A time-series analysis examining implementation strategies to increase use of an early-supported discharge hospital at home model.

Background: Early-supported discharge (ESD) hospital-at-home (HaH) programs facilitate hospitalized patients to receive ongoing acute-level care at home, thereby promoting patient-centeredness while improving hospital throughput.

Objectives: The current study aimed to test multiple implementation strategies to increase and sustain HaH ESD utilization.

Methods: We conducted interrupted time series analyses to evaluate the effectiveness of implementation strategies on weekly HaH ESD referrals and capacity utilization at five hospitals.

Replacement substance P reduces cardiac fibrosis in monkeys with type 2 diabetes.

Background: Type 2 diabetes mellitus (T2DM)-associated cardiac fibrosis contributes to heart failure. We previously showed that diabetic mice with cardiomyopathy, including cardiac fibrosis, exhibit low levels of the neuropeptide substance P; exogenous replacement of substance P reversed cardiac fibrosis, independent of body weight, blood glucose and blood pressure. We sought to elucidate the effectiveness and safety of replacement substance P to ameliorate or reverse cardiac fibrosis in type 2 diabetic monkeys.

Itaconate and Its Derivatives Repress Early Myogenesis and .

A Krebs cycle intermediate metabolite, itaconate, has gained attention as a potential antimicrobial and autoimmune disease treatment due to its anti-inflammatory effects. While itaconate and its derivatives pose an attractive therapeutic option for the treatment of inflammatory diseases, the effects outside the immune system still remain limited, particularly in the muscle. Therefore, we endeavored to determine if itaconate signaling impacts muscle differentiation.

It takes two (Las1 HEPN endoribonuclease domains) to cut RNA correctly.

The ribosome biogenesis factor Las1 is an essential endoribonuclease that is well-conserved across eukaryotes and a newly established member of the higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain-containing nuclease family. HEPN nucleases participate in diverse RNA cleavage pathways and share a short HEPN nuclease motif (RφH) important for RNA cleavage. Most HEPN nucleases participate in stress-activated RNA cleavage pathways; Las1 plays a fundamental role in processing pre-rRNA.

Cryo-EM reveals active site coordination within a multienzyme pre-rRNA processing complex.

Ribosome assembly is a complex process reliant on the coordination of trans-acting enzymes to produce functional ribosomal subunits and secure the translational capacity of cells. The endoribonuclease (RNase) Las1 and the polynucleotide kinase (PNK) Grc3 assemble into a multienzyme complex, herein designated RNase PNK, to orchestrate processing of precursor ribosomal RNA (rRNA). RNase PNK belongs to the functionally diverse HEPN nuclease superfamily, whose members rely on distinct cues for nuclease activation.