Discovery of miRNA-mRNA regulatory networks in glioblastoma reveals novel insights into tumor microenvironment remodeling.

Adult glioblastoma (GBM) is a highly aggressive primary brain tumor, accounting for nearly half of all malignant brain tumors, with a median survival rate of only 8 months. Treatment for GBM is largely ineffective due to the highly invasive nature and complex tumor composition of this malignancy. MicroRNAs (miRNA) are short, non-coding RNAs that regulate gene expression by binding to messenger RNAs (mRNA).

The lateral septum returns to the center stage of brain reward.

In this issue of Neuron, Chen et al. found that lateral septum Esr1-expressing cells respond to both non-drug and drug rewards. Mice will lever press for optogenetic stimulation of these neurons, which are also critical to methamphetamine locomotor sensitization, conditioned place preference, self-administration, and reinstatement.

INPP4B promotes PDAC aggressiveness via PIKfyve and TRPML-1-mediated lysosomal exocytosis.

Aggressive solid malignancies, including pancreatic ductal adenocarcinoma (PDAC), can exploit lysosomal exocytosis to modify the tumor microenvironment, enhance motility, and promote invasiveness. However, the molecular pathways through which lysosomal functions are co-opted in malignant cells remain poorly understood. In this study, we demonstrate that inositol polyphosphate 4-phosphatase, Type II (INPP4B) overexpression in PDAC is associated with PDAC progression.

The LCLAT1/LYCAT acyltransferase is required for EGF-mediated phosphatidylinositol-3,4,5-trisphosphate generation and Akt signaling.

Receptor tyrosine kinases such as EGF receptor (EGFR) stimulate phosphoinositide 3 kinases to convert phosphatidylinositol-4,5-bisphosophate [PtdIns(4,5)P] into phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P]. PtdIns(3,4,5)P then remodels actin and gene expression, and boosts cell survival and proliferation. PtdIns(3,4,5)P partly achieves these functions by triggering activation of the kinase Akt, which phosphorylates targets like Tsc2 and GSK3β.

A rat model of operant negative reinforcement in opioid-dependent males and females.

Rationale And Objective: Avoidance of opioid withdrawal plays a key role in human opioid addiction. Here, we present a procedure for studying operant negative reinforcement in rats that was inspired by primate procedures where opioid-dependent subjects lever-press to prevent naloxone infusions.

Methods: In Experiment 1, we trained rats (n = 30, 15 females) to lever-press to escape and then avoid mild footshocks (0.

Factors associated with unintended perianesthesia hypothermia.

Background: Our hypothesis was that total intravenous anesthesia (TIVA) is associated with an increase in hypothermia.

Methods: Inclusion criteria were patients from the National Anesthesia Clinical Outcomes Registry undergoing a general anesthetic during 2019. Data collected included patient age, sex, American Society of Anesthesiologists physical status classification system score (ASAPS), duration of anesthetic, use of TIVA, type of procedure, and hypothermia.

Different Effects of Peer Sex on Operant Responding for Social Interaction and Striatal Dopamine Activity.

When rats are given discrete choices between social interactions with a peer and opioid or psychostimulant drugs, they choose social interaction, even after extensive drug self-administration experience. Studies show that like drug and nondrug food reinforcers, social interaction is an operant reinforcer and induces dopamine release. However, these studies were conducted with same-sex peers.

Sugammadex and blood loss during cervical spine fusion surgery.

Background And Aims: Sugammadex (SUG) has been associated with changes in coagulation studies. Most reports have concluded a lack of clinical significance based on surgical blood loss with SUG use at the end of surgery. Previous reports have not measured its use intraoperatively during ongoing blood loss.

Functional recovery in a cohort of ECMO and non-ECMO acute respiratory distress syndrome survivors.

Background: The mortality benefit of VV-ECMO in ARDS has been extensively studied, but the impact on long-term functional outcomes of survivors is poorly defined. We aimed to assess the association between ECMO and functional outcomes in a contemporaneous cohort of survivors of ARDS.

Methods: Multicenter retrospective cohort study of ARDS survivors who presented to follow-up clinic.

mRNAs encoding self-DNA reactive cGAS enhance the immunogenicity of lipid nanoparticle vaccines.

Nucleic acid-based vaccines hold promise in preventing infections and treating cancer. The most common use of this technology is to encode antigenic proteins on mRNAs that are delivered to cells via lipid nanoparticle (LNP) formulations. In this study, we discovered that immunostimulatory proteins can also be encoded on mRNAs in LNPs.

Trajectory of PaO/FiO Ratio in Shock After Angiotensin II.

Introduction: High-dose catecholamines can impair hypoxic pulmonary vasoconstriction and increase shunt fraction. We aimed to determine if Angiotensin II (Ang-2) is associated with improved PaO/FiO and SpO/FiO in patients in shock.

Methods: Adult patients at four tertiary care centers and one community hospital in the United States who received Ang-2 from July 2018-September 2020 were included in this retrospective, observational cohort study.

Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial.

Background: High dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes in patients treated with angiotensin II (AT II).

Methods: Exploratory post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial data.

Role of Piriform Cortex and Its Afferent Projections in Relapse to Fentanyl Seeking after Food Choice-Induced Voluntary Abstinence.

We previously demonstrated a role of piriform cortex (Pir) in relapse to fentanyl seeking after food choice-induced voluntary abstinence. Here, we used this model to further study the role of Pir and its afferent projections in fentanyl relapse. We trained male and female rats to self-administer palatable food pellets for 6 d (6 h/day) and fentanyl (2.

Raising the bar on fibrinogen: a retrospective assessment of critical hypofibrinogenemia in severely injured trauma patients.

Objectives: Fibrinogen depletion may occur at higher levels than historically referenced. We evaluated hypofibrinogenemia and associated mortality and multiple organ failure (MOF) after severe injury.

Methods: Retrospective investigation including 417 adult patients with Injury Severity Score (ISS) >15.

Effect of Selective Lesions of Nucleus Accumbens µ-Opioid Receptor-Expressing Cells on Heroin Self-Administration in Male and Female Rats: A Study with Novel Knock-in Rats.

The brain µ-opioid receptor (MOR) is critical for the analgesic, rewarding, and addictive effects of opioid drugs. However, in rat models of opioid-related behaviors, the circuit mechanisms of MOR-expressing cells are less known because of a lack of genetic tools to selectively manipulate them. We introduce a CRISPR-based knock-in transgenic rat that provides cell type-specific genetic access to MOR-expressing cells.

Role of ventral subiculum neuronal ensembles in incubation of oxycodone craving after electric barrier-induced voluntary abstinence.

High relapse rate is a key feature of opioid addiction. In humans, abstinence is often voluntary due to negative consequences of opioid seeking. To mimic this human condition, we recently introduced a rat model of incubation of oxycodone craving after electric barrier-induced voluntary abstinence.

Angiotensin II for Vasodilatory Hypotension in Patients Requiring Mechanical Circulatory Support.

Patients supported on mechanical circulatory support devices experience vasodilatory hypotension due to high surface area exposure to nonbiological and non-endothelialized surfaces. Angiotensin II has been studied in general settings of vasodilatory shock, however concerns exist regarding the use of this vasopressor in patients with pre-existing cardiac failure. The objective of this study was to assess the systemic and central hemodynamic effects of angiotensin II in patients with primary cardiac or respiratory failure requiring treatment with mechanical circulatory support devices.

The Protective Effect of Social Reward on Opioid and Psychostimulant Reward and Relapse: Behavior, Pharmacology, and Brain Regions.

Until recently, most modern neuroscience research on addiction using animal models did not incorporate manipulations of social factors. Social factors play a critical role in human addiction: social isolation and exclusion can promote drug use and relapse, while social connections and inclusion tend to be protective. Here, we discuss the state of the literature on social factors in animal models of opioid and psychostimulant preference, self-administration, and relapse.

Thromboelastography Parameters do not Discriminate for Thrombotic Events in Hospitalized Patients With COVID-19.

Background: Coronavirus disease 2019 (COVID-19) is associated with a prothrombotic state; leading to multiple sequelae. We sought to detect whether thromboelastography (TEG) parameters would be able to detect thromboembolic events in patients hospitalized with COVID-19.

Methods: We performed a retrospective multicenter case-control study of the Collaborative Research to Understand the Sequelae of Harm in COVID (CRUSH COVID) registry of 8 tertiary care level hospitals in the United States (US).

Socioeconomic Disparities in Method of Anesthesia for Knee Arthroplasties in the US.

Introduction: Knee arthroplasty (KA) can be performed using general anesthesia (GA), neuraxial anesthesia (NA) or regional anesthesia (RA). We believe proportion of types of anesthetics have changed but that there is a disparity based on socioeconomic factors.

Methods: Unadjusted rates and adjusted odds ratios for the use of RA or PNB were compared between groupings of patients based on socioeconomic status.

Increased Serum Mir-150-3p Expression Is Associated with Radiological Lung Injury Improvement in Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by the SARS-CoV-2 virus, responsible for an atypical pneumonia that can progress to acute lung injury. MicroRNAs are small non-coding RNAs that control specific genes and pathways. This study evaluated the association between circulating miRNAs and lung injury associated with COVID-19.

Racial-ethnic disparities in potentially preventable complications after cesarean delivery in Maryland: an observational cohort study.

Background: Potentially preventable complications are monitored as part of the Maryland Hospital Acquired Conditions Program and are used to adjust hospital reimbursement. Few studies have evaluated racial-ethnic disparities in potentially preventable complications. Our study objective was to explore whether racial-ethnic disparities in potentially preventable complications after Cesarean delivery exist in Maryland.