Biosynthesis and structure assignment of a hydroxylated metabolite of the orexin-1 receptor antagonist JNJ-61393215.

JNJ-61393215, a deuterated compound, is a selective OX1R antagonist. In both preclinical and clinical studies, a hydroxylated metabolite designated M54 was observed to be the most abundant metabolite in plasma. Screening of Hypha PolyCYPs® kit revealed PolyCYP 152 was the most proficient at producing M54 from JNJ-61393215 and subsequent scale up with PolyCYP 152 provided small but sufficient quantities of M54 for initial structure elucidation by NMR analyses.

Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium: A Cluster Randomized Crossover Trial.

Importance: Delirium is common after cardiac surgery and associated with adverse outcomes. Intraoperative benzodiazepines may increase postoperative delirium but restricting intraoperative benzodiazepines has not yet been evaluated in a randomized trial.

Objective: To determine whether an institutional policy of restricted intraoperative benzodiazepine administration reduced the incidence of postoperative delirium.

A single arm phase 2 clinical trial of YIV-906 with neoadjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer.

Background: Pre-operative chemoradiation for rectal cancer is often associated with severe gastrointestinal (GI) toxicity which can interrupt, delay, and/or lead to termination of treatment. In this study, we evaluated whether the addition of YIV-906, a novel herbal medicine proven to reduce GI toxicity associated with chemotherapy could also reduce GI side effects during standard pre-operative capecitabine and pelvic radiation therapy (RT) in the neoadjuvant setting for the treatment of locally advanced rectal cancer.

Methods: This single arm clinical study enrolled 24 patients between Dec 23, 2014-Sep 17, 2018 at Smilow Cancer Hospital, a comprehensive cancer center at Yale New Haven Hospital.

Enhancing nursing students' clinical competency using a multi-patient simulation learning model: A randomized controlled study.

Background: For nurses, clinical competency is paramount in ensuring that patients receive safe, high-quality care. Multi-patient simulation (MPS) in nursing education is gaining attention, and evidence shows its suitability for real-life situations. MPS can be an effective solution for nurses' continuing clinical education.

Mesenchymal Stem Cell Exosomes Enhance Posterolateral Spinal Fusion in a Rat Model.

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained.

Non-pharmacological and pharmacological treatments for bone health after stroke: Systematic review with meta-analysis.

Background: Hemi-osteoporosis is a common secondary complication of stroke. No systematic reviews of pharmacological and non-pharmacological agents for post-stroke bone health have estimated the magnitude and precision of effect sizes to guide better clinical practice.

Objectives: To examine the benefits and harms of pharmacological and non-pharmacological agents on bone health in post-stroke individuals.

Characteristics and outcome of a territory-wide cohort study of patients with acquired hemophilia A in Hong Kong.

Introduction: Acquired hemophilia A (AHA) is a rare bleeding disorder with destruction of factor VIII by autoantibodies. Comprehensive data for Chinese patients are lacking. Predictors of hospital stay have not been investigated.

YIV-818-A: a novel therapeutic agent in prostate cancer management through androgen receptor downregulation, glucocorticoid receptor inhibition, epigenetic regulation, and enhancement of apalutamide, darolutamide, and enzalutamide efficacy.

Prostate cancer is the second leading cause of cancer death among men in the United States. Castration-Resistant Prostate Cancer (CRPC) often develops resistance to androgen deprivation therapy. Resistance in CRPC is often driven by AR variants and glucocorticoid receptor (GR).

Right ventricular ejection fraction derived from intraoperative three-dimensional transesophageal echocardiography versus cardiac magnetic resonance imaging.

Purpose: Right ventricle (RV) assessment is critical during cardiac surgery. Traditional assessment consists of visual estimation and measurement of validated parameters. Cardiac magnetic resonance imaging (cMRI) is the gold standard for RV analysis, and transthoracic three-dimensional (3D) echocardiography is validated against this.

Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free): A Protocol for a Multi-centre Randomized Cluster Crossover Trial.

Delirium is common after cardiac surgery and is associated with adverse outcomes. Administration of benzodiazepines before and after cardiac surgery is associated with delirium; guidelines recommend minimizing their use. Benzodiazepine administration during cardiac surgery remains common because of its recognized benefits.

Inhibition of PLK4 remodels histone methylation and activates the immune response via the cGAS-STING pathway in TP53-mutated AML.

Acute myeloid leukemia (AML) with TP53 mutation is one of the most lethal cancers and portends an extremely poor prognosis. Based on in silico analyses of druggable genes and differential gene expression in TP53-mutated AML, we identified pololike kinase 4 (PLK4) as a novel therapeutic target and examined its expression, regulation, pathogenetic mechanisms, and therapeutic potential in TP53-mutated AML. PLK4 expression was suppressed by activated p53 signaling in TP53 wild-type AML and was increased in TP53-mutated AML cell lines and primary samples.

A specific early eluting peak in Bio-Rad Variant II cation-exchange high-performance liquid chromatography (CE-HPLC) for the screening of alpha-thalassaemia in a Chinese population.

The early eluting peaks in the first minute of cation-exchange high-performance liquid chromatography (CE-HPLC) are often not analysed in haemoglobin pattern studies, except for haemoglobin (Hb) Bart's and Hb H peaks. In this study, we described the presence of a specific α-thalassaemia early eluting peak (αEEP) at the retention time of 0.24 min generated by Variant II CE-HPLC (β-Thalassaemia Short Program; Bio-Rad Laboratories).

Systemic Diclofenac Sodium Reduces Postoperative rhBMP-2 Induced Neuroinflammation: A Rodent Model Study.

Study Design: This is a basic science, animal research study.

Objective: This study aims to explore, in rodent models, the effectiveness of systemic nonsteroidal anti-inflammatory drugs in reducing recombinant human bone morphogenetic protein-2 (rhBMP-2) induced neuroinflammation.

Summary Of Background Data: rhBMP-2 is increasingly used to augment fusion in lumbar interbody fusion surgeries, although it can cause complications including postoperative radiculitis.

C-Reactive Protein as a Negative Predictive Marker for Anastomotic Leakage After Minimally Invasive Esophageal Surgery.

Background: Serum C-reactive protein (CRP) is commonly used by surgeons to raise suspicion of anastomotic leakage and other infectious complications, but most studies on optimal cut-off values are retrospective with a small sample of patients. The aim of this study was to determine the accuracy and optimal cut-off value of CRP for anastomotic leakage in patients following esophagectomy for cancer.

Materials And Methods: Consecutive minimally invasive esophagectomy for esophageal cancer patients was included in this prospective study.

Metabolism and disposition of JNJ-10450232 (NTM-006) in rats, dogs, monkeys and humans.

JNJ-10450232 (NTM-006), a novel non-opioid, non-nonsteroidal anti-inflammatory drug with structural similarities to acetaminophen, demonstrated anti-pyretic and/or analgesic activities in preclinical models and humans and reduced potential to cause hepatotoxicity in preclinical species. Metabolism and disposition of JNJ-10450232 (NTM-006) following oral administration to rats, dogs, monkeys and humans are reported. Urinary excretion was the major route of elimination based on recovery of 88.

Perioperative Optimization of the Cardiac Surgical Patient.

Perioperative optimization of cardiac surgical patients is imperative to reduce complications, utilize health care resources efficiently, and improve patient recovery and quality of life. Standardized application of evidence-based best practices can lead to better outcomes. Although many practices should be applied universally to all patients, there are also opportunities along the surgical journey to identify patients who will benefit from additional interventions that will further ameliorate their recovery.

YIV-906 enhances nuclear factor of activated T-cells (NFAT) activity of T cells and promotes immune checkpoint blockade antibody action and CAR T-cell activity.

YIV-906 is a systems biology botanical cancer drug, inspired by a traditional Chinese herbal formulation. Results from eight Phase I/II to II clinical studies demonstrated the potential of YIV-906 to prolong survival and improve the quality of life of cancer patients. As an immunomodulator in the tumor microenvironment, YIV-906 can turn cold tumors hot and potentiate anti-tumor activity for different classes of anticancer agents; and as a cytoprotector in the GI, YIV-906 can reduce non-hematological side effects and speed up damaged tissue recovery.