Current State and New Horizons in Applications of Physiologically Based Biopharmaceutics Modeling (PBBM): A Workshop Report.

This report summarizes the proceedings for Day 3 of the workshop titled "". This day focused on the current and future drug product quality applications of PBBM from the innovator and generic industries as well as the regulatory agencies perspectives. The presentations, which included several case studies, covered the applications of PBBM in generic drug product development, applications of virtual bioequivalence trials to support formulation bridging and the utility of absorption modeling in clinical pharmacology assessments.

Hydroaminoalkylation for Amine Functionalization of Vinyl-Terminated Polyethylene Enables Direct Access to Responsive Functional Materials.

While functionalized polyethylenes (PEs) exhibit valuable characteristics, the constraints of existing synthetic approaches limit the variety of readily incorporated functionality. New methods to generate functionalized PEs are required to afford new applications of this common material. We report 100 % atom economic tantalum-catalyzed hydroaminoalkylation of vinyl-terminated polyethylene (VTPE) as a method to produce amine-terminated PE.

PBBM Considerations for Base Models, Model Validation, and Application Steps: Workshop Summary Report.

The proceedings from the 30th August 2023 (Day 2) of the workshop "Physiologically Based Biopharmaceutics Models (PBBM) Best Practices for Drug Product Quality: Regulatory and Industry Perspectives" are provided herein. Day 2 covered PBBM case studies from six regulatory authorities which provided considerations for model verification, validation, and application based on the context of use (COU) of the model. PBBM case studies to define critical material attribute (CMA) specification settings, such as active pharmaceutical ingredient (API) particle size distributions (PSDs) were shared.

'There's more to life than staring at a small screen': a mixed methods cohort study of problematic smartphone use and the relationship to anxiety, depression and sleep in students aged 13-16 years old in the UK.

Background: Depression and anxiety are common in adolescents and have increased over the last decade. During that period, smartphone usage has become ubiquitous.

Objectives: The study aim was to assess the association between problematic smartphone usage (PSU) and anxiety.

Parameterization of Physiologically Based Biopharmaceutics Models: Workshop Summary Report.

This Article shares the proceedings from the August 29th, 2023 (day 1) workshop "Physiologically Based Biopharmaceutics Modeling (PBBM) Best Practices for Drug Product Quality: Regulatory and Industry Perspectives". The focus of the day was on model parametrization; regulatory authorities from Canada, the USA, Sweden, Belgium, and Norway presented their views on PBBM case studies submitted by industry members of the IQ consortium. The presentations shared key questions raised by regulators during the mock exercise, regarding the PBBM input parameters and their justification.

Acceptability, usability, and credibility of a mindfulness-based digital therapeutic for pediatric concussion: A mixed-method study.

Background: The ability to cope with concussion symptoms and manage stress is an important determinant of risk for prolonged symptoms.

Objective: This open-label mixed-methods pilot study assessed the acceptability and credibility of a mindfulness-based intervention delivered through a digital therapeutic (DTx; therapeutic smartphone app) for pediatric concussion.

Methods: Participants aged 12 to 18 years were recruited from an emergency department within 48 hours of a concussion (acute cohort) or from a tertiary care clinic at least 1-month post-concussion (persisting symptoms cohort).

Physiologically Based Biopharmaceutics Modeling (PBBM): Best Practices for Drug Product Quality, Regulatory and Industry Perspectives: 2023 Workshop Summary Report.

Physiologically based biopharmaceutics modeling (PBBM) is used to elevate drug product quality by providing a more accurate and holistic understanding of how drugs interact with the human body. These models are based on the integration of physiological, pharmacological, and pharmaceutical data to simulate and predict drug behavior in vivo. Effective utilization of PBBM requires a consistent approach to model development, verification, validation, and application.

A far-ultraviolet-driven photoevaporation flow observed in a protoplanetary disk.

Most low-mass stars form in stellar clusters that also contain massive stars, which are sources of far-ultraviolet (FUV) radiation. Theoretical models predict that this FUV radiation produces photodissociation regions (PDRs) on the surfaces of protoplanetary disks around low-mass stars, which affects planet formation within the disks. We report James Webb Space Telescope and Atacama Large Millimeter Array observations of a FUV-irradiated protoplanetary disk in the Orion Nebula.

A toolbox for mimicking gastrointestinal conditions in children: Design and evaluation of biorelevant dissolution media for mimicking paediatric gastric- and small intestinal conditions.

The goal of the present work was to develop an in vitro toolbox to evaluate the oral administration of dosage forms to children of different age groups and under different administration conditions (fasted/fed). Based on current data on the gastrointestinal physiology of children, a set of new biorelevant media was designed to mimic the composition and physicochemical properties of resting gastric and resting small intestinal fluid in children of different age groups. In addition, guidelines were developed on how to generate fasted and fed state gastric and small intestinal fluids by combining these media with age-specific drinking volumes or portions of already established simulated paediatric breakfast meals, respectively.

A study protocol for a European, mixed methods, prospective, cohort study of the effectiveness of naloxone administration by community members, in reversing opioid overdose: NalPORS.

Background: Worldwide, opioid use causes more than 100,000 overdose deaths annually. Naloxone has proven efficacy in reversing opioid overdoses and is approved as an emergency antidote to opioid overdose. Take home naloxone (THN) programmes have been introduced to provide 'community members', who are likely to observe opioid overdoses, with naloxone kits and train them to recognise an overdose and administer naloxone.

Magic Numbers and Stabilities of Photoionized Water Clusters: Computational and Experimental Characterization of the Nanosolvated Hydronium Ion.

The stability and distributions of small water clusters generated in a supersonic beam expansion are interrogated by tunable vacuum ultraviolet (VUV) radiation generated at a synchrotron. Time-of-flight mass spectrometry reveals enhanced population of various protonated water clusters (H(HO)) based upon ionization energy and photoionization distance from source, suggesting there are "magic" numbers below the traditional = 21 that predominates in the literature. These intensity distributions suggest that VUV threshold photoionization (11.

Size distribution of polycyclic aromatic hydrocarbons in space: an old new light on the 11.2/3.3 μm intensity ratio.

The intensity ratio of the 11.2/3.3 μm emission bands is considered to be a reliable tracer of the size distribution of polycyclic aromatic hydrocarbons (PAHs) in the interstellar medium (ISM).

Are family medicine residents trained to counsel patients on physical activity? The Canadian experience and a call to action.

Physical inactivity is a leading risk factor for non-communicable diseases (NCDs) and early mortality. Family physicians have an important role in providing physical activity counselling to patients to help prevent and treat NCDs. Lack of training on physical activity counselling is a barrier in undergraduate medical education, yet little is known regarding physical activity teaching in postgraduate family medicine residency.

Compact and automated eDNA sampler for in situ monitoring of marine environments.

Using environmental DNA (eDNA) to monitor biodiversity in aquatic environments is becoming an efficient and cost-effective alternative to other methods such as visual and acoustic identification. Until recently, eDNA sampling was accomplished primarily through manual sampling methods; however, with technological advances, automated samplers are being developed to make sampling easier and more accessible. This paper describes a new eDNA sampler capable of self-cleaning and multi-sample capture and preservation, all within a single unit capable of being deployed by a single person.

Is all validation equal? Evaluating sensory- and emotion-focused validation in the context of experimentally induced pain.

Validation has been examined in experimental and clinical settings, but examination of whether specific content of validation responses affect pain-related outcomes has not been considered. We examined the impact of sensory- or emotion-focused validation following a pain task. Participants ( = 140) were randomly assigned to one of three validation conditions (i.

Smartphone apps for menstrual pain and symptom management: A scoping review.

The past decade marks a surge in the development of mobile apps used to digitally track and monitor aspects of personal health, including menstruation. Despite a plethora of menstruation-related apps, pain and symptom management content available in apps has not been systematically examined. The objective of this study was to evaluate app characteristics, overall quality (i.

Influence of systemic copper toxicity on early development and metamorphosis in Xenopus laevis.

The primary objective of the present study was to examine the influence of early systemic toxicity resulting from copper (Cu) exposure on metamorphic processes in Xenopus laevis. A 28-day exposure study with copper, initiated at developmental stage 10, was performed using test concentrations of 3.0, 9.

Inhalation toxicity of copper compounds: Results of 14-day range finding study for copper sulphate pentahydrate and dicopper oxide and 28-day subacute inhalation exposure of dicopper oxide in rats.

Inhalation exposure to copper may occur during a range of occupational activities and the purpose of this study was to characterise the toxicological response to repeated inhalation of two copper compounds, representative of copper substances in large-scale production/use. Crl:CD(SD) rats were repeatedly exposed to aerosols of dicopper oxide (CuO) or copper sulphate pentahydrate (CuSO.5 HO) for 14-days as part of a range finding study at normalised copper doses of 0.

Developing Clinically Relevant Dissolution Specifications (CRDSs) for Oral Drug Products: Virtual Webinar Series.

A webinar series that was organised by the Academy of Pharmaceutical Sciences Biopharmaceutics focus group in 2021 focused on the challenges of developing clinically relevant dissolution specifications (CRDSs) for oral drug products. Industrial scientists, together with regulatory and academic scientists, came together through a series of six webinars, to discuss progress in the field, emerging trends, and areas for continued collaboration and harmonisation. Each webinar also hosted a Q&A session where participants could discuss the shared topic and information.

Anharmonicity and the IR Emission Spectrum of Neutral Interstellar PAH Molecules.

The characteristics of the CH stretching and out-of-plane bending modes in polycyclic aromatic hydrocarbon molecules are investigated using anharmonic density functional theory (DFT) coupled to a vibrational second-order perturbation treatment taking resonance effects into account. The results are used to calculate the infrared emission spectrum of vibrationally excited species in the collision-less environment of interstellar space. This model follows the energy cascade as the molecules relax after the absorption of a UV photon in order to calculate the detailed profiles of the infrared bands.

A Computational and Experimental View of Hydrogen Bonding in Glycerol Water Clusters.

Polyol-water clusters provide a template to probe ionization and solvation processes of paramount interest in atmospheric and interstellar chemistry. We generate glycerol water clusters in a continuous supersonic jet expansion and interrogate the neutral species with synchrotron-based tunable vacuum ultraviolet photoionization mass spectrometry. A series of glycerol fragments (/ 44, 61, 62, and 74) clustered with water are observed.

Modeling the infrared cascade spectra of small PAHs: the 11.2 μm band.

The profile of the 11.2 μm feature of the infrared (IR) cascade emission spectra of polycyclic aromatic hydrocarbon (PAH) molecules is investigated using a vibrational anharmonic method. Several factors are found to affect the profile including: the energy of the initially absorbed ultraviolet (UV) photon, the density of vibrational states, the anharmonic nature of the vibrational modes, the relative intensities of the vibrational modes, the rotational temperature of the molecule, and blending with nearby features.

Bioaccessibility as a determining factor in the bioavailability and toxicokinetics of cadmium compounds.

Cadmium toxicity occurs where there is absorption and accumulation of cadmium ions (Cd) in tissues beyond tolerable levels. Significant differences in the release of Cd from cadmium compounds in biological fluids, like gastric fluid, may indicate differences in bioavailability and absorption. This means that direct read-across from high solubility cadmium compounds to lower solubility compounds may not accurately reflect potential hazards.