Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

Sentinel lymph node localization and staging with a low-dose of superparamagnetic iron oxide (SPIO) enhanced MRI and magnetometer in patients with cutaneous melanoma of the extremity - The MAGMEN feasibility study

BackgroundIn patients with melanoma, sentinel lymph node (SLN) status is pivotal for treatment decisions. Current routine for SLN detection combines Technetium^99m (Tc⁹⁹) lymphoscintigraphy and blue dye (BD). The primary aim of this study was to examine the feasibility of using a low dose of superparamagnetic iron oxide (SPIO) injected intracutaneously to detect and identify the SLN, and the secondary aim was to investigate if a low dose of SPIO would enable a preoperative MRI-evaluation of SLN status.MethodsPatients with melanoma of the extremities were eligible. Before surgery, a baseline MRI of the nodal basin was followed by an injection of a low dose (0.02–0.5 mL) of SPIO and then a second MRI (SPIO-MRI). Tc⁹⁹ and BD was used in parallel and all nodes with a superparamagnetic and/or radioactive signal were harvested and analyzed.ResultsFifteen patients were included and the SLNB procedure was successful in all patients (27 SLNs removed). All superparamagnetic SLNs were visualized by MRI corresponding to the same nodes on scintigraphy. Micrometastatic deposits were identified in four SLNs taken from three patients, and SPIO-MRI correctly predicted two of the metastases. There was an association between MRI artefacts in the lymph node and the dose SPIO given.DiscussionIt is feasible to detect SLN in patients with melanoma using a low dose of SPIO injected intracutaneously compared with the standard dual technique. A low dose of SPIO reduces the lymph node MRI artefacts, opening up for a non-invasive assessment of SLN status in patients with cancer.     

MRI图像融合技术在肛瘘评估中的初步应用

目的采用图像融合技术获得T2WI与T2WI-FS的融合图像，评估其在肛瘘及肛周结构显示中的优势。 方法2016年6月至2018年6月，前瞻性选择中山大学附属第一医院29例肛瘘患者进行肛管磁共振（MR）检查，采用图像融合技术获取T2WI与T2WI-FS的融合图像T2WI-Fusion，利用Fisher score算法计算瘘管及肛门括约肌的组织间分辨力Fisher值、脂肪与肛门括约肌间的Fisher值，评估融合图像中瘘管及肛周结构的显示情况。采用改进的双刺激连续质量量表（DSCQS）对T2WI-FS、T2WI、增强3D-VIBE和T2WI-Fusion序列图像进行主观图像质量评价。 结果29例患者均成功获得T2WI与T2WI-FS的融合图像T2WI-Fusion。T2WI-Fusion、T2WI瘘管与括约肌间Fisher均值分别为6.46、3.31，T2WI-Fusion图像对瘘管的显示优于T2WI序列图像（P<0.001）。T2WI-Fusion、T2WI-FS脂肪与括约肌间Fisher均值分别为10.61、2.45，T2WI-Fusion图像对括约肌的显示优于T2WI-FS序列图像（P<0.001）。T2WI-Fusion对瘘管与括约肌的图像质量评价总评分均高于T2WI-FS、T2WI、增强3D-VIBE序列（P<0.001）。 结论MRI图像融合技术同时具备T2WI及T2WI-FS的优势，无需增加扫描序列及扫描时间，且操作简单，花费时间短，显著提高病变及肛周解剖结构的对比度和图像质量。     

Simultaneously recorded intracranial and scalp high frequency oscillations help identify patients with poor postsurgical seizure outcome

ObjectiveHigh frequency oscillations (HFO) between 80–500 Hz are markers of epileptic areas in intracranial and maybe also scalp EEG. We investigate simultaneous recordings of scalp and intracranial EEG and hypothesize that scalp HFOs provide important additional clinical information in the presurgical setting.MethodsSpikes and HFOs were visually identified in all intracranial scalp EEG channels. Analysis of correlation of event location between intracranial and scalp EEG as well as relationship between events and the SOZ and zone of surgical removal was performed.Results24 patients could be included, 23 showed spikes and 19 HFOs on scalp recordings. In 15/19 patients highest scalp HFO rate was located over the implantation side, with 13 patients having the highest scalp and intracranial HFO rate over the same region. 17 patients underwent surgery, 7 became seizure free. Patients with poor post-operative outcome showed significantly more regions with HFO than those with seizure free outcome.ConclusionsScalp HFOs are mostly located over the SOZ. Widespread scalp HFOs are indicative of a larger epileptic network and associated with poor postsurgical outcome.SignificanceAnalysis of scalp HFO add clinically important information about the extent of epileptic areas during presurgical simultaneous scalp and intracranial EEG recordings.