Organic impurity profiling of fentanyl samples associated with recent clandestine laboratory methods.

Nearly a decade ago, fentanyl reappeared in the United States illicit drug market. In the years since, overdose deaths have continued to rise as well as the amount of fentanyl seized by law enforcement agencies. Research surrounding fentanyl production has been beneficial to regulatory actions and understanding illicit fentanyl production.

A Survey of Dentist Anesthesiologists on Preoperative Intramuscular Sedation.

Objective: The induction of general anesthesia for children and patients with special needs frequently requires preinduction sedation, especially when anxiety and agitation lead to violent or combative behavior. In these situations, preoperative intramuscular (IM) sedation may facilitate patient transfer, intravenous cannulation, and/or mask induction. This survey aimed to capture data regarding the current preoperative IM sedation practices of dentist anesthesiologists.

Kawasaki Disease and General Anesthesia for Dental Treatment: A Case Report.

Kawasaki disease (KD) is an acute vasculitis of childhood and is the leading cause of acquired heart disease in children in developed countries. Failure to quickly diagnose and treat patients with KD can result in severe cardiac sequelae, especially coronary artery aneurysms (CAAs). Patients with a prior diagnosis of KD who require general anesthesia (GA) may present unique challenges depending on the severity of any cardiovascular sequelae.

Bacterial protease activity as a biomarker to assess the risk of non-healing in chronic wounds: Results from a multicentre randomised controlled clinical trial.

Millions worldwide suffer from chronic wounds challenging clinicians and burdening healthcare systems. Bacteria impede wound healing; however, the diagnosis of excessive bacterial burden or infection is elusive. Clinical signs and symptoms of infection are inaccurate and unreliable.

Patients with psychiatric disease: implications for anesthesiologists.

Purpose Of Review: Psychiatric illness is common in patients presenting for surgery. Overall health and surgical outcomes are adversely affected by the presence of psychiatric comorbidities.

Recent Findings: As new treatment modalities become available, their perioperative implications need to be evaluated.

Retrospective Comparison of Intramuscular Admixtures of Ketamine and Dexmedetomidine Versus Ketamine and Midazolam for Preoperative Sedation.

Precooperative children and patients with intellectual disabilities often require intramuscular (IM) sedation prior to the induction of general anesthesia (GA). Ketamine is an effective preinduction sedative but can produce significant adverse side effects. Dexmedetomidine, a sedative with sympatholytic and analgesic properties, may provide advantages when used in combination with ketamine.

Tracheopulmonary Complications of a Malpositioned Nasogastric Tube.

Tracheopulmonary complications following placement of a nasogastric (NG) feeding tube are uncommon but can cause significant morbidity and mortality. In this case report, an 83-year-old woman of American Society of Anesthesiologists class IV with underlying pulmonary disease required placement of an NG feeding tube after surgical treatment of primary squamous cell carcinoma of the tongue. Malpositioning of the NG feeding tube into the right pleural space was confirmed by computed tomography.

Gender differences in college student physical activity, and campus recreational facility use, and comfort.

To examine disparities in physical activity, campus recreation facility (CRF) use, and CRF comfort of college students. Students ( = 319) responded to an online survey that assessed their demographics, physical activity behaviors, CRF use, comfort using CRFs, as well as reasons for discomfort, and strategies used to feel comfortable. Women reported less muscle-strengthening activity, lower frequency of weight use and informal sport participation, and higher frequency of cardio and group exercise participation.

ATI-2173, a Novel Liver-Targeted Non-Chain-Terminating Nucleotide for Hepatitis B Virus Cure Regimens.

ATI-2173 is a novel liver-targeted molecule designed to deliver the 5'-monophosphate of clevudine for the treatment of chronic hepatitis B infection. Unlike other nucleos(t)ides, the active clevudine-5'-triphosphate is a noncompetitive, non-chain-terminating inhibitor of hepatitis B virus (HBV) polymerase that delivers prolonged reduction of viremia in both a woodchuck HBV model and in humans for up to 6 months after cessation of treatment. However, long-term clevudine treatment was found to exhibit reversible skeletal myopathy in a small subset of patients and was subsequently discontinued from development.

Analysis of the Potential for -Hydroxycytidine To Inhibit Mitochondrial Replication and Function.

-Hydroxycytidine (NHC) is an antiviral ribonucleoside analog that acts as a competitive alternative substrate for virally encoded RNA-dependent RNA polymerases. It exhibits measurable levels of cytotoxicity, with 50% cytotoxic concentration values ranging from 7.5 μM in CEM cells and up to >100 μM in other cell lines.

The prophylactic and therapeutic activity of a broadly active ribonucleoside analog in a murine model of intranasal venezuelan equine encephalitis virus infection.

The New World alphaviruses Venezuelan, Eastern, and Western equine encephalitis viruses (VEEV, EEEV and WEEV, respectively) commonly cause a febrile disease that can progress to meningoencephalitis, resulting in significant morbidity and mortality. To address the need for a therapeutic agent for the treatment of Alphavirus infections, we identified and pursued preclinical characterization of a ribonucleoside analog EIDD-1931 (β-D-N-hydroxycytidine, NHC), which has shown broad activity against alphaviruses in vitro and has a very high genetic barrier for development of resistance. To be truly effective as a therapeutic agent for VEEV infection a drug must penetrate the blood brain barrier and arrest virus replication in the brain.

Development of a novel progesterone analog in the treatment of traumatic brain injury.

Although systemic progesterone (PROG) treatment has been shown to be neuroprotective by many laboratories and in multiple animal models of brain injury including traumatic brain injury (TBI), PROG's poor aqueous solubility limits its potential for use as a therapeutic agent. The problem of solubility presents challenges for an acute intervention for neural injury, when getting a neuroprotectant to the brain quickly is crucial. Native PROG (nPROG) is hydrophobic and does not readily dissolve in an aqueous-based medium, so this makes it harder to give under emergency field conditions.

β-d--Hydroxycytidine Is a Potent Anti-alphavirus Compound That Induces a High Level of Mutations in the Viral Genome.

Venezuelan equine encephalitis virus (VEEV) is a representative member of the New World alphaviruses. It is transmitted by mosquito vectors and causes highly debilitating disease in humans, equids, and other vertebrate hosts. Despite a continuous public health threat, very few compounds with anti-VEEV activity in cell culture and in mouse models have been identified to date, and rapid development of virus resistance to some of them has been recorded.

Evaluating the neurotherapeutic potential of a water-soluble progesterone analog after traumatic brain injury in rats.

The poor aqueous solubility of progesterone (PROG) limits its potential use as a therapeutic agent. We designed and tested EIDD-1723, a novel water-soluble analog of PROG with >100-fold higher solubility than that of native PROG, as candidate for development as a field-ready treatment for traumatic brain injury (TBI). The pharmacokinetic effects of EIDD-1723 on morphological and functional outcomes in rats with bilateral cortical impact injury were evaluated.

Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial.

Purpose: To assess the effects of adjuvant hormone therapy (AHT) on survival and disease outcome in women with epithelial ovarian cancer.

Patients And Methods: Participants were premenopausal and postmenopausal women who had been diagnosed with epithelial ovarian cancer (any International Federation of Gynecology and Obstetrics stage) 9 or fewer months previously. Ineligible patients included those with deliberately preserved ovarian function, with a history of a hormone-dependent malignancy, or with any contraindications to hormone-replacement therapy.

Improved sperm cryosurvival in diluents containing amides versus glycerol in the Przewalski's horse (Equus ferus przewalskii).

Two studies were conducted to understand sperm cryosensitivity in an endangered equid, the Przewalski's horse (Equus ferus przewalski), while testing the cryoprotectant ability of formamides. The first assessed the toxicity of permeating cryoprotectants (glycerol, methylformamide [MF] and dimethylformamide [DMF]) to Przewalski's horse spermatozoa during liquid storage at 4°C. The second examined the comparative influence of three diluents (with or without formamides) on cryosurvival of sperm from the Przewalski's versus domestic horse.

Water-soluble progesterone analogues are effective, injectable treatments in animal models of traumatic brain injury.

After more than 30 years of research and 30 failed clinical trials with as many different treatments, progesterone is the first agent to demonstrate robust clinical efficacy as a treatment for traumatic brain injuries. It is currently being investigated in two, independent phase III clinical trials in hospital settings; however, it presents a formidable solubility challenge that has so far prevented the identification of a formulation that would be suitable for emergency field response use or battlefield situations. Accordingly, we have designed and tested a novel series of water-soluble analogues that address this critical need.

Preoperative incisional and intraoperative frozen section biopsy techniques have comparable accuracy in the diagnosis of benign intraosseous jaw pathology.

Purpose: To compare the accuracy of intraoperative frozen section (FS) and preoperative incisional biopsy (IB) techniques to diagnose benign intraosseous jaw lesions.

Materials And Methods: This is a retrospective cohort study composed of subjects with benign intraosseous jaw lesions. The predictor variable was the technique for establishing a preliminary diagnosis of the lesion, preoperative IB or intraoperative FS.

Radical and Heck cyclizations of diastereomeric o-haloanilide atropisomers.

The outcomes of radical cyclizations and Heck reactions of N-(cyclohex-2-enyl)-N-(2-iodophenyl)acetamides depend critically on the configurations of the chiral axis and the stereocenter. In substrates without an ortho-methyl group, the diastereomeric precursors interconvert slowly at ambient temperatures. Cyclization of enriched mixtures of diastereomers provided similar yields of acetyl tetrahydrocarbazoles or dihydrocarbazoles, suggesting that interconversion of the radical or organometallic intermediates also occurs.

Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial.

Background: Serum CA125 concentration often rises several months before clinical or symptomatic relapse in women with ovarian cancer. In the MRC OV05/EORTC 55955 collaborative trial, we aimed to establish the benefits of early treatment on the basis of increased CA125 concentrations compared with delayed treatment on the basis of clinical recurrence.

Methods: Women with ovarian cancer in complete remission after first-line platinum-based chemotherapy and a normal CA125 concentration were registered for this randomised controlled trial.

Memory of axial chirality in aryl radical phosphanylations.

The rate constant for phosphanylation of an aryl radical with trimethylstannyl diphenylphosphane (Me(3)SnPPh(2)) has been measured as k(phos) approximately 9 x 10(8) M(-1) s(-1). Aryl radicals derived from several axially chiral o-haloanilides are trapped by Me(3)SnPPh(2) with complete retention of axial chirality as shown by oxidation of the phosphanes to give stable, easily analyzed phosphane oxides or sulfides. Double phosphanylations of o,o'-dihaloanilides followed by treatment with H(2)O(2) or S(8) in either order give enantiomers of a mixed diphosphane oxide sulfide.

The effect of intrauterine growth retardation on the expression of developmental factors in porcine placenta subsequent to the initiation of placentation.

Intrauterine growth retardation (IUGR) hinders fetal growth and postnatal development in swine; however the etiology of IUGR is essentially unknown. Expression of fourteen candidate genes associated with placental development or IUGR was examined in gestational day 50 (gd50) control and IUGR fetus whole placental tissue or areolae by real-time PCR. Endothelial nitric oxide synthase (ENOS) mRNA expression was elevated in gd50 IUGR placenta and areola compared to gd50 control.

Using fluorescence-activated flow cytometry to determine reactive oxygen species formation and membrane lipid peroxidation in viable boar spermatozoa.

Fluorescence-activated flow cytometry analyses were developed for determination of reactive oxygen species (ROS) formation and membrane lipid peroxidation in live spermatozoa loaded with, respectively, hydroethidine (HE) or the lipophilic probe 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid, C(11)BODIPY(581/591) (BODIPY). ROS was detected by red fluorescence emission from oxidization of HE and membrane lipid peroxidation was detected by green fluorescence emission from oxidation of BODIPY in individual live sperm. Of the reactive oxygen species generators tested, BODIPY oxidation was specific for FeSo4/ascorbate (FeAc), because menadione and H(2)O(2) had little or no effect.

The impact of new dental schools on the dental workforce through 2022.

Following a wave of dental school closures from 1986 to 2001 and a perceived shortage of dentists, three new dental schools were established between 1997 and 2003, and eight more are in various stages of planning and development to open over the next decade. Conditions are moving rapidly, and several institutions have stated intentions to open new dental schools since this analysis. This article presents a supply-side analysis of the impact of the new schools on the effective dentist to population ratio, taking into account changes in graduation rates, retirement rate, population growth, productivity, and gender ratio of the profession.