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.     

Effect of Day Optimizing Throughput (Dot) Knee Software Implementation on Magnetic Resonance Imaging Workflow Efficiency

PurposeAttempts by magnetic resonance (MR) manufacturers to help imaging centres improve patient throughput has led to the development of more automated acquisition. This software is capable of customizing individual scan alignment; potentially improving imaging efficiency and standardizing protocols. However, substantial investments are required to introduce such systems, potentially deterring their widespread application. This study assessed the implementation costs and reduction in examination durations for automated knee MR imaging (MRI) software.Materials and MethodsResearch activities were performed at a community-based academic centre on a 3-Tesla (3-T) system using Siemens' Day Optimizing Throughput (Dot) knee software. Examination acquisition times were extracted from the system before and after software implementation. Fiscal year 2012/13 finances were used to determine the average hourly cost of MRI utilization. Costs associated with automated software implementation were also calculated. Finally, the number of knee scans required to achieve a positive return on investment using the software was established.Results and DiscussionThe mean (standard deviation, sample size) pre- and post-Dot software scan times were 23.20 (4.18, n = 266) and 21.94 (4.51, n = 59) minutes, respectively, for a routine knee scan and 11.88 (1.60, n = 74) and 11.24 (1.51, n = 27) minutes, respectively, for a fast knee scan. The overall weighted average resulted in a 64-second time savings per automated knee examination. This negligible time savings would be extremely difficult to make use of clinically. Dot simplified 29 unique knee protocols to two, improving the consistency of knee examinations. Current Dot software is not compatible with all patients and therefore has limitations that are a concern among MR technologists.ConclusionAdoption of automated knee systems could assist in standardizing protocols; however, the cost of implementation and difficulty in modifying patient scheduling to reflect the minimal time savings would make a financial return unlikely to occur at small- and medium-sized institutions.     

Fertility Outcome After Renal Transplantation: A Single-Center Experience

BackgroundWomen suffering from kidney disease are more prone to fertility problems, due to uremia. Fortunately, their fertility rate increases dramatically after renal transplantation. This study analyzes the predictors/risk factors of successful pregnancy with live birth outcome while presenting an overview of the 7-year experience of a single center.MethodsThis retrospective cohort study includes 239 women of reproductive age (18–40 years) who underwent renal transplantation in a tertiary Turkish clinic between October 1, 2011, and August 24, 2017. The subjects were invited to take part in a survey questioning their obstetric characteristics and they were assessed in 2 groups: fertile and infertile. Multivariable linear regression analysis was conducted to determine the predictors of a successful pregnancy.ResultsThirty-five 35 patients wished to become pregnant: 12 got pregnant spontaneously, while 21 failed to become pregnant (spontaneously). The mean age of the patients at the survey was 34 ± 7. Regular menstrual cycles after renal transplantation, tacrolimus-mycophenolate mofetil maintenance protocol, and age at transplantation were found to be predictors of spontaneous pregnancy. The duration of peritoneal dialysis was significantly longer in the infertile group (48 vs 12 months).ConclusionEnd-stage renal disease's negative impacts, including menstrual abnormality and fertility problems, can be overcome by successful kidney transplantation with appropriate immunosuppression. Minimizing the duration of peritoneal dialysis, particularly in patients who desire future fertility, may be accepted as a logical management strategy.     

Switch From Twice-daily Tacrolimus to Once-daily,Prolonged-release Tacrolimus in Kidney Transplantation: Long-term Outcome

Background

One daily dose of tacrolimus (QDT) improves adherence in kidney transplant (KT) recipients. A switch from twice-daily tacrolimus (BDT) to QDT showed similar efficacy and safety.

Herzoperationen wegen Herztumoren in Deutschland – Ergebnisse eienr Umfrage für das Jahr 1996

Zusammenfassung Zahlen zur H?ufigkeit von Herztumoren im operativen Krankengut liegen bisher für die Bundesrepublik Deutschland nicht vor. Um einen entsprechenden überblick für das Jahr 1996 zu erhalten, wurde allen 77 herzchirurgischen Zentren der Bundesrepublik Deutschland ein standardisierter Fragebogen zugesandt. Daten von 65 der 77 Herzzentren (=84%) waren schlie?lich verfügbar: 187 Patienten waren wegen Myxomen, lediglich 44 wegen nichtmyxomat?sen Tumoren, davon 28 wegen malignen prim?ren oder sekund?ren Herztumoren, operiert worden. Im Jahr 1996 waren somit 0,32% (231/72 763) der Eingriffe mit Herz-Lungen-Maschine (erfa?t 72 763 von insgesamt 87 372) wegen eines Herztumors vorgenommen worden. Ausgehend von diesen operativen Daten liegt die Inzidenz ausschlie?lich der prim?ren Tumoren des Herzens zumindest bei 3 Tumoren pro 1 Million Einwohner pro Jahr (253 Tumoren/81,814 Millionen Einwohner). Wenn auch kleine Tumoren asymptomatisch und unentdeckt bleiben k?nnen, wird heute doch die Mehrzahl prim?rer kardialer Tumoren durch Echokardiographie, Computer- und Kernspintomographie bereits zu Lebzeiten des Patienten diagnostiziert, und diese Patienten werden in aller Regel einer Operation zugeführt. Somit werden gut 0,3% aller Eingriffe mit Herz-Lungen-Maschine in Deutschland wegen Herztumoren durchgeführt, wobei es sich weit überwiegend um Myxome handelt. Eingegangen: 23. September 1997, Akzeptiert: 11. Februar 1998     

Krankheitsprognose,psychosoziale Belastung und Einstellung von Melanompatienten zu unterstützenden psychotherapeutischen Maßnahmen

Zusammenfassung Bei 205 Melanompatienten im Stadium I und II wurden das Ausma? der psychosozialen Belastung und der sozialen Unterstützung sowie die Einstellung der Patienten zu unterstützenden Gespr?chsangeboten erhoben. 59% der Patienten fanden zus?tzliche unterstützende Gespr?che mit dem behandelnden Dermatologen, 20% mit einem Psychotherapeuten sinnvoll. Patienten, die starke Angst vor einem Fortschreiten des Tumors ?u?erten und die sich über die Erkrankung nicht ausreichend aufgekl?rt fühlten, wünschten Gespr?che mit dem behandelnden Arzt. Patienten, die sich psychosozial st?rker belastet fühlten und sozial weniger Unterstützung durch ihr soziales Umfeld angaben, befürworteten Unterstützung durch einen Psychotherapeuten. Auch eine ungünstige Prognose scheint das Interesse an psychotherapeutischer Unterstützung zu verst?rken. Eingegangen am 13. Januar 1995 Angenommen am 23. August 1995     

汉语失写症的神经心理学研究及其意义

目的 探讨汉语失写症的神经心理语言学机制以及该研究对于汉语失写症病理行为的康复学意义。方法 采用汉语失语检查法和汉语失写检查法测试口语和书写能力，详细记录患者的书写、失写行为特征，区分言语障碍类型；运用计算机图像处理技术对病灶CT／MRI图像进行标准化、二维叠加、三维重建等处理，并与非失写对照组相减，显示不同失写类型病变的集中趋势。结果 左侧半球损害48例，其中失语30例，失写32例，后者中纯失写1例，失读并失写1例；右侧半球损害15例，其中失语失写3例。具体的资料分析表明：不同的失写类型有不同的病理行为特点。计算机图像处理结果显示：失语性失写病灶较集中的区域为左额顶叶深部白质。惰性失写主要集中在左外侧裂的前方、从额中下回向后部延伸。镜像书写则分散于左丘脑、基底节附近。结论 汉语失写症的病理行为特点与病损定位有密切的关系；双通道理论有可能符合汉语语言学机制；汉语失写症的神经心理学研究对汉语失写康复模式的制定有重要意义。