Duo-Chol: A Photoconvertible Live Cell Imaging Tool for Tracking Cholesterol.

Investigating cholesterol trafficking pathways continues to be of significant scientific interest owing to its homeostasis being associated with several debilitating cardiovascular and neurodegenerative diseases including atherosclerosis, Niemann-Pick's disease, Alzheimer's disease, and Parkinson's disease. To further our understanding of cholesterol trafficking, it is imperative to develop new fluorescent probes that possess improved photostability, low efflux, and high spatial and temporal resolution for live-cell imaging. In this study, we developed a photoconvertible fluorescent cholesterol analog, Duo-Chol, enabling the improved spatiotemporal fluorescence imaging of the dynamic localization of cholesterol in live cells. This tool provides a unique and powerful approach to interrogating cholesterol dynamics, addressing the limitations of existing methods, and expanding our ability to probe the biological role of sterols in living cells.

An adult clock component links circadian rhythms to pancreatic ß-cell maturation.

How ubiquitous circadian clocks orchestrate tissue-specific outputs is not well understood. Pancreatic ß cell-autonomous clocks attune insulin secretion to daily energy cycles, and desynchrony from genetic or behavioral disruptions raises type 2 diabetes risk. We show that the transcription factor DEC1, a clock component induced in adult ß cells, coordinates their glucose responsiveness by synchronizing energy metabolism and secretory gene oscillations. Dec1-ablated mice develop lifelong hypo-insulinemic diabetes, despite normal islet formation and intact circadian Clock and Bmal1 activators. DEC1, but not CLOCK/BMAL1, binds maturity-linked genes that mediate respiratory metabolism and insulin exocytosis, and Dec1 loss disrupts their transcription synchrony. Accordingly, ß-cell Dec1 ablation causes hypo-insulinemia due to immature glucose responsiveness, dampening insulin rhythms. Thus, Dec1 links circadian clockwork to the ß-cell maturation process, aligning metabolism to diurnal energy cycles.

Clinical characteristics and prognostic risk factors of healthcare-associated pneumonia in a Korean tertiary teaching hospital.

The 2016 American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA) guidelines removed the concept of healthcare-associated pneumonia (HCAP). We examined whether the 2016 ATS/IDSA guidelines are applicable in Korea.We conducted a retrospective, observational study of pneumonia patients who were hospitalized at a tertiary teaching hospital from March 2012 to February 2014. Identified pathogens that were not susceptible to ß-lactams, macrolides, and fluoroquinolones were defined as community-acquired pneumonia drug-resistant pathogens (CAP-DRPs). We analyzed the risk factors for 28-day mortality and the occurrence rate of CAP-DRPs.Of the 1046 patients, 399 were classified with HCAP and 647 with CAP. HCAP patients were older and had more comorbidities than CAP patients. Initial pneumonia severity index (PSI) was higher in patients with HCAP than with CAP. HCAP was associated with not only an increased rate of CAP-DRPs (HCAP, 19.8%; CAP, 4.0%; P < .001) but also an increased rate of inappropriate initial antibiotic therapy (IIAT) (HCAP, 16.8%; CAP, 4.6%; P < .001). HCAP was also associated with an increased 28-day mortality rate compared with CAP (HCAP, 14.5%; CAP, 6.3%; P < .001). In a multivariable analysis, PSI was an independent risk factor for 28-day mortality in HCAP patients (odds ratio 1.02, 95% confidence interval 1.01-1.04). CAP-DRPs and IIAT were not associated with mortality.Patients with HCAP revealed higher rates of CAP-DRPs, IIAT, and mortality than patients with CAP. However, CAP-DRPs and IIAT were not associated with mortality. PSI was the main predictive factor for 28-day mortality in patients with HCAP.