Drug Development.

Background: Progranulin (GRN) plays a critical role in familial frontotemporal dementia (fFTD), where GRN haploinsufficiency leads to reduction in PGRN levels in the brain, resulting in degeneration of neurons in the frontal lobe of brain responsible for personality, language, and behavior. FTD is the most common dementia in people under 60. Sortilin (Sort1), expressed by neurons, endocytoses, and delivers PGRN rapidly to lysosomes for degradation.

Indirect Detection of the Protons in and around Biradicals and their Mechanistic Role in MAS-DNP.

The contribution of protons in or near biradical polarizing agents in Dynamic Nuclear Polarization (DNP) has recently been under scrutiny. Results from selective deuteration and simulations have previously suggested that the role of protons in the biradical molecule depends on the strength of the electron-electron coupling. Here we use the cross effect DNP mechanism to identify and acquire H solid-state NMR spectra of the protons that contribute to propagation of the hyperpolarization, via an experimental approach dubbed Nuclear-Nuclear Double Resonance (NUDOR).

Predicting operative mortality in patients who undergo elective open thoracoabdominal aortic aneurysm repair.

Background: We have developed a model aimed at identifying preoperative predictors of operative mortality in patients who undergo elective, open thoracoabdominal aortic aneurysm (TAAA) repair. We converted this model into an intuitive nomogram to aid preoperative counseling.

Methods: We retrospectively analyzed data from 2884 elective, open TAAA repairs performed between 1986 and 2023 in a single practice.

Enhanced Recovery After Surgery (ERAS) cardiac turnkey order set for perioperative pain management in cardiac surgery: Proceedings from the American Association for Thoracic Surgery (AATS) ERAS Conclave 2023.

Objective: Optimal perioperative pain management is an essential component of perioperative care for the cardiac surgical patient. This turnkey order set is part of a series created by the Enhanced Recovery After Surgery Cardiac Society, first presented at the Annual Meeting of The American Association for Thoracic Surgery in 2023. Several guidelines and expert consensus documents have been published to provide guidance on pain management and opioid reduction in cardiac surgery.

Aurora B inhibition induces hyper-polyploidy and loss of long-term proliferative potential in RB and p53 defective cells.

Polyploidy is a common outcome of chemotherapies, but there is conflicting evidence as to whether polyploidy is an adverse, benign or even favourable outcome. We show Aurora B kinase inhibitors efficiently promote polyploidy in many cell types, resulting in the cell cycle exit in RB and p53 functional cells, but hyper-polyploidy in cells with loss of RB and p53 function. These hyper-polyploid cells (>8n DNA content) are viable but have lost long-term proliferative potential in vitro and fail to form tumours in vivo.