Effect of Daridorexant on the Pharmacokinetics of Midazolam, and on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Male Subjects.

Background And Objectives: Daridorexant, a dual orexin receptor antagonist was recently approved for the treatment of insomnia at doses up to 50 mg once per night. This study investigated the effect of single-dose and multiple-dose daridorexant 50 mg at steady state on the pharmacokinetics (PK) of the cytochrome P450 (CYP) 3A4-sensitive substrate midazolam, and the effect of single-dose daridorexant 50 mg on the PK and pharmacodynamics (PD) of the CYP2C9-sensitive substrate warfarin.

Methods: In this prospective, single-center, open-label, fixed-sequence, phase I, drug-drug interaction study, 18 healthy male subjects sequentially received Treatment A, B, and C in three periods.

Understanding Public Perceptions of Per- and Polyfluoroalkyl Substances: Infodemiology Study of Social Media.

Background: Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants that have received significant public attention. PFAS are a large group of human-made chemicals that have been used in industry and consumer products worldwide since the 1950s. Human exposure to PFAS is a growing public health concern.

Phase 1 study in healthy participants of the safety, pharmacokinetics, and pharmacodynamics of enpatoran (M5049), a dual antagonist of toll-like receptors 7 and 8.

This study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple oral doses of enpatoran (formerly named M5049), a new toll-like receptor (TLR) 7 and 8 dual antagonist, and the effect of food on a single dose in healthy participants. In this single phase 1, randomized (3:1), double-blind, placebo-controlled study, 96 participants received single and multiple ascending oral doses of enpatoran. Participants in single-dose cohorts received one dose of enpatoran (1, 3, 9, 25, 50, 100, or 200 mg) or placebo using a sentinel dosing strategy.

Advancing per- and polyfluoroalkyl substances (PFAS) research: an overview of ATSDR and NCEH activities and recommendations.

The National Center for Environmental Health (NCEH), part of the Centers for Disease Control and Prevention (CDC), and the Agency for Toxic Substances and Disease Registry (ATSDR) support and conduct research advancing national, state, and local public health response to per- and polyfluoroalkyl substances (PFAS). PFAS are a group of manufactured chemicals used in industry and consumer products that persist in the environment. Given the growing evidence linking PFAS with adverse health effects in humans, NCEH and ATSDR developed a public health research framework to capture the broad range of PFAS research activities being conducted and supported by the agency to determine future research priorities and identify opportunities for interagency collaboration.

LESS THAN HALF OF ACL-RECONSTRUCTED ATHLETES ARE CLEARED FOR RETURN TO PLAY BASED ON PRACTICE GUIDELINE CRITERIA: RESULTS FROM A PROSPECTIVE COHORT STUDY.

Background: A recently published Dutch practice guideline emphasizes criterion-based rehabilitation after anterior cruciate ligament reconstruction (ACLR) instead of time-based. As a consequence of this criterion-based rehabilitation, return to play is only suggested when athletes meet specific return to play (RTP) criteria.

Purpose: The goal of this prospective observational study was to analyze if physical therapists adhere to ACLR practice guideline RTP criteria for testing and return to sport decisions, and to explore whether there is a difference in adherence between physical therapists specialized in sports versus those who are not.

Flattening the Learning Curve: A Case-Based Video Orientation for a Subspeciality Residency Rotation.

Objective: To determine whether a clinically focused rotation orientation delivered through e-learning videos would be an effective method to improve residents' clinical knowledge and confidence.

Methods: A pre-post study design evaluated for change in knowledge and confidence between a control and intervention group of residents assigned to outpatient pediatric endocrinology rotations at 2 residency programs from July 2017 to March 2019. The intervention group utilized the first morning of the rotation to complete the video curriculum designed to rapidly orient residents to common clinical management tasks in outpatient pediatric endocrinology.

Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype.

Background And Purpose: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas.

Materials And Methods: Eligible preoperative MRIs from 28 patients (11 women; 22-53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists.

Assessment of right atrium volume by conventional CT or MR techniques: Which modality resembles in vivo reality?

Purpose: Right atrial volume (RAV) is a prognostic factor of the right heart function. This retrospective study evaluates the comparability of computed tomography (CT) and magnetic resonance imaging (MRI) for right atrial volumetry with conventional planimetric and diametric methods.

Material And Methods: 29 retrospectively included patients (18 male, 47±12years) underwent CT and 1.

A novel reconstruction tool (syngo DynaCT Head Clear) in the post-processing of DynaCT images to reduce artefacts and improve image quality.

Background: Latest generations of flat detector (FD) neuroangiography systems are able to obtain CT-like images of the brain parenchyma. Owing to the geometry of the C-arm system, cone beam artifacts are common and reduce image quality, especially at the periphery of the field of view. An advanced reconstruction algorithm (syngo DynaCT Head Clear) tackles these artifacts by using a modified interpolation-based 3D correction algorithm to improve image quality.

Neonatal diabetes, gallbladder agenesis, duodenal atresia, and intestinal malrotation caused by a novel homozygous mutation in RFX6.

Recently, bi-allelic mutations in the transcription factor RFX6 were described as the cause of a rare condition characterized by neonatal diabetes with pancreatic and biliary hypoplasia and duodenal/jejunal atresia. A male infant developed severe hyperglycemia (446 mg/dL) within 24 h of birth. Acute abdominal concerns by day five necessitated exploratory surgery that revealed duodenal atresia, gallbladder agenesis, annular pancreas and intestinal malrotation.

Plasma C-type natriuretic peptide forms and thyroid status in prepubertal children with acquired thyroid disease.

Objective: C-type natriuretic peptide (CNP) and thyroid hormone (TH) are essential for normal skeletal growth. Plasma CNP peptides correlate with growth velocity, but the relationship between thyroid status and CNP production is unknown. This study examined the impact of restoring normal TH levels on CNP and height velocity (HV) in children with acquired hypo- and hyperthyroidism.

A longitudinal assessment of lipids in youth with type 1 diabetes.

Background: Type 1 diabetes and dyslipidemia are known risk factors for cardiovascular disease (CVD), but the relationship between lipid levels in youth with type 1 diabetes and future CVD remains unknown.

Objective: To characterize lipid levels and CVD risk factors over time in youth with type 1 diabetes.

Subjects: The study included adolescents with type 1 diabetes (12-25 yr) with a minimum of 3-yr follow-up.

Neonatal hyperparathyroidism with a heterozygous calcium-sensing receptor (CASR) R185Q mutation: clinical benefit from cinacalcet.

Unlabelled: Neonatal hyperparathyroidism can be caused by a heterozygous inactivating mutation in the calcium-sensing receptor. Calcimimetics, allosteric activators of the calcium-sensing receptor, may provide an effective means of reducing PTH secretion in such patients. OBJECTIVE/PATIENT: The objective of the study was to identify the molecular defect and to monitor the postnatal course of a 1-wk-old infant with elevated blood ionized calcium, serum PTH, and alkaline phosphatase and low calcium excretion.

Somatotropin in the treatment of growth hormone deficiency and Turner syndrome in pediatric patients: a review.

Growth hormone (GH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotrophs of the anterior pituitary gland. The main action of GH is to stimulate linear growth in children; however, it also fosters a healthy body composition by increasing muscle and reducing fat mass, maintains normal blood glucose levels, and promotes a favorable lipid profile. This article provides an overview of the normal pathophysiology of GH production and action.

Lack of interaction of milnacipran with the cytochrome p450 isoenzymes frequently involved in the metabolism of antidepressants.

Objective: To compare the pharmacokinetics of milnacipran in extensive metabolisers (EMs) and poor metabolisers (PMs) of sparteine and mephenytoin, and to assess the influence of multiple administrations of milnacipran on the activity of cytochrome P450 (CYP) isoenzymes through its own metabolism and through various probes, namely CYP2D6 (sparteine/dextromethorphan), CYP2C19 (mephenytoin), CYP1A2 (caffeine) and CYP3A4 (endogenous 6-beta-hydroxy-cortisol excretion).

Methods: Twenty-five healthy subjects, 12 EMs for both sparteine/dextromethorphan and mephenytoin, nine EMs for mephenytoin and PMs for sparteine/dextromethorphan (PM(2D6)) and four PMs for mephenytoin and EMs for sparteine/dextromethorphan (PM(2C19)) were administered milnacipran as a single 50 mg capsule on day 1 followed by a 50 mg capsule twice daily for 7 days. The pharmacokinetics of milnacipran and its oxidative metabolites were assessed after the first dose (day 1) and after multiple administration (day 8), and were compared for differences between CYP2D6 and CYP2C19 PMs and EMs.

Evaluation of self-reported skin problems among workers exposed to toluene diisocyanate (TDI) at a foam manufacturing facility.

Toluene diisocyanate, or TDI (CAS 584-84-9) is a well-known asthmagen and respiratory irritant. TDI is also known for its ability to irritate the skin and mucous membranes. To further investigate the dermal effects of TDI, NIOSH investigators conducted a cross-sectional study at a flexible foam manufacturing plant.

Occupational exposure to airborne mercury during gold mining operations near El Callao, Venezuela.

Objective: The National Institute for Occupational Safety and Health (NIOSH) recently conducted a cross-sectional study during gold mining operations near El Callao, Venezuela. The purpose of the study was to assess mercury exposures and mercury-related microdamage to the kidneys. The study consisted of concurrent occupational hygiene and biological monitoring, and an examination of the processing techniques employed at the different mining facilities.

Determination of airborne isocyanate exposure: considerations in method selection.

To assess worker isocyanate exposures in a variety of processes involving the manufacture and use of surface coatings, polyurethane foams, adhesives, resins, elastomers, binders, and sealants, it is important to be able to measure airborne reactive isocyanate-containing compounds. Choosing the correct methodology can be difficult. Isocyanate species, including monomers, prepolymers, oligomers, and polyisocyanates, are capable of producing irritation to the skin, eyes, mucous membranes, and respiratory tract.

Safety, tolerability and pharmacokinetics of the new long-acting quinolone DW-116 after single and multiple dosing in healthy subjects.

The safety, tolerability and pharmacokinetics of DW-116, a new fluoroquinolone with a broad antibacterial spectrum, were evaluated in healthy male subjects after administration of single oral doses of 100, 200, 300 and 800 mg and after administration of multiple oral doses of 300 or 400 mg, respectively, for 7 days. DW-116 was well tolerated. Gastrointestinal symptoms and skin reactions were noted and considered to be possibly related to DW-116.

Indirect assessment of 4,4'-diphenylmethane diisocyanate (MDI) exposure by evaluation of specific humoral immune responses to MDI conjugated to human serum albumin.

Background: A study of occupational asthma among workers exposed to 4,4'-Diphenylmethane Diisocyanate (MDI).

Objective: To demonstrate if serum concentrations of MDI-specific IgG or IgE are sensitive biological markers of disease or of MDI exposure.

Methods: The study group consisted of nine MDI-exposed workers and nine nonexposed workers.