Using implementation science to evaluate longitudinal assessment of entrustable professional activities in dental education.

Purpose: To evaluate the implementation of a longitudinal assessment framework utilizing entrustable professional activities (EPAs) in dental education during the initial 2-year implementation.

Method: The Consolidated Framework for Implementation Research was utilized to evaluate contextual factors influencing implementation across the following domains: innovation, outer setting, inner setting, individuals, and process. Purposive sampling was used to ascertain a diverse pool of participants and various perspectives.

Developing entrustable professional activities for general dentistry at the University of North Carolina.

Introduction: As part of curriculum innovation, the University of North Carolina (UNC) Adams School of Dentistry identified core entrustable professional activities (EPAs) that graduates must demonstrate for practice readiness. This paper describes the development of the UNC EPAs and the perceptions of the general dentistry faculty.

Methods: Upon establishing a blueprint of knowledge, skills, and attitudes of UNC graduates, using a distributed leadership approach, faculty teams developed EPAs focused on the patient care process.

TRPA1 Antagonist LY3526318 Inhibits the Cinnamaldehyde-Evoked Dermal Blood Flow Increase: Translational Proof of Pharmacology.

Transient receptor potential Ankyrin 1 (TRPA1) is an ion channel expressed by sensory neurons, where it mediates pain signaling. Consequently, it has emerged as a promising target for novel analgesics, yet, to date, no TRPA1 antagonists have been approved for clinical use. In the present translational study, we utilized dermal blood flow changes evoked by TRPA1 agonist cinnamaldehyde as a target engagement biomarker to investigate the in vivo pharmacology of LY3526318, a novel TRPA1 antagonist.

The test-retest reliability of large and small fiber nerve excitability testing with threshold tracking.

Objective: Standard nerve excitability testing (NET) predominantly assesses Aα- and Aβ-fiber function, but a method examining small afferents would be of great interest in pain studies. Here, we examined the properties of a novel perception threshold tracking (PTT) method that preferentially activates Aδ-fibers using weak currents delivered by a novel multipin electrode and compared its reliability with NET.

Methods: Eighteen healthy subjects (mean age:34.

Critical thinking in musicians' health education. Findings from four workshops with experts (Part I).

Health education encompasses building health knowledge, but also training skills such as critical thinking, that guide individuals' ability to access, understand and use health information to take care of their own health (WHO, 1998). This study aimed to document expert discussions on the content of an ideal health education curriculum for higher music education (HME) students in the UK, integrating critical thinking. Four interdisciplinary workshops were conducted, where 67 experts in relevant fields discussed the content of four lists created based on literature reviews (cognitive biases, logical fallacies, critical appraisal tools and health topics).

Health education in conservatoires: what should it consist of? Findings from workshops with experts (Part II).

Although health education programmes have been implemented in higher music education (HME) and their evaluations published in peer-reviewed journals, guidelines as to what ought to be included in these programmes are still missing. This study aimed to document expert discussions on the content of an ideal health education curriculum for HME students in the UK, integrating critical thinking. Four interdisciplinary workshops were conducted, where 67 experts in relevant fields took part, and were asked to discuss four lists of topics and concepts created based on literature reviews (cognitive biases, logical fallacies, critical appraisal tools and health topics).

IMI2-PainCare-BioPain-RCT2 protocol: a randomized, double-blind, placebo-controlled, crossover, multicenter trial in healthy subjects to investigate the effects of lacosamide, pregabalin, and tapentadol on biomarkers of pain processing observed by non-invasive neurophysiological measurements of human spinal cord and brainstem activity.

Background: IMI2-PainCare-BioPain-RCT2 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on specific compartments of the nociceptive system that could serve to accelerate the future development of analgesics. IMI2-PainCare-BioPain-RCT2 will focus on human spinal cord and brainstem activity using biomarkers derived from non-invasive neurophysiological measurements.

Methods: This is a multisite, single-dose, double-blind, randomized, placebo-controlled, 4-period, 4-way crossover, pharmacodynamic (PD) and pharmacokinetic (PK) study in healthy subjects.

Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development.

There is an urgent need for analgesics with improved efficacy, especially in neuropathic and other chronic pain conditions. Unfortunately, in recent decades, many candidate analgesics have failed in clinical phase II or III trials despite promising preclinical results. Translational assessment tools to verify engagement of pharmacological targets and actions on compartments of the nociceptive system are missing in both rodents and humans.

Preparing for implementation of an entrustable professional activity assessment framework.

Following the adoption of competency-based education in dentistry in the 1990s, entrustable professional activities (EPAs) were introduced in the field of medicine in the mid-2000s to help educators better determine the competence of trainees. More recently, the field of dental education has begun exploring EPAs as a framework for assessing competence while ensuring compliance with accreditation standards. This paper explores one dental school's process of preparing for implementation of a major curriculum change using an EPA assessment framework, shifting away from the use of singular assessments for competency determination to a global and longitudinal approach using a constellation of data to determine practice readiness.

IMI2-PainCare-BioPain-RCT1: study protocol for a randomized, double-blind, placebo-controlled, crossover, multi-center trial in healthy subjects to investigate the effects of lacosamide, pregabalin, and tapentadol on biomarkers of pain processing observed by peripheral nerve excitability testing (NET).

Background: Few new drugs have been developed for chronic pain. Drug development is challenged by uncertainty about whether the drug engages the human target sufficiently to have a meaningful pharmacodynamic effect. IMI2-PainCare-BioPain-RCT1 is one of four similarly designed studies that aim to link different functional biomarkers of drug effects on the nociceptive system that could serve to accelerate the future development of analgesics.

Plasticity in visual cortex is disrupted in a mouse model of tauopathy.

Alzheimer's disease and other dementias are thought to underlie a progressive impairment of neural plasticity. Previous work in mouse models of Alzheimer's disease shows pronounced changes in artificially-induced plasticity in hippocampus, perirhinal and prefrontal cortex. However, it is not known how degeneration disrupts intrinsic forms of brain plasticity.

Evaluating the association of TRPA1 gene polymorphisms with pain sensitivity: a protocol for an adaptive recall by genotype study.

Background: Pain is a complex polygenic trait whose common genetic underpinnings are relatively ill-defined due in part to challenges in measuring pain as a phenotype. Pain sensitivity can be quantified, but this is difficult to perform at the scale required for genome wide association studies (GWAS). Existing GWAS of pain have identified surprisingly few loci involved in nociceptor function which contrasts strongly with rare monogenic pain states.

From structure to clinic: Design of a muscarinic M1 receptor agonist with potential to treatment of Alzheimer's disease.

Current therapies for Alzheimer's disease seek to correct for defective cholinergic transmission by preventing the breakdown of acetylcholine through inhibition of acetylcholinesterase, these however have limited clinical efficacy. An alternative approach is to directly activate cholinergic receptors responsible for learning and memory. The M1-muscarinic acetylcholine (M1) receptor is the target of choice but has been hampered by adverse effects.

The N13 spinal component of somatosensory evoked potentials is modulated by heterotopic noxious conditioning stimulation suggesting an involvement of spinal wide dynamic range neurons.

Objectives: Although somatosensory evoked potentials (SEPs) after median nerve stimulation are widely used in clinical practice, the dorsal horn generator of the N13 SEP spinal component is not clearly understood. To verify whether wide dynamic range neurons in the dorsal horn of the spinal cord are involved in the generation of the N13 SEP, we tested the effect of heterotopic noxious conditioning stimulation, which modulates wide dynamic range neurons, on N13 SEP in healthy humans.

Methods: In 12 healthy subjects, we performed the cold pressor test on the left foot as a heterotopic noxious conditioning stimulus to modulate wide dynamic range neurons.

IMI2-PainCare-BioPain-RCT3: a randomized, double-blind, placebo-controlled, crossover, multi-center trial in healthy subjects to investigate the effects of lacosamide, pregabalin, and tapentadol on biomarkers of pain processing observed by electroencephalography (EEG).

Background: IMI2-PainCare-BioPain-RCT3 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on the nociceptive system that could serve to accelerate the future development of analgesics, by providing a quantitative understanding between drug exposure and effects of the drug on nociceptive signal processing in human volunteers. IMI2-PainCare-BioPain-RCT3 will focus on biomarkers derived from non-invasive electroencephalographic (EEG) measures of brain activity.

Methods: This is a multisite single-dose, double-blind, randomized, placebo-controlled, 4-period, 4-way crossover, pharmacodynamic (PD) and pharmacokinetic (PK) study in healthy subjects.

Impaired speed encoding and grid cell periodicity in a mouse model of tauopathy.

Dementia is associated with severe spatial memory deficits which arise from dysfunction in hippocampal and parahippocampal circuits. For spatially sensitive neurons, such as grid cells, to faithfully represent the environment these circuits require precise encoding of direction and velocity information. Here, we have probed the firing rate coding properties of neurons in medial entorhinal cortex (MEC) in a mouse model of tauopathy.

Targeting the Synapse in Alzheimer's Disease.

Dynamic gain and loss of synapses is fundamental to healthy brain function. While Alzheimer's Disease (AD) treatment strategies have largely focussed on beta-amyloid and tau protein pathologies, the synapse itself may also be a critical endpoint to consider regarding disease modification. Disruption of mechanisms of neuronal plasticity, eventually resulting in a net loss of synapses, is implicated as an early pathological event in AD.

Initiation and slow propagation of epileptiform activity from ventral to dorsal medial entorhinal cortex is constrained by an inhibitory gradient.

Key Points: The medial entorhinal cortex (mEC) has an important role in initiation and propagation of seizure activity. Several anatomical relationships exist in neurophysiological properties of mEC neurons; however, in the context of hyperexcitability, previous studies often considered it as a homogeneous structure. Using multi-site extracellular recording techniques, ictal-like activity was observed along the dorso-ventral axis of the mEC in vitro in response to various ictogenic stimuli.

First record of the species complex in the American Gulf of Mexico Coastline, as confirmed by morphological and molecular approaches.

isopods exhibit a constrained morphology that makes identification difficult. In the Greater Caribbean, a convoluted taxonomic history has left the distributional limits of unclear. To date, no confirmed records of this species exist from the American Gulf of Mexico.

Tracking progressive pathological and functional decline in the rTg4510 mouse model of tauopathy.

Background: The choice and appropriate use of animal models in drug discovery for Alzheimer's disease (AD) is pivotal to successful clinical translation of novel therapeutics, yet true alignment of research is challenging. Current models do not fully recapitulate the human disease, and even exhibit various degrees of regional pathological burden and diverse functional alterations. Given this, relevant pathological and functional endpoints must be determined on a model-by-model basis.

TaiNi: Maximizing research output whilst improving animals' welfare in neurophysiology experiments.

Understanding brain function at the cell and circuit level requires representation of neuronal activity through multiple recording sites and at high sampling rates. Traditional tethered recording systems restrict movement and limit the environments suitable for testing, while existing wireless technology is still too heavy for extended recording in mice. Here we tested TaiNi, a novel ultra-lightweight (<2 g) low power wireless system allowing 72-hours of recording from 16 channels sampled at ~19.

Coordinated Acetylcholine Release in Prefrontal Cortex and Hippocampus Is Associated with Arousal and Reward on Distinct Timescales.

Cholinergic neurotransmission throughout the neocortex and hippocampus regulates arousal, learning, and attention. However, owing to the poorly characterized timing and location of acetylcholine release, its detailed behavioral functions remain unclear. Using electrochemical biosensors chronically implanted in mice, we made continuous measurements of the spatiotemporal dynamics of acetylcholine release across multiple behavioral states.