State and Future Science of Opioids and Potential of Biased-ligand Technology in the Management of Acute Pain After Burn Injury.

Pain associated with severe burn injury is one of the most intense and clinically challenging to manage, as the metabolic imbalances associated with the inflammation caused by the injury and treatment interventions (e.g., dressing changes and debridement, excision, and grafting) can further worsen the pain.

Real-world use of inhaled nitric oxide therapy in patients with COVID-19 and mild-to-moderate acute respiratory distress syndrome.

Background: Inhaled nitric oxide (iNO) has been studied in patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 when it may be too late to impact disease course. This article aims to describe real-world iNO use and outcomes in patients with COVID-19 with mild-to-moderate ARDS in the United States.

Methods: This was a retrospective medical chart review study that included patients who were ≥18 years old, hospitalized for COVID-19, met the Berlin ARDS definition, received iNO for ≥24 hours continuously during hospitalization, and had a partial pressure of oxygen (PaO)/fraction of inspired oxygen (FiO) ratio (P/F ratio) of >100 to ≤300 mmHg at iNO initiation.

Mitochondrial deficits in human iPSC-derived neurons from patients with 22q11.2 deletion syndrome and schizophrenia.

Schizophrenia (SZ) is a highly heterogeneous disorder in both its symptoms and risk factors. One of the most prevalent genetic risk factors for SZ is the hemizygous microdeletion at chromosome 22q11.2 (22q11DS) that confers a 25-fold increased risk.

Fate determination of cerebral cortical GABAergic interneurons and their derivation from stem cells.

Cortical GABAergic interneurons modulate cortical excitation, and their dysfunction is implicated in a multitude of neuropsychiatric disorders including autism, schizophrenia and epilepsy. Consequently, the study of cortical interneuron development, and their derivation from stem cells for transplantation therapy, has garnered intense scientific interest. In this review, we discuss some of the molecular signals involved in cortical interneuron fate determination, and describe how this has informed the use of mouse and human embryonic stem cell biology in generating cortical interneurons in vitro.

Assessment of seizure liability of Org 306039, a 5-HT2c agonist, using hippocampal brain slice and rodent EEG telemetry.

Introduction: Evaluation of the seizure potential for a CNS-targeted pharmaceutical compound before it is administered to humans is an important part of development. The current in vitro and in vivo studies were undertaken to characterize the seizure potential of the potent and selective 5-HT2c agonist Org 306039.

Methods: Rat hippocampal slices (n=5) were prepared and Org 306039 was applied over a concentration range of 0-1000μM.

Prenatal deletion of the RNA-binding protein HuD disrupts postnatal cortical circuit maturation and behavior.

The proper functions of cortical circuits are dependent upon both appropriate neuronal subtype specification and their maturation to receive appropriate signaling. These events establish a balanced circuit that is important for learning, memory, emotion, and complex motor behaviors. Recent research points to mRNA metabolism as a key regulator of this development and maturation process.

Nucleoside analog labeling of neural stem cells and their progeny.

Nucleoside analog pulse labeling is an important technique which can assess the birthdate, cell cycle maintenance, or cycling rates of cells during development. This method has evolved over several decades of use and is now applied to a multitude of tissue subtypes and systems. The methodology in this chapter covers the classic uses for analog pulse labeling as well as their use in conjunction with the newly characterized technique of in utero electroporation (IUE).