A threefold superstructure of the anti-epileptic drug phenytoin sodium as a mixed methanol solvate hydrate.

Phenytoin sodium, a salt of 5,5-diphenylimidazolidine-2,4-dione, or phenytoin, is commercially available in various dosage forms for its anti-epileptic properties to treat and prevent seizures. The title compound, poly[aquatris(μ-4,4-diphenyl-2,5-dioxoimidazolidin-1-ido)trimethanoltrisodium(I)], [Na(CHNO)(CHO)(HO)], a methanol solvate and hydrate of phenytoin sodium, forms a modulated crystal structure that consists of a supercell made up of three close-to-identical repeat units. Each of the basic fragments consists of one phenytoin anion, a sodium cation, and either a methanol, or a methanol and a water molecule coordinated to the sodium ion, yielding a formula unit of Na(CHNO)(CHOH)(HO) for each of the three segments (x, y = 0 or 1; x + y = 1 or 2).

Endocytic Profiling of Cancer Cell Models Reveals Critical Factors Influencing LNP-Mediated mRNA Delivery and Protein Expression.

Lipid nanoparticles have great potential for delivering nucleic-acid-based therapeutics, but low efficiency limits their broad clinical translation. Differences in transfection capacity between in vitro models used for nanoparticle pre-clinical testing are poorly understood. To address this, using a clinically relevant lipid nanoparticle (LNP) delivering mRNA, we highlight specific endosomal characteristics in in vitro tumor models that impact protein expression.

Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant.

Importance: Patients with atrial fibrillation (AF) who use a direct oral anticoagulant (DOAC) and request elective surgery or procedure present a common clinical situation yet perioperative management is uncertain.

Objective: To investigate the safety of a standardized perioperative DOAC management strategy.

Design, Setting, And Participants: The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) cohort study conducted at 23 clinical centers in Canada, the United States, and Europe enrolled and screened patients from August 1, 2014, through July 31, 2018.

Quantifying Behavioral Sensation Seeking With the Aroma Choice Task.

Our goal was to develop a behavioral measure of sensation seeking (SS). The Aroma Choice Task (ACT) assesses preference for an intense, novel, varied, and risky (exciting) option versus a mild, safe (boring) option using real-time odorant delivery. A total of 147 healthy young adults completed 40 binary choice trials.

Dust Sources in the Salton Sea Basin: A Clear Case of an Anthropogenically Impacted Dust Budget.

The Salton Sea Basin in California suffers from poor air quality, and an expanding dry lakebed (playa) presents a new potential dust source. In 2017-18, depositing dust was collected approximately monthly at five sites in the Salton Sea Basin and analyzed for total elemental and soluble anion content. These data were analyzed with Positive Matrix Factorization (PMF).

A review of the usefulness of clinical supervisor reports when writing educational supervisor reports.

In GP training, educational supervisors are responsible for collating evidence of a trainee's performance and progress to allow them to progress to the next stage of training. In hospital posts, they rely upon a clinical supervisor's report to help assess progress. Clinical supervisors are clinicians from various specialties who may not have an in-depth knowledge of the GP training programme, and anecdotally, our impression was that clinical supervisor reports were impersonal and not helpful in assessing a trainee's performance.

Targeting Translation of mRNA as a Therapeutic Strategy in Cancer.

Purpose Of Review: To highlight recent results in targeting mRNA translation and discuss the results and prospects of translation inhibitors in cancer therapy.

Recent Findings: Until recently, inhibitors of mRNA translation have been thought to likely lack a therapeutic window. In 2012, the Food and Drug Administration (FDA) approved omacetaxine mepesuccinate (homoharringtonine) for the treatment of adults with chronic myelogenous leukemia (CML) who are resistant to at least two tyrosine kinase inhibitors.

Elevated International Normalized Ratio (INR) is Associated With an Increased Risk of Intraventricular Hemorrhage in Extremely Preterm Infants.

Introduction: The international normalized ratio (INR), a standardized method of reporting the prothrombin time, can be a surrogate marker of the vitamin K-dependent coagulation pathways.

Objective: To evaluate the relationship between INR measurements in the first 48 hours of life and subsequent development of intraventricular hemorrhage (IVH) in extremely preterm infants.

Materials And Methods: A single-center retrospective, observational cohort study of infants born at <28 weeks gestation.

Higher Prevalence of Abnormal Electrocardigrams (ECG) in African Americans Undergoing Screening ECG and Echocardiography.

Background: African American (AA) has higher prevalence of abnormal electrocardigrams (ECG) in general population. However, the degree of these abnormalities in a healthy population undergoing screening echocardiography is not known. The goal of this study was to evaluate the prevalence of ECG abnormalities reported during screening echocardiography based on race.

PD-1 Pandemonium at the American Association for Cancer Research Annual Meeting.

This editorial describes the results of discussions between the U.S. FDA Oncology Center of Excellence and members of six pharmaceutical companies—a forum aptly named PD‐1 Pandemonium—regarding development and regulatory approvals of immune checkpoint inhibitors.

Publish or Perish v2.

Communication of clinical trial outcomes is important, but the results of many clinical trials are never published. If we do not publish the results of clinical trials, the lessons learned from those trials will perish. The Oncologist offers a powerful solution through the Clinical Trial Results publishing platform, which uses an established template for authors to easily build a manuscript by simply providing the essential trial data.

Ezh2-dCas9 and KRAB-dCas9 enable engineering of epigenetic memory in a context-dependent manner.

Background: Rewriting of the epigenome has risen as a promising alternative to gene editing for precision medicine. In nature, epigenetic silencing can result in complete attenuation of target gene expression over multiple mitotic divisions. However, persistent repression has been difficult to achieve in a predictable manner using targeted systems.

Extracellular vesicles induce minimal hepatotoxicity and immunogenicity.

Extracellular vesicles (EVs) mediate cellular communication through the transfer of active biomolecules, raising interest in using them as biological delivery vehicles for therapeutic drugs. For drug delivery applications, it is important to understand the intrinsic safety and toxicity liabilities of EVs. Nanoparticles, including EVs, typically demonstrate significant accumulation in the liver after systemic administration in vivo.

Delayed cord clamping with stabilisation at all preterm births - feasibility and efficacy of a low cost technique.

Objectives: Meta-analysis data suggests that Delayed cord clamping (DCC) in preterm infants is associated with a 32% reduction in mortality. Reported rates of this intervention are low, particularly for caesarean deliveries. Perceived difficulties providing respiratory support and thermal care during DCC may be barriers to implementation of this intervention.

Evaluation of Teen BodyWise: A pilot study of a body image group adapted for adolescent inpatients with anorexia nervosa.

Purpose: Body image disturbance is a key characteristic of anorexia nervosa (AN); however, research into these difficulties among adolescents with AN is limited and is yet to assess the best treatments for this population.

Methods: Fifty-two adolescents receiving inpatient treatment for AN attended Teen BodyWise, an eight-session body image group adapted for adolescents. Measures assessing shape and weight concerns, ability to discuss body image, sociocultural attitudes, body avoidance, body checking, and motivation were given before and after the group, and participant feedback was elicited.

Unexpected term NICU admissions: a marker of obstetrical care quality?

Background: Unexpected admissions of term neonates to the neonatal intensive care unit and unexpected postnatal complications have been proposed as neonatal-focused quality metrics for intrapartum care. Previous studies have noted significant variation in overall hospital neonatal intensive care unit admission rates; however, little is known about the influence of obstetric practices on these rates or whether variation among unanticipated admissions in low-risk, term neonates can be attributed to systemic hospital practices.

Objective: The objective of the study was to examine the relative effects of patient characteristics and intrapartum events on unexpected neonatal intensive care unit admissions and to quantify the between-hospital variation in neonatal intensive care unit admission rates among this group of neonates.

An audit of propofol administration in the intensive care unit: Infusion pump-recorded versus electronically documented amounts.

Background: Although propofol is widely used for sedation in intensive care units around Australia, evaluation of bedside nursing practices of the administration of propofol have been limited. We investigated whether there was a discrepancy between the amount of propofol delivered by the infusion pump and that recorded electronically and consequently patient exposure to avoidable harms.

Aims: The aim of this research was to compare the total amount of propofol administered to intensive care patients via a programmable infusion pump with that documented in the electronic medical record (EMR).

Adjuvant and neoadjuvant cancer therapies: A historical review and a rational approach to understand outcomes.

Drug development in oncology usually establishes efficacy in metastatic disease before advancing a therapy to the adjuvant or neoadjuvant settings. Unfortunately, too often use in adjuvant or neoadjuvant settings fails to improve overall survival. Reasons for the modest benefits include the fact that in many cases surgery cures a majority of patients making it difficult to demonstrate gains.

rMyCoPortal - an R package to interface with the Mycology Collections Portal.

The understanding of the biodiversity and biogeographical distribution of fungi is still limited. The small number of online databases and the large effort required to access existing data have prevented their use in research articles. The Mycology Collections Portal was established in 2012 to help alleviate these issues and currently serves data online for over 4.

Neoadjuvant Treatment for Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited effective therapeutic options and exceedingly high mortality rates. Currently, cure can only be achieved through resection, however the vast majority of patients present with advanced disease for which upfront surgery is not an option. In an effort to improve surgical candidacy, neoadjuvant chemotherapy, with or without radiation therapy, is often used in an effort to downstage borderline resectable and locally advanced tumors, and some argue for its use even in patients with resectable tumors.

Absence of biomarker evidence for early eukaryotic life from the Mesoproterozoic Roper Group: Searching across a marine redox gradient in mid-Proterozoic habitability.

By about 2.0 billion years ago (Ga), there is evidence for a period best known for its extended, apparent geochemical stability expressed famously in the carbonate-carbon isotope data. Despite the first appearance and early innovation among eukaryotic organisms, this period is also known for a rarity of eukaryotic fossils and an absence of organic biomarker fingerprints for those organisms, suggesting low diversity and relatively small populations compared to the Neoproterozoic era.

New Insights on Solid-State Changes in the Levothyroxine Sodium Pentahydrate during Dehydration and its Relationship to Chemical Instability.

Levothyroxine sodium pentahydrate (LEVO) tablets have been on the US market since the mid-twentieth century and remain the most highly prescribed product. Unfortunately, levothyroxine sodium tablets have also been one of the most highly recalled products due to potency and dissolution failures on stability. In 2008, the assay limits were tightened, yet the recalls did not decline, which highlights the serious quality concerns remaining to be elucidated.

Targeting mitochondrial hexokinases increases efficacy of histone deacetylase inhibitors in solid tumor models.

Hexokinase 1 and 2 have been shown to inhibit Bak- and Bax-mediated apoptosis, leading us to combine the histone deacetylase inhibitor romidepsin with clotrimazole or bifonazole, two compounds that reportedly decrease mitochondrial localization of hexokinases. Cancer cell lines derived from breast, kidney, lung, colon or ovarian cancers were treated with a short-term exposure to 25 ng/ml romidepsin combined with either clotrimazole or bifonazole. The combination of romidepsin with 25 µM clotrimazole or bifonazole resulted in increased annexin staining compared to cells treated with any of the drugs alone.

American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy.

Background: Venous thromboembolism (VTE) complicates ∼1.2 of every 1000 deliveries. Despite these low absolute risks, pregnancy-associated VTE is a leading cause of maternal morbidity and mortality.

American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism.

Background: Modern diagnostic strategies for venous thromboembolism (VTE) incorporate pretest probability (PTP; prevalence) assessment. The ability of diagnostic tests to correctly identify or exclude VTE is influenced by VTE prevalence and test accuracy characteristics.

Objective: These evidence-based guidelines are intended to support patients, clinicians, and health care professionals in VTE diagnosis.