Drug-Drug Interaction Potential of Mavacamten with Midazolam: Combined Results from Clinical and Model-Based Studies.

Mavacamten is a potential inducer of cytochrome P450 (CYP) 3A4 and could reduce the effectiveness of concomitant drugs that are metabolized by CYP3A4, such as midazolam. This study aimed to determine if repeat doses of mavacamten achieving clinically relevant exposures affected midazolam exposure. This was a single-center, open-label study in healthy participants.

A Multicenter Home-based Prehabilitation Intervention in Kidney Transplant Candidates.

Background: Frailty is a modifiable risk factor for morbidity and mortality among kidney transplant (KT) candidates. We previously demonstrated that an 8-wk center-based exercise intervention is associated with improved frailty parameters in patients with advanced chronic kidney disease. This study aimed to adapt the intervention for home-based delivery and examine its feasibility, safety, and acceptability in a multicenter cohort of KT candidates.

Absolute oral bioavailability of milvexian spray-dried dispersion formulation under fasted and fed conditions in healthy adult participants: An intravenous microtracer approach.

Milvexian is an oral, small-molecule factor XIa inhibitor being developed to prevent thromboembolic events. This study assessed the absolute bioavailability (F) of milvexian following single doses of milvexian spray-dried dispersion (SDD) formulation under fed and fasted conditions, and milvexian solution, in healthy adult participants using an intravenous microtracer approach. This was a phase I, open-label, partially randomized, 4-sequence, 5-period crossover study.

First-in-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of BMS-986308: A Renal Outer Medullary Potassium Channel Inhibitor.

In patients with heart failure (HF) who respond inadequately to loop diuretic therapy, BMS-986308, an oral, selective, reversible renal outer medullary potassium channel (ROMK) inhibitor may represent an effective diuretic with a novel mechanism of action. We present data from the first-in-human study aimed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) following single ascending doses of BMS-986308 in healthy adult participants. Forty healthy participants, aged from 20 to 55 years, and body mass index (BMI) from 19.

A Comparative Study Between Intravenous Esmolol and Oral Clonidine in Attenuating Hyperdynamic Cardiovascular Response to Laryngoscopy and Endotracheal Intubation.

Background In today's era of anesthesia, balanced anesthesia is the main basis of patient care and pain management. Of all the medications given during general anesthesia, premedication, induction agents, and muscle relaxants play a major role in keeping the hemodynamics properly under control. When laryngoscopy is performed to intubate, a pain stimulus will be generated, leading to a rise in blood pressure and heart rate.

Safety, tolerability, pharmacokinetics and pharmacodynamics of milvexian with aspirin and/or clopidogrel in healthy participants.

Milvexian, an oral activated Factor XI (FXIa) inhibitor, is in clinical studies where it may be combined with antiplatelet agents, including aspirin and/or clopidogrel, to prevent thromboembolic diseases. This phase I trial assessed safety, pharmacokinetics, and pharmacodynamics of milvexian coadministration with aspirin and/or clopidogrel in healthy participants through 3 drug-drug interaction studies using a 3-period, 3-treatment, crossover design. A total of 113 participants were randomized to receive milvexian (200 mg; twice daily for 5 days) or matched placebo coadministered with once-daily aspirin (325 mg for 5 days) and/or clopidogrel (Day 1: 300 mg; Days 2-5: 75 mg).

Effect of Activated Charcoal on Mavacamten Pharmacokinetics in Healthy Participants.

Objective: To assess the effect of activated charcoal on the single-dose pharmacokinetics of mavacamten when administered 2 h or 6 h after mavacamten dosing.

Methods: In this open-label, randomized, parallel-group study, healthy adults were randomized into three groups to receive mavacamten 15 mg alone or mavacamten 15 mg plus activated charcoal 50 g administered either 2 h or 6 h after mavacamten dosing. Pharmacokinetic parameters were derived from plasma concentration-time data using noncompartmental methods.

Atmospheric gaseous mercury and associated health risk assessment in the economic capital of India.

Mercury cycling in coastal metropolitan areas on the west coast of India becomes complex due to the combined effects of both intensive domestic anthropogenic emissions and marine air masses. The present study is based on yearlong data of continuous measurements of gaseous elemental mercury (GEM) concentration concurrent with meteorological parameters and some air pollutants at a coastal urban site in Mumbai, on the west coast of India, for the first time. The concentration of GEM was found in a range between 2.

Implicit neural representations in light microscopy.

Three-dimensional stacks acquired with confocal or two-photon microscopy are crucial for studying neuroanatomy. However, high-resolution image stacks acquired at multiple depths are time-consuming and susceptible to photobleaching. In vivo microscopy is further prone to motion artifacts.

Model-Based Dose Selection of Subcutaneous Nivolumab in Patients with Advanced Solid Tumors.

The pharmacokinetics (PK) of intravenous (i.v.) nivolumab is well characterized.

Monitoring and reporting the US COVID-19 vaccination effort.

Immunizations are an important tool to reduce the burden of vaccine preventable diseases and improve population health. High-quality immunization data is essential to inform clinical and public health interventions and respond to outbreaks of vaccine-preventable diseases. To track COVID-19 vaccines and vaccinations, CDC established an integrated network that included vaccination provider systems, health information exchange systems, immunization information systems, pharmacy and dialysis systems, vaccine ordering systems, electronic health records, and tools to support mass vaccination clinics.

Pharmacokinetics and Safety of the Tyrosine Kinase 2 Inhibitor Deucravacitinib in Healthy Chinese Subjects.

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, blocks cytokine signaling involved in psoriasis pathogenesis. This ethnic-bridging study evaluated deucravacitinib pharmacokinetics, tolerability, and safety in healthy Chinese subjects.

Methods: This phase I, double-blind, single-/multiple-dose study randomized healthy Chinese subjects 4:1 to a single dose of deucravacitinib 6 mg or placebo (group 1) or deucravacitinib 12 mg or placebo (group 2) on day 1; groups 1 and 2 received deucravacitinib 6 mg and 12 mg once daily, respectively, or placebo on days 5-19.

Absolute and Relative Bioavailability of Oral Solid Dosage Formulations of Deucravacitinib in Humans.

Deucravacitinib is an oral, selective, allosteric inhibitor of tyrosine kinase 2, an intracellular signaling kinase involved in the pathogenesis of immune-mediated inflammatory diseases. The absolute and relative bioavailability (BA) were evaluated in phase 1, open-label studies in healthy adults to assess (1) the absolute BA of the deucravacitinib tablet formulation following single oral administration of a 12-mg tablet and an intravenous microdose infusion of 0.1-mg carbon-13 and nitrogen-15-labeled deucravacitinib ([ C , N ] deucravacitinib) solution in 8 subjects, and (2) the relative oral BA of deucravacitinib tablet and capsule formulations at the 3- and 12-mg dose levels in 20 subjects.

Impact of Bonding Temperature on Microstructure, Mechanical, and Fracture Behaviors of TLP Bonded Joints of Al2219 with a Cu Interlayer.

The present study aims at producing transient liquid phase (TLP) bonded Al2219 joints with pure Cu (copper) as an interlayer. The TLP bonding is carried out at the bonding temperatures in the range of 480 to 520 °C while keeping the bonding pressure (2 MPa) and time (30 min.) constant.

Characterization of fine particulate matter water-soluble inorganic ions and estimation of aerosol acidity at three COALESCE network sites - Mysuru, Bhopal, and Mesra - in India.

The study was carried out to understand the chemical, spatiotemporal characteristics of water-soluble inorganic ions (WSIIs), their association with PM mass, and aerosol acidity in three COALESCE (carbonaceous aerosol emissions, source apportionment, and climate impacts) network sites of India (Mesra - Eastern India, Bhopal - Central India and Mysuru - Southern India). Alternate-day 24-h integrated bulk PM samples were collected during 2019 along with on-site meteorological parameters. Annual average PM concentrations were 67 ± 46 µg m, 54 ± 47 µg m, and 30 ± 24 µg m at Mesra, Bhopal, and Mysuru, respectively.

Al2014-Alumina Aerospace Composites: Particle Size Impacts on Microstructure, Mechanical, Fractography, and Wear Characteristics.

An Al2014-alumina (AlO) composite's characteristics are significantly influenced by the reinforcement particle size variation. Therefore, this study examines the microstructure, mechanical, fractography, and wear performance of an Al2014-AlO composite made using a unique two-stage stir casting method and various alumina weight fractions (9, 12, and 15 wt %). Three categories of alumina particle size are used, i.

Evaluation of safety, pharmacokinetics, and pharmacodynamics of apixaban in pediatric subjects at risk of venous or arterial thrombotic disorder.

Apixaban is an oral small-molecule, direct factor Xa (FXa) inhibitor approved in adults for treatment of deep vein thrombosis and pulmonary embolism, and for reducing risk of venous thromboembolism recurrence after initial anticoagulant therapy. This phase I study (NCT01707394) evaluated the pharmacokinetics (PKs), pharmacodynamics (PDs), and safety of apixaban in pediatric subjects (<18 years), enrolled by age group, at risk of venous or arterial thrombotic disorder. A single apixaban dose, targeting adult steady-state exposure with apixaban 2.

COVID-19 Vaccination Coverage and Demographic Characteristics of Infants and Children Aged 6 Months-4 Years - United States, June 20-December 31, 2022.

Although severe COVID-19 illness and hospitalization are more common among older adults, children can also be affected (1). More than 3 million cases of COVID-19 had been reported among infants and children aged <5 years (children) as of December 2, 2022 (2). One in four children hospitalized with COVID-19 required intensive care; 21.

Arc-driven mGRASP highlights CA1 to CA3 synaptic engrams.

Subpopulations of neurons display increased activity during memory encoding and manipulating the activity of these neurons can induce artificial formation or erasure of memories. Thus, these neurons are thought to be cellular engrams. Moreover, correlated activity between pre- and postsynaptic engram neurons is thought to lead to strengthening of their synaptic connections, thus increasing the probability of neural activity patterns occurring during encoding to reoccur at recall.

Impact assessment of surface ozone exposure on crop yields at three tropical stations over India.

Surface ozone is a damaging pollutant for crops and ecosystems, and the ozone-induced crop losses over India remain uncertain and a topic of debate due to a lack of sufficient observations and uncertainties involved in the modeled results. In this study, we have used the observational data from MAPAN (Modelling Air Pollution And Networking) for the first time to estimate the relative yield losses, crop production losses, and economic losses for the two major crops (wheat and rice). The detailed estimation has been done focusing on three individual suburban sites over India (Patiala, Tezpur, and Delhi) and compared with other related studies over the Indian region.

Effects of rifampin on the pharmacokinetics and pharmacodynamics of milvexian, a potent, selective, oral small molecule factor XIa inhibitor.

Milvexian (BMS-986177/JNJ-70033093) is a potent, oral small molecule that inhibits the active form of factor XI with high affinity and selectivity. This study assessed the single-dose pharmacokinetic and pharmacodynamic properties of milvexian co-administered with rifampin, an organic anion transport protein (OATP) inhibitor and potent cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp) inducer. In this open-label, nonrandomized, single-sequence study, healthy participants (N = 16) received single doses of milvexian on Day 1 (100 mg), milvexian and rifampin (600 mg) on Day 4, rifampin on Days 5-11, milvexian and rifampin on Day 12, and rifampin on Days 13-14.

Sociodemographic Variation in Early Uptake of COVID-19 Vaccine and Parental Intent and Attitudes Toward Vaccination of Children Aged 6 Months-4 Years - United States, July 1-29, 2022.

COVID-19 vaccines are safe and effective for infants and young children, and on June 18, 2022, CDC recommended COVID-19 vaccination for infants and children (children) aged 6 months-4 years (1,2). As of November 9, 2022, based on administrative data reported to CDC,* 5.9% of children aged <2 years and 8.

First-in-human study of deucravacitinib: A selective, potent, allosteric small-molecule inhibitor of tyrosine kinase 2.

This randomized, double-blind, single- and multiple-ascending dose study assessed the pharmacokinetics (PKs), pharmacodynamics, and safety of deucravacitinib (Sotyktu™), a selective and potent small-molecule inhibitor of tyrosine kinase 2, in 100 (75 active, 25 placebo) healthy volunteers (NCT02534636). Deucravacitinib was rapidly absorbed, with a half-life of 8-15 h, and 1.4-1.

Celebrating 25 Years of Varicella Vaccination Coverage for Children and Adolescents in the United States: A Success Story.

Tracking vaccination coverage is a critical component of monitoring a vaccine program. Three different surveillance systems were used to examine trends in varicella vaccination coverage during the United States vaccination program: National Immunization Survey-Child, National Immunization Survey-Teen, and immunization information systems (IISs). The relationship of these trends to school requirements and disease decline was also examined.

Using a Cloud-Based Machine Learning Classification Tree Analysis to Understand the Demographic Characteristics Associated With COVID-19 Booster Vaccination Among Adults in the United States.

A tree model identified adults age ≤34 years, Johnson & Johnson primary series recipients, people from racial/ethnic minority groups, residents of nonlarge metro areas, and those living in socially vulnerable communities in the South as less likely to be boosted. These findings can guide clinical/public health outreach toward specific subpopulations.