The massic activity of Ac in 0.1 mol/L HCl was measured by multiple primary methods over four consistent measurement campaigns. Results from the triple-to-double coincidence ratio (TDCR) method of liquid scintillation (LS) counting were in accord with other LS-based primary methods.
View Article and Find Full Text PDFBackground: The microbial testing platform, Peel Plate™, was developed with Baird Parker ingredients for Staphylococcus aureus (SA) specificity. After rehydrating with 1 mL of the diluted food sample, Peel Plate SA is incubated for 24-48 h at 35-37 °C and observed for purple colonies.
Objective: A validation study was performed to evaluate Peel Plate SA for enumeration of S.
Objectives: Long cardiopulmonary bypass times are associated with adverse postoperative outcomes and increased healthcare resource use. It is likely that this effect is pronounced in smaller patients. Previous studies have been criticized for not taking into consideration that prolonged bypass times are often due to higher complexity.
View Article and Find Full Text PDFAnimal movement plays a key role in many ecological processes and has a direct influence on an individual's fitness at several scales of analysis (i.e., next-step, subdiel, day-by-day, seasonal).
View Article and Find Full Text PDFCarbon-14 labeling synthesis of RORγt inhibitor JNJ-61803534 (1) was accomplished in four steps with the C14 label located at the thiazole-2-carboxamide carbon. The synthesis featured a highly efficient conversion of nitrile [C]-12 to ester [C]-17 under mild conditions via an imidate intermediate, overcoming the unsuccessful direct hydrolysis of nitrile 12 under either acidic or basic conditions. Since carbon-14 labeling via [C]-nitrile installation and subsequent conversion to [C]-carboxylic acid derivatives is a common labeling strategy, an efficient conversion of a nitrile to an ester under mild conditions could be of use for the future C14 labeling syntheses.
View Article and Find Full Text PDFWe report the combination of organo-photocatalysis with transition metal (TM) catalysis for directed -hydroxylation of substituted anilides for the synthesis of α-aminophenol derivatives under mild conditions. The developed metallaphotocatalysis utilizes -pivaloyl as a directing group and phenyl iodine(III) bis(trifluoroacetate) (PIFA) in the combination of the 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) photocatalyst and [RuCl(-cymene)] TM catalyst under visible-light irradiation at room temperature. The hydroxylation reaction works well for a wide range of substrates containing electron-withdrawing substituents and could be applied to late-stage functionalization and -hydroxyl metabolite generation for drug compounds-containing anilides with electron-withdrawing substituents in a single mild reaction.
View Article and Find Full Text PDFThe human hepatocyte suspension model has been a valuable tool to study covalent binding (CVB) for compounds that form reactive metabolites. However, accurately measuring CVB values with the suspension model becomes challenging for metabolically low turnover compounds. In this study, we evaluated the HμREL human hepatocyte coculture model relative to existing literature using human hepatocyte suspension for drugs of known drug-induced liver injury category.
View Article and Find Full Text PDFBackground: Decreasing healthcare disparities in marginalized communities requires healthcare providers who understand and appreciate social, economic, and cultural backgrounds. This includes care and education focused on individuals who identify as lesbian, gay, bisexual, transgender, or queer (LGBTQ).
Methods: This study examined dental students' and residents' self-reported clinical preparedness, prejudicial attitudes (implicit and explicit), and knowledge of health disparities that exist in the LGBTQ community using the Lesbian, Gay, Bisexual, Transgender Development of Clinical Skills Scale (LGBT-DOCSS) prior to and after the presentation of an LGBTQ competency course.
Background: Burnout is a condition characterized by emotional exhaustion, low personal accomplishment, and feelings of depersonalization that may evolve as a result of chronic occupational stress. Our goal for the study was to measure the degree of burnout among US dental school faculty with less than 10 years in academia.
Materials And Methods: A mixed method approach to data collection was utilized for the study and included: A.
Dairy calves are social creatures who are highly motivated for access to a companion. Additionally, heat stress negatively affects the welfare and productivity of calves housed in outdoor hutches. However, no studies have examined the potential tradeoffs pair-housed calves face between competing motivations for social contact and thermal comfort.
View Article and Find Full Text PDFCold stress negatively affects the welfare of calves in outdoor hutches. No studies have examined the potential benefits of pair housing calves to buffer against cold stress. Our study evaluated the effects of pair versus individual housing on thermoregulatory, behavioral, and growth performance responses of calves in outdoor hutches during a Wisconsin continental winter.
View Article and Find Full Text PDFBackground: Intensive care settings have high rates of medication administration errors. Medications are often administered by nurses and midwives using a specified process (the '5 rights'). Understanding where medication errors occur, the contributing factors and how best practice is delivered may assist in developing interventions to improve medication safety.
View Article and Find Full Text PDFOral nodular chronic hyperplastic candidiasis (CHC) is a rare subset of oral CHC, a relatively uncommon condition associated with immunosuppression. We present a case of a 73-year-old female with nodular CHC of the tongue and a medical history noted for type 2 diabetes. Additionally, we discuss the diagnosis, management, and conditions potentially associated with oral nodular CHC.
View Article and Find Full Text PDFRegul Toxicol Pharmacol
March 2023
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.
View Article and Find Full Text PDFIbrutinib is an oral medication for the treatment of B cell malignancies. During its clinical development, a stable isotopologue of ibrutinib was required for the assessment of the drug's absolute oral bioavailability via intravenous microdosing. The following work describes a 10-step, gram-scale production of carbon-13 labeled ibrutinib from [ C ]phenol ( C , 99%) in 31% overall yield with >99% chemical purity and >99% enantiomeric excess (ee), suitable for intravenous microdosing in humans.
View Article and Find Full Text PDFWe investigated the initial outbreak rates and subsequent social distancing behaviour over the initial phase of the COVID-19 pandemic across 29 Combined Statistical Areas (CSAs) of the United States. We used the Numerus Model Builder Data and Simulation Analysis (NMB-DASA) web application to fit the exponential phase of a SCLAIV+D (Susceptible, Contact, Latent, Asymptomatic infectious, symptomatic Infectious, Vaccinated, Dead) disease classes model to outbreaks, thereby allowing us to obtain an estimate of the basic reproductive number R for each CSA. Values of R ranged from 1.
View Article and Find Full Text PDFBackground: An understanding of epidemiological dynamics, once confined to mathematical epidemiologists and applied mathematicians, can be disseminated to a non-mathematical community of health care professionals and applied biologists through simple-to-use simulation applications. We used Numerus Model Builder RAMP (Runtime Alterable Model Platform) technology, to construct deterministic and stochastic versions of compartmental SIR (Susceptible, Infectious, Recovered with immunity) models as simple-to-use, freely available, epidemic simulation application programs.
Results: We take the reader through simulations used to demonstrate the following concepts: 1) disease prevalence curves of unmitigated outbreaks have a single peak and result in epidemics that 'burn' through the population to become extinguished when the proportion of the susceptible population drops below a critical level; 2) if immunity in recovered individuals wanes sufficiently fast then the disease persists indefinitely as an endemic state, with possible dampening oscillations following the initial outbreak phase; 3) the steepness and initial peak of the prevalence curve are influenced by the basic reproductive value R, which must exceed 1 for an epidemic to occur; 4) the probability that a single infectious individual in a closed population (i.
Functionalized nucleosides bearing pyrimidine or purine bases can be prepared by activation of accessible pyrimidine nucleosides and subsequent transglycosylation. Nitration of lumicitabine, a 2'-fluoro-2'-deoxycytidine class antiviral agent, and its 2'-fluoro-2'-deoxyuridine precursor produce the same 5-nitro-2'-fluoro-2'-deoxyuridine. Under Vorbrüggen conditions, 5-nitrouracil serves as the leaving nucleobase and enables exchange with pyrimidine and purine nucleobases to anomeric 2'-fluoro-2'-deoxyribonucleosides in favor of β-anomers generally.
View Article and Find Full Text PDFSynthesis of multiple deuterium-labeled CCR2 antagonist JNJ-26131300, that is, [4-(1H-indol-3-yl)-piperidin-1-yl]-{1-[3-(3,4,5-trifluoro-phenyl)-acryloyl]-piperidin-4-yl}-acetic acid, is described. First, condensation of indole-D with 4-piperidone produced 3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-D , which subsequently underwent catalytic hydrogenation to give 3-piperidin-4-yl-1H-indole-D . Next, bromo-{1-[3-(3,4,5-trifluoro-phenyl)-acryloyl]-piperidin-4-yl}-acetic acid was prepared through multiple steps from 3-(3,4,5-trifluoro-phenyl)-acrylic acid and bromo-piperidin-4-yl-acetic acid ethyl ester.
View Article and Find Full Text PDFWe present methods for building a Java Runtime-Alterable-Model Platform (RAMP) of complex dynamical systems. We illustrate our methods by building a multivariant SEIR (epidemic) RAMP. Underlying our RAMP is an individual-based model that includes adaptive contact rates, pathogen genetic drift, waning and cross-immunity.
View Article and Find Full Text PDFBackground: Injury is a leading health burden in children yet relatively little is reported about the contemporary risks they face. Current national registry data may under-represent the true burden of injury to children. We aim to analyse contemporary patterns of paediatric trauma and identify current factors putting children at risk of injury.
View Article and Find Full Text PDFObjectives: To determine whether FO of passive lung insufflation during cardiopulmonary bypass correlates with postoperative pulmonary function.
Design: A retrospective, observational study SETTING: A single-center, university-affiliated, specialist cardiothoracic center in the United Kingdom.
Participants: Adult patients presenting for nonemergency, nontransplant cardiac surgery requiring cardiopulmonary bypass without the need for deep hypothermic circulatory arrest between January 1, 2018, and December 31, 2018.
The reported method involves a novel workflow that eliminates the need for authentic reference standards for the quantitation of drug metabolites in biological samples using a single multi-isotopically labeled compound bearing both radio and stable isotopes. The resulting radio and stable bifunctionalized isotopolog (RADSTIL) of the parent drug is employed as a substrate for in vitro biotransformation to targeted RADSTILs of metabolites as calibrants. Inclusion of a radio label enables both radiometric and mass spectrometric detection.
View Article and Find Full Text PDFSARS-Cov-2 escape mutations (EM) have been detected and are spreading. Vaccines may need adjustment to respond to these or future mutations. We designed a population level model integrating both waning immunity and EM.
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