Towards Improved Peptidic α-Ketoamide Inhibitors of the Plasmodial Subtilisin-Like SUB1: Exploration of N-Terminal Extensions and Cyclic Constraints.

After more than 15 years of decline, the Malaria epidemy has increased again since 2017, reinforcing the need to identify drug candidates active on new targets involved in at least two biological stages of the Plasmodium life cycle. The SUB1 protease, which is essential for parasite egress in both hepatic and blood stages, would meet these criteria. We previously reported the structure-activity relationship analysis of α-ketoamide-containing inhibitors encompassing positions P4-P2'.

Detecting Intrathoracic Airway Closure during Prehospital Cardiopulmonary Resuscitation Using Quasi-Static Pressure-Volume Curves: A Pilot Study.

Intrathoracic airway closure frequently occurs during cardiac arrest, possibly impairing ventilation. Previously, capnogram analysis was used to detect this pathophysiological process. In other populations, quasi-static pressure-volume curves obtained during constant low-flow inflations are routinely used to detect intrathoracic airway closure.

Direct Laser Cooling of Rydberg Atoms with an Isolated-Core Transition.

We propose a scheme to directly laser cool Rydberg atoms by laser cooling the residual ion core within the Rydberg-electron orbit. The scheme is detailed for alkaline-earth-metal Rydberg atoms, whose ions can be easily laser cooled. We demonstrate that a closed optical cooling cycle can be found despite the perturbations caused by the Rydberg electron and that this cycle can be driven over more than 100  μs to achieve laser cooling.

Explorative study on lower inflection point dynamics during cardiopulmonary resuscitation: Potential implications for airway management.

Introduction: In patients undergoing cardiopulmonary resuscitation (CPR) after an Out-of-Hospital Cardiac Arrest (OHCA), intrathoracic airway closure can impede ventilation, adversely affecting patient outcomes. This explorative study investigates the evolution of intrathoracic airway closure by analyzing the lower inflection point (LIP) during the inspiration phase of CPR, aiming to identify the potential thresholds for alveolar recruitment.

Methods And Materials: Eleven OHCA patients undergoing CPR with endotracheal intubation and manual bag ventilation were included.

Insights from structure-activity relationships and the binding mode of peptidic α-ketoamide inhibitors of the malaria drug target subtilisin-like SUB1.

Plasmodium multi-resistance, including against artemisinin, seriously threatens malaria treatment and control. Hence, new drugs are urgently needed, ideally targeting different parasitic stages, which are not yet targeted by current drugs. The SUB1 protease is involved in both hepatic and blood stages due to its essential role in the egress of parasites from host cells, and, as potential new target, it would meet the above criteria.