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.     

Diet and nutrition against inflammatory bowel disease: Trick or treat(ment)?

Even if the relationships between nutrition and inflammatory bowel disease (IBD) remain underexplored, the current literature is providing, day by day, much more evidence on the effects of various diets in both prevention and treatment of such illnesses. Wrong dietary habits, together with other environmental factors such as pollution, breastfeeding, smoke, and/or antibiotics, are among the theoretical pathogenetic causes of IBD, whose multifactorial aetiology has been already confirmed. While some of these risk factors are potentially reversible, some others cannot be avoided, and efficient treatments become necessary to prevent IBD spread or recurrence. Furthermore, the drugs currently available for treatment of such disease provide low-to-no effect against the symptoms, making the illnesses still strongly disabling. Whether nutrition and specific diets will prove to effectively interrupt the course of IBD has still to be clarified and, in this sense, further research concerning the applications of such dietary interventions is still needed.     

Machine learning models for Parkinson’s disease detection and stage classification based on spatial-temporal gait parameters

BackgroundParkinson’s disease (PD) is a chronic and progressive neurodegenerative disease with no cure, presenting a challenging diagnosis and management. However, despite a significant number of criteria and guidelines have been proposed to improve the diagnosis of PD and to determine the PD stage, the gold standard for diagnosis and symptoms monitoring of PD is still mainly based on clinical evaluation, which includes several subjective factors. The use of machine learning (ML) algorithms in spatial-temporal gait parameters is an interesting advance with easy interpretation and objective factors that may assist in PD diagnostic and follow up.Research questionThis article studies ML algorithms for: i) distinguish people with PD vs. matched-healthy individuals; and ii) to discriminate PD stages, based on selected spatial-temporal parameters, including variability and asymmetry.MethodsGait data acquired from 63 people with PD with different levels of PD motor symptoms severity, and 63 matched-control group individuals, during self-selected walking speed, was study in the experiments.ResultsIn the PD diagnosis, a classification accuracy of 84.6 %, with a precision of 0.923 and a recall of 0.800, was achieved by the Naïve Bayes algorithm. We found four significant gait features in PD diagnosis: step length, velocity and width, and step width variability. As to the PD stage identification, the Random Forest outperformed the other studied ML algorithms, by reaching an Area Under the ROC curve of 0.786. We found two relevant gait features in identifying the PD stage: stride width variability and step double support time variability.SignificanceThe results showed that the studied ML algorithms have potential both to PD diagnosis and stage identification by analysing gait parameters.     

Dorsal suspension for Morton’s neuroma: A comparison with neurectomy

BackgroundThe purpose of this study was to investigate and compare the clinical outcomes of dorsal suspension with those of neurectomy for the treatment of Morton’s neuroma.MethodsWe conducted a retrospective study of dorsal suspension and neurectomy group. The dorsal suspension was performed by dorsal transposition of neuroma over the dorsal transverse ligament after neurolysis. The visual analog scale (VAS), the Foot and Ankle Ability Measure (FAAM), postoperative satisfaction, and complications were evaluated.ResultsBoth groups reported significant pain relief, and there were no significant differences between the groups with respect to postoperative pain. The postoperative FAAM outcomes showed no significant between-group differences. Satisfaction analysis showed ‘excellent’ and ‘good’ results in the dorsal suspension and neurectomy groups (95% and 77.7%, respectively). Complications of numbness and paresthesia reported in the dorsal suspension group (5% and 5%, respectively) were significantly fewer than those of neurectomy group (61.1% and 33.3%, respectively) (both, p < .05).ConclusionsWith its favorable results, dorsal suspension can be another operative option for the treatment of Morton’s neuroma.Level of Evidence: Level III, retrospective comparative case series.     

The increase in bone mineral density by bisphosphonate with active vitamin D analog is associated with the serum calcium level within the reference interval in postmenopausal osteoporosis

Objectives: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD).

Methods: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n?=?93, Study 2: n?=?99) were retrospectively analyzed.

Results: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p?r²: 0.088, p?=?.02). While average sCa of the patients was 9.2?mg/dL before treatment, it increased time-dependently to 9.6?mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike’s information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3?mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3?mg/dL (1.5%) was significantly higher than that in patients with sCa <9.3?mg/dL (0.8%, p?=?.038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed.

Conclusion: sCa was associated with an increased LS-BMD by BPs with aVD.     

2009-2019年西安市肺结核流行特征及治疗转归分析

目的 了解2009-2019年西安市肺结核的流行特征及治疗转归情况，为完善西安市肺结核防治策略提供依据。方法 收集2009-2019年《传染病信息管理系统》中登记的肺结核患者病案信息数据，通过描述性研究方法对肺结核流行病学特征和治疗转归情况进行分析。结果 2009-2019年间西安市肺结核年平均发病率为49.06/10万。郊县、郊区、城区肺结核年平均发病率分别为54.13/10万、47.46/10万和46.19/10万；男性发病率是女性的1.85倍。职业分布排在前5位的为农民（47.48%），家政、家务及待业（14.65%），离退人员（9.55%），学生（8.63%）和工人（5.23%）。利福平敏感或耐药性未知患者的成功治疗率平均为98.03%，利福平耐药患者治疗成功率为51.47%。结论 西安市近年来肺结核发病率和治疗率呈增长趋势，利福平耐药患者治疗成功率较低，要加强对重点人群的健康促进工作，加大肺结核发现力度及患者治疗管理工作。