Design and Optimization of Novel Benzimidazole- and Imidazo[4,5-]pyridine-Based ATM Kinase Inhibitors with Subnanomolar Activities.

The ATM kinase is a promising target in cancer treatment as an important regulator of the cellular response to DNA double-strand breaks. In this work, we present a new class of specific benzimidazole-based ATM inhibitors with picomolar potency against the isolated enzyme and favorable selectivity within relative PIKK and PI3K kinases. We could identify two promising inhibitor subgroups with significantly different physicochemical properties, which we developed simultaneously.

Psychophysics of Pain: A Methodological Introduction.

For over 100 years, psychophysics ..÷ the scientific study between physical stimuli and sensation .

Empathy in Healthcare Professionals during the Coronavirus Pandemic.

Background: Empathy is important for successful interactions. The aim of the present study was to determine whether the cognitive component (Perspective taking) and affective components (Empathic concern and Personal distress) of empathy in health professionals were related to the degree of perceived threat of coronavirus, difficulties in doing work, difficulties in getting along with people, the health condition (current or past coronavirus disease), as well as with some socio-demographic characteristics. Fantasy as the cognitive component of empathy was not the focus of the present study as more irrelevant to clinical practice.

Incidence and Predictors of Inadvertent Dural Puncture After Percutaneous Spinal Cord Stimulation: A Retrospective Database Analysis.

Objectives: Inadvertent dural puncture (IDP) is a known complication associated with traditional neuraxial procedures; however, its characterization after percutaneous spinal cord stimulation (SCS) lead placement has yet to be clearly established in large population studies. This retrospective analysis aims to understand the incidence and associated characteristics of patients with IDP after percutaneous SCS lead placement.

Materials And Methods: The PearlDiver Mariner database of national all-payer claims was used to identify patients who received percutaneous SCS leads and had a claim for IDP (intraoperative IDP or postdural puncture headache [PDPH] claim) within 45 days.

Development of novel urea-based ATM kinase inhibitors with subnanomolar cellular potency and high kinome selectivity.

The ATM kinase is a key molecule regulating DNA damage response and can be targeted resulting in efficient radio- or chemosensitization. Due to the enormous size of this protein and the associated difficulties in obtaining high-quality crystal structures, we sought to develop an accurate in silico model to identify new targeting possibilities. We identified a urea group as the most beneficial chemical anchor point, which could undergo multiple interactions in the aspartate-rich hydrophobic region I of the atypical ATM kinase domain.