Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial.

Importance: SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates lung injury in preclinical models, although data in humans with COVID-19 remain mixed.

Objective: To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19.

Cinematic virtual reality for anxiety management in mechanically ventilated patients: a feasibility and pilot study.

Background: Mechanically ventilated patients experience anxiety for many reasons. Pharmacological treatments such as benzodiazepines are commonly employed to manage anxiety; however, these therapies often cause undesired side effects. Additional therapies for anxiety management are needed.

Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy.

Objectives: To determine whether IV vitamin C therapy reduces 28-day mortality in patients with septic shock.

Design: Multicenter, double-blinded, randomized controlled trial.

Setting: One academic medical ICU and four community ICUs.

A multi-center phase II randomized clinical trial of losartan on symptomatic outpatients with COVID-19.

Background: The SARS-CoV-2 virus enters cells via Angiotensin-converting enzyme 2 (ACE2), disrupting the renin-angiotensin-aldosterone axis, potentially contributing to lung injury. Treatment with angiotensin receptor blockers (ARBs), such as losartan, may mitigate these effects, though induction of ACE2 could increase viral entry, replication, and worsen disease.

Methods: This study represents a placebo-controlled blinded randomized clinical trial (RCT) to test the efficacy of losartan on outpatients with COVID-19 across three hospital systems with numerous community sites in Minnesota, U.

Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions.

CCCTC binding factor (CTCF) is involved in organizing chromosomes into mega base-sized, topologically associated domains (TADs) along with other factors that define sub-TAD organization. CTCF-Cohesin interactions have been shown to be critical for transcription insulation activity as it stabilizes long-range interactions to promote proper gene expression. Previous studies suggest that heterochromatin boundary activity of CTCF may be independent of Cohesin, and there may be additional mechanisms for defining topological domains.

Shock.

Critically ill patients with undifferentiated shock are complex and challenging cases in the ED. A systematic approach to assessment and management is essential to prevent unnecessary morbidity and mortality. The simplified, systematic approach described in this article focuses on determining the presence of problems with cardiac function (the pump), intravascular volume (the tank), or systemic vascular resistance (the pipes).

From sextant to GPS: twenty-five years of mapping the genome with ChIP.

Since its inception, ChIP technology has evolved immensely. Technological advances have improved its specificity and sensitivity, its scale has expanded to a genome-wide level, and its relative ease of use has made it a virtually ubiquitous tool. This year marks the 25th anniversary of the development of ChIP.

The DNA binding and catalytic domains of poly(ADP-ribose) polymerase 1 cooperate in the regulation of chromatin structure and transcription.

We explored the mechanisms of chromatin compaction and transcriptional regulation by poly(ADP-ribose) polymerase 1 (PARP-1), a nucleosome-binding protein with an NAD(+)-dependent enzymatic activity. By using atomic force microscopy and a complementary set of biochemical assays with reconstituted chromatin, we showed that PARP-1 promotes the localized compaction of chromatin into supranucleosomal structures in a manner independent of the amino-terminal tails of core histones. In addition, we defined the domains of PARP-1 required for nucleosome binding, chromatin compaction, and transcriptional repression.

Regulation of chromatin structure and chromatin-dependent transcription by poly(ADP-ribose) polymerase-1: possible targets for drug-based therapies.

Poly(ADP-ribose) Polymerase-1 (PARP-1) is the prototypical and most abundantly expressed member of a family of PARPs that catalyze the polymerization of ADP-ribose (ADPR) units from donor NAD' molecules on target proteins. PARP-1 plays roles in a variety of genomic processes, including the regulation of chromatin structure and transcription in response to specific cellular signals. PARP-1 also plays important roles in many stress-induced disease states.

Specific contributions of histone tails and their acetylation to the mechanical stability of nucleosomes.

The distinct contributions of histone tails and their acetylation to nucleosomal stability were examined by mechanical disruption of individual nucleosomes in a single chromatin fiber using an optical trap. Enzymatic removal of H2A/H2B tails primarily decreased the strength of histone-DNA interactions located approximately +/-36bp from the dyad axis of symmetry (off-dyad strong interactions), whereas removal of the H3/H4 tails played a greater role in regulating the total amount of DNA bound. Similarly, nucleosomes composed of histones acetylated to different degrees by the histone acetyltransferase p300 exhibited significant decreases in the off-dyad strong interactions and the total amount of DNA bound.