指数,之后采取二项Logistic回归分析或逐步线性回归对各参数及临床因素与对合指数的相关性进行分析.结果:两组患者在LVEF和对合面积方面的比较无明显差异(P>0.05),在A2D、C3D、H、DA、PDAIPm、Lad方面的比较,房性心律失常组患者明显高于正常窦性心律组患者(P<0.05),且观察组患者的对合指数明显降低(P<0.05).将49例观察组患者以不同心律失常类型分为持续性房颤、阵发性房颤、房扑、混合型房性心律失常4个亚组,采用单因素方差分析,发现在LVEF、C3D、Lad、对合指数方面的比较,各亚组间无明显差异(P>0.05).采用二项Logistic回归分析发现,女性是导致对合指数低的危险因素,另外对合指数较低、房性心律失常是导致二尖瓣返流的重要因素.结论:房性心律失常对患者二尖瓣的A2D、C3D、H、DA、PDAIPm、Lad等都会造成较大影响,从而降低对合指数,影响二尖瓣的正常功能,导致二尖瓣返流的发生.     

行为-结构化-关系干预模式对短期住院孤独症谱系障碍儿童的疗效分析

目的 探讨以行为-结构化-关系(BSR)干预模式对短期住院孤独症谱系障碍(ASD)儿童的干预疗效,为改善ASD儿童的预后提供参考依据。方法 选取2015年12月－2016年12月确诊为ASD的2~6岁儿童141例,随机分为治疗组和对照组。治疗组ASD儿童均接受BSR模式的短期课程训练,训练课程包括个别辅导、游戏课、运动课、音乐课等,每天训练时间6 h,持续1个月;对照组ASD儿童处于干预等待,接受随访观察和评估。所有ASD儿童干预前、后均接受儿童心理教育评估(第三版)(PEP-3)来进行各方面能力变化的评估。结果 治疗组、对照组干预前各副测验的原积分差异无统计学意义(P>0.05)。两组ASD儿童干预后认知、语言理解、模仿、情感表达、社会互动、行为特征-非语言、适应行为的原积分比较,差异均有统计学意义(t=2.41、2.02、4.14、3.69、4.42、2.69、2.96,P<0.05);但小肌肉、大肌肉、自理的原积分比较,差异无统计学意义(t=-1.13、-1.05、-0.84,P>0.05)。结论 BSR干预模式能够有效改善短期住院ASD儿童的预后,可推广用于儿童ASD的治疗。     

Chalcone hybrids and their antimalarial activity

Malaria, one of the most striking, re-emerging infectious diseases caused by the genus Plasmodium, places a huge burden on global healthcare systems. A major challenge in the control and eradication of malaria is the continuous emergence of increasingly widespread drug-resistant malaria, creating an urgent need to develop novel antimalarial agents. Chalcone derivatives are ubiquitous in nature and have become indispensable units in medicinal chemistry applications due to their diverse biological profiles. Many chalcone derivatives demonstrate potential in vitro and in vivo antimalarial activity, so chalcone could be a useful template for the development of novel antimalarial agents. This review covers the recent development of chalcone hybrids as antimalarial agents. The critical aspects of the design and structure–activity relationship of these compounds are also discussed.     

Ad-CD40L mobilizes CD4 T cells for the treatment of brainstem tumors

BackgroundDiffuse midline glioma, formerly DIPG (diffuse intrinsic pontine glioma), is the deadliest pediatric brainstem tumor with median survival of less than one year. Here, we investigated (i) whether direct delivery of adenovirus-expressing cluster of differentiation (CD)40 ligand (Ad-CD40L) to brainstem tumors would induce immune-mediated tumor clearance and (ii) if so, whether therapy would be associated with a manageable toxicity due to immune-mediated inflammation in the brainstem.MethodsSyngeneic gliomas in the brainstems of immunocompetent mice were treated with Ad-CD40L and survival, toxicity, and immune profiles determined. A clinically translatable vector, whose replication would be tightly restricted to tumor cells, rAd-Δ24-CD40L, was tested in human patient–derived diffuse midline gliomas and immunocompetent models.ResultsExpression of Ad-CD40L restricted to brainstem gliomas by pre-infection induced complete rejection, associated with immune cell infiltration, of which CD4+ T cells were critical for therapy. Direct intratumoral injection of Ad-CD40L into established brainstem tumors improved survival and induced some complete cures but with some acute toxicity. RNA-sequencing analysis showed that Ad-CD40L therapy induced neuroinflammatory immune responses associated with interleukin (IL)-6, IL-1β, and tumor necrosis factor α. Therefore, to generate a vector whose replication, and transgene expression, would be tightly restricted to tumor cells, we constructed rAd-Δ24-CD40L, the backbone of which has already entered clinical trials for diffuse midline gliomas. Direct intratumoral injection of rAd-Δ24-CD40L, with systemic blockade of IL-6 and IL-1β, generated significant numbers of cures with readily manageable toxicity.ConclusionsVirus-mediated delivery of CD40L has the potential to be effective in treating diffuse midline gliomas without obligatory neuroinflammation-associated toxicity.     

小檗碱通过影响糖原结构调节肝糖代谢研究

目的探讨小檗碱调节糖原代谢的机制及对糖原结构的影响。方法采用自发型糖尿病模型db/db小鼠作为疾病模型鼠,考察小檗碱对db/db小鼠血糖水平的影响;提取小鼠的肝糖原进行体积排阻色谱(SEC)和透射电镜(TEM)分析,考察小檗碱对db/db小鼠肝糖原的结构影响,并探讨其影响机制。结果小檗碱可以显著性降低db/db小鼠的空腹血糖,降低db/db小鼠血清胰岛素水平;改善db/db小鼠肝糖原的结构不稳定性;降低db/db小鼠肝组织中糖原磷酸化酶(GP)、糖原脱分支酶(GDBE)和环磷酸腺苷(cAMP)表达水平,降低血清胰高血糖素水平。结论小檗碱可以调控cAMP/GP信号通路,改善db/db小鼠的肝糖原结构,修复受损糖原结构,这可能是其调节肝糖代谢,改善糖尿病症状的机制之一。     

Increased activation of the fear neurocircuitry in children exposed to violence

Most studies investigating the effect of childhood trauma on the brain are retrospective and mainly focus on maltreatment, whereas different types of trauma exposure such as growing up in a violent neighborhood, as well as developmental stage, could have differential effects on brain structure and function. The current magnetic resonance imaging study assessed the effect of trauma exposure broadly and violence exposure more specifically, as well as developmental stage on the fear neurocircuitry in 8‐ to 14‐year‐old children and adolescents (N = 69). We observed reduced hippocampal and increased amygdala volume with increasing levels of trauma exposure. Second, higher levels of violence exposure were associated with increased activation in the amygdala, hippocampus, and ventromedial prefrontal cortex during emotional response inhibition. This association was specifically observed in children younger than 10 years. Finally, increased functional connectivity between the amygdala and brainstem was associated with higher levels of violence exposure. Based on the current findings, it could be hypothesized that trauma exposure during childhood results in structural changes that are associated with later risk for psychiatric disorders. At the same time, it could be postulated that growing up in an unsafe environment leads the brain to functionally adapt to this situation in a way that promotes survival, where the long‐term costs or consequences of these adaptations are largely unknown and an area for future investigations.     

阳春砂小花假合蕊柱的形成过程

目的:研究阳春砂小花假合蕊柱的形成过程。方法:将阳春砂小花自0. 5 cm长度至开花后一天划分为8个生长时期,对小花鲜样解剖并制作石蜡切片,测定花药腔的高度,花粉囊裂口夹角,花粉囊缝隙宽度,花柱直径,花丝与唇瓣的夹角(α),花丝与花药的夹角(β)。结果:花粉囊夹角在开花前无明显变化,开花时从32°缩小为17°。两对花粉囊间的缝隙宽度在第5时期增大至约0. 29 mm,同时期的花柱直径约0. 32 mm,两者比例达92%。相比开花前一天,开花时α角从83°减小为42°,β角从186°减小为147°。花丝的远轴侧比近轴侧多1至5层细胞,花柱的近轴侧比远轴侧多1至6层细胞。结论:远、近轴侧细胞结构的不对称性是花丝、花柱运动的基础。在第5时期,花粉囊间的缝隙增大至几乎与花柱等径,花柱运动嵌入花粉囊间。开花时花粉囊夹角缩小,将花粉囊间隙出口封闭,花柱留在花粉囊间,同时角α,β剧烈减小,雄蕊将雌蕊夹在其中向唇瓣弯曲,最终形成半包于唇瓣内的假合蕊柱结构。     

浅色脂溢性角化症特殊皮肤镜表现一例

患者，女，57岁。躯干部白色丘疹3年。本例皮肤镜表现独特之处在偏振光浸润模式下与典型脂溢性角化病不同，由于色素减退，皮沟与皮嵴表现为浅褐色背景下放射状分布亮白色线状条纹，呈珊瑚样结构。