Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

SEROPOSITIVITY FOR ASCARIOSIS AND TOXOCARIOSIS AND CYTOKINE EXPRESSION AMONG THE INDIGENOUS PEOPLE IN THE VENEZUELAN DELTA REGION

The present study aimed at measuring seropositivities for infection by Ascaris suum and Toxocara canis using the excretory/secretory (E/S) antigens from Ascaris suum (AES) and Toxocara canis (TES) within an indigenous population. In addition, quantification of cytokine expressions in peripheral blood cells was determined. A total of 50 Warao indigenous were included; of which 43 were adults and seven children. In adults, 44.1% were seropositive for both parasites; whereas children had only seropositivity to one or the other helminth. For ascariosis, the percentage of AES seropositivity in adults and children was high; 23.3% and 57.1%, respectively. While that for toxocariosis, the percentage of TES seropositivity in adults and children was low; 9.3% and 14.3%, respectively. The percentage of seronegativity was comparable for AES and TES antigens in adults (27.9%) and children (28.6%). When positive sera were analyzed by Western blotting technique using AES antigens; three bands of 97.2, 193.6 and 200.2 kDas were mostly recognized. When the TES antigens were used, nine major bands were mostly identified; 47.4, 52.2, 84.9, 98.2, 119.1, 131.3, 175.6, 184.4 and 193.6 kDas. Stool examinations showed that Blastocystis hominis, Hymenolepis nana and Entamoeba coli were the most commonly observed intestinal parasites. Quantification of cytokines IFN-γ, IL-2, IL-6, TGF-β, TNF-α, IL-10 and IL-4 expressions showed that there was only a significant increased expression of IL-4 in indigenous with TES seropositivity (p < 0.002). Ascaris and Toxocara seropositivity was prevalent among Warao indigenous.     

中国精神分裂症患者不同家庭干预措施效果比较的meta分析

目的对中国精神分裂症患者采取家庭干预的研究文献进行综合回顾和系统评价, 比较不同条件下家庭干预效果的差异。方法在中国知网、维普、万方、中国生物医学文献数据库四大中文数据库及OVID Medline、Science Direct、Web of Science、EBSCO四大英文数据库中, 检索各数据库建库至2015年1月为止使用社会功能缺陷筛选量表(SDSS)、简明精神病(科)量表(BPRS)、阳性与阴性症状量表(PANSS)研究中国精神分裂症患者家庭干预效果的文献, 以标准化加权均数差( SMD)作为效应量, 采用meta分析比较不同干预时间、不同干预类型、对不同病程和不同严重程度的精神分裂症患者的家庭干预效果差异。 结果共纳入57篇符合标准的文献。SDSS、PANSS分析结果显示:① 干预时间越长干预效果越好( P < 0.0001、 P=0.0025);② 单独家庭干预比多个家庭合并单独家庭干预的效果更明显( P < 0.0001、 P=0.0131);③ 干预对于病情较重患者效果较好( P < 0.0001、 P=0.0280)。SDSS量表还显示家庭干预对于病程短的患者效果更好( P < 0.0001)。 结论家庭干预更适合病程较短的精神分裂症患者, 干预应实施较长时间; 单独家庭干预更有利于患者阴性症状的改善和社会功能的康复, 且对于病情较轻患者的阴性症状改善效果更好。     

人格特征对男性喉鳞状细胞癌患者术后近期心理状况的影响

目的 探讨人格特征对喉鳞状细胞癌（LSCC）患者术后近期心理健康状况的影响。方法 纳入2017年1月—2019年12月在湖北省肿瘤医院行手术治疗的119例男性LSCC患者，术后5~7 d采用SCL-90、SAS、SDS自评量表评估术后心理状态，采用EPQ问卷测评患者的人格特征。多元线性逐步回归方法分析LSCC患者术后近期SAS和SDS评分的影响因素。结果 男性LSCC患者术后SCL-90、SAS、SDS得分显著高于中国常模（P≤0.05），EPQ中精神质（P）量表和神经质（N）量表得分高于中国常模（P<0.01）。男性LSCC患者术后躯体化、强迫、焦虑、抑郁、敌对、恐怖、偏执、精神病性因子得分均显著高于中国常模（P<0.05）。家庭收入、手术方式、术后近期是否行放化疗、P和N人格特征是术后SAS评分的影响因素（均P<0.01）；家庭收入、手术方式、术后近期是否行放化疗和N人格特征是术后SDS评分的影响因素（P<0.01）。结论 LSCC患者术后近期存在抑郁、焦虑等心理障碍；具有P和N人格特征；家庭收入、手术方式、术后近期是否行放化疗以及P和N人格特征是影响术后SAS及SDS评分的独立危险因素。     

Work hazards and workers’ mental health: an investigation based on the fifth European Working Conditions Survey

Background:Workplace hazards are a significant source of health impairment for workers and of financial losses for firms. EU directives on workers’ health and safety standards significantly contributed to reduce reported occupational injuries, yet the incidence and prevalence of work-related mental illness is still very high.Objectives:We investigated the association between work-related hazards and individuals’ perceived mental health. We reviewed the existing evidence on the channels through which task-related factors, adverse agents and psychosocial factors are expected to affect workers’ health, with specific regard to mental health.Methods:We used data from the fifth wave of the European Working Conditions Survey, covering over 40,000 face-to-face interviews with workers in 34 countries, which includes information on socio-demographic characteristics, firms and jobs attributes, employment status, as well as working conditions and health status. We carried out an empirical analysis with multivariate regression models in order to estimate the relationship between workers’ mental health problems and workplace risk factors.Results:21,020 interviews were used in the multivariate analysis. We found strong correlations between hazards and various indicators of mental health. Among hazardous agents, low temperatures (β=0.0287) and contact with infectious materials (β=0.0394) were positively associated with mental health outcomes. Among task/sequence-related factors, tiring or painful positions (β=0.0713), repetitive hand/arm movements (β=0.0255), working with VDUs (β=0.0301), repetitive tasks <10 min (β=0.0859) and working in evenings (β=0.00754) were positively associated with mental health. Various psychosocial risk factors related to both the content of the job (for example, frequent disruptive interruptions: β=0.219, working in free time: β=0.0759, poor work-life balance: β=0.228) as well as the job context (for example, bad employment prospects: β=0.177, low decisional autonomy: β=0.245, bad social relations: β=0.186, workplace violence: β=0.411) were positively associated with mental health. The main results of the decomposition show that an important contribution to workers’ overall mental distress at work is associated with psychosocial risk factors (up to 60% for depression/anxiety symptoms and sleep disorders), while the contribution of somatic factors is on average lower (up to 20% for overall fatigue).Conclusions:We argue that action is needed to improve workers’ mental well-being, and reduce the economic costs for both the national health system and employers. Regulations and traditional economic measures are unlikely to prove successful in providing adequate standards of primary and secondary preventive measures in the work place without an appropriate and reliable Risk Assessment Procedure.Key words: Work hazards, risk assessment, job content, mental health     

Magnetic resonance elastography with guided pressure waves

Magnetic resonance elastography aims to non-invasively and remotely characterize the mechanical properties of living tissues. To quantitatively and regionally map the shear viscoelastic moduli in vivo, the technique must achieve proper mechanical excitation throughout the targeted tissues. Although it is straightforward, ante manibus, in close organs such as the liver or the breast, which practitioners clinically palpate already, it is somewhat fortunately highly challenging to trick the natural protective barriers of remote organs such as the brain. So far, mechanical waves have been induced in the latter by shaking the surrounding cranial bones. Here, the skull was circumvented by guiding pressure waves inside the subject's buccal cavity so mechanical waves could propagate from within through the brainstem up to the brain. Repeatable, reproducible and robust displacement fields were recorded in phantoms and in vivo by magnetic resonance elastography with guided pressure waves such that quantitative mechanical outcomes were extracted in the human brain.