A developmental assessment of clinical reasoning in preclinical medical education.

Background: Clinical reasoning is an essential skill to be learned during medical education. A developmental framework for the assessment and measurement of this skill has not yet been described in the literature.

Objective: The authors describe the creation and pilot implementation of a rubric designed to assess the development of clinical reasoning skills in pre-clinical medical education.

Registration of a statistical model to intraoperative ultrasound for scaphoid screw fixation.

Purpose: Volar percutaneous scaphoid fracture fixation is conventionally performed under fluoroscopy-based guidance, where surgeons need to mentally determine a trajectory for the insertion of the screw and its depth based on a series of 2D projection images. In addition to challenges associated with mapping 2D information to a 3D space, the process involves exposure to ionizing radiation. Three-dimensional ultrasound has been suggested as an alternative imaging tool for this procedure; however, it has not yet been integrated into clinical routine since ultrasound only provides a limited view of the scaphoid and its surrounding anatomy.

Automatic Segmentation of Wrist Bones in CT Using a Statistical Wrist Shape + Pose Model.

Segmentation of the wrist bones in CT images has been frequently used in different clinical applications including arthritis evaluation, bone age assessment and image-guided interventions. The major challenges include non-uniformity and spongy textures of the bone tissue as well as narrow inter-bone spaces. In this work, we propose an automatic wrist bone segmentation technique for CT images based on a statistical model that captures the shape and pose variations of the wrist joint across 60 example wrists at nine different wrist positions.

Bone enhancement in ultrasound using local spectrum variations for guiding percutaneous scaphoid fracture fixation procedures.

Purpose: The scaphoid bone is the most frequently fractured bone in the wrist. When fracture fixation is indicated, a screw is inserted into the bone either in an open surgical procedure or percutaneously under fluoroscopic guidance. Due to the complex geometry of the wrist, fracture fixation is a challenging task.

Competing molecular interactions of aPKC isoforms regulate neuronal polarity.

Atypical protein kinase C (aPKC) isoforms ζ and λ interact with polarity complex protein Par3 and are evolutionarily conserved regulators of cell polarity. Prkcz encodes aPKC-ζ and PKM-ζ, a truncated, neuron-specific alternative transcript, and Prkcl encodes aPKC-λ. Here we show that, in embryonic hippocampal neurons, two aPKC isoforms, aPKC-λ and PKM-ζ, are expressed.

A novel nicotinic mechanism underlies β-amyloid-induced neuronal hyperexcitation.

There is a significantly elevated incidence of epilepsy in Alzheimer's disease (AD). Moreover, there is neural hyperexcitation/synchronization in transgenic mice expressing abnormal levels or forms of amyloid precursor protein and its presumed, etiopathogenic product, amyloid-β1-42 (Aβ). However, the underlying mechanisms of how Aβ causes neuronal hyperexcitation remain unclear.

Volume slicing of cone-beam computed tomography images for navigation of percutaneous scaphoid fixation.

Purpose: Percutaneous scaphoid fixation (PSF) is growing in popularity as a treatment option for non-displaced fractures. Success of this procedure demands high-precision screw placement, which can be difficult to achieve with standard 2D imaging. This study aimed to develop and test a system for computer-assisted navigation using volume slicing of 3D cone-beam computed tomography (CBCT).

Accuracy of single-plane fluoroscopy in determining relative position and orientation of total knee replacement components.

The accuracy of estimating the relative pose between knee replacement components, in terms of clinical motion, is important in the study of knee joint kinematics. The objective of this study was to determine the accuracy of the single-plane fluoroscopy method in calculating the relative pose between the femoral component and the tibial component, along knee motion axes, while the components were in motion relative to one another. The kinematics of total knee replacement components were determined in vitro using two simultaneous methods: single-plane fluoroscopic shape matching and an optoelectronic motion tracking system.

Calibration and use of intraoperative cone-beam computed tomography: an in-vitro study for wrist fracture.

The standard workflow in many image-guided procedures, preoperative imaging followed by intraoperative registration, can be a challenging process and is not readily adaptable to certain anatomical regions such as the wrist. In this study we present an alternative, consisting of a preoperative registration calibration and intraoperative navigation using 3D cone-beam CT. A custom calibration tool was developed to preoperatively register an optical tracking system to the imaging space of a digital angiographic C-arm.

Cellular trafficking of nicotinic acetylcholine receptors.

Nicotinic acetylcholine receptors (nAChRs) play critical roles throughout the body. Precise regulation of the cellular location and availability of nAChRs on neurons and target cells is critical to their proper function. Dynamic, post-translational regulation of nAChRs, particularly control of their movements among the different compartments of cells, is an important aspect of that regulation.

Sustained cannabinoid agonist treatment augments CGRP release in a PKA-dependent manner.

Studies have shown that sustained cannabinoid treatment increases the sensitivity to painful heat stimuli (thermal hyperalgesia) and innocuous mechanical stimuli (tactile allodynia). It has been suggested that augmented release of pain neurotransmitters (such as calcitonin gene-related peptide, CGRP) might be responsible for this abnormal pain sensitization. We hypothesize that intracellular adaptations upon sustained cannabinoid treatment causes augmented release of CGRP from primary nociceptors leading to increased pain sensitivity.

Sustained morphine treatment augments basal CGRP release from cultured primary sensory neurons in a Raf-1 dependent manner.

Recent studies suggest that sustained morphine-mediated paradoxical pain may play an important role in the development of analgesic tolerance. The intracellular signal transduction pathways involved in sustained opioid mediated augmentation of spinal pain neurotransmitter (such as calcitonin gene-related peptide (CGRP)) release are not fully clarified. Cyclic AMP (cAMP)-dependent protein kinase (PKA) plays an important role in the modulation of presynaptic neurotransmitter release.

Differential binding and activation of caspase-3 in cultured hippocampal neurons by assembly forms of A beta 1-42.

Amyloid-beta (A beta) peptides, the primary constituents of amyloid plaques in the brain in Alzheimer's disease (AD), may cause AD, but how they do so is not clear. A beta peptides spontaneously aggregate, or self-assemble, to generate several distinct macromolecular and morphological forms that can differ significantly in their effects on cells. We have compared different assembly forms of A beta(1-42) (A beta 42) for their ability to trigger apoptosis in cultured hippocampal neurons at a submicromolar concentration and for their binding to such neurons.

Iptakalim modulates ATP-sensitive K(+) channels in dopamine neurons from rat substantia nigra pars compacta.

Iptakalim, a novel cardiovascular ATP-sensitive K(+) (K(ATP)) channel opener, exerts neuroprotective effects on dopaminergic (DA) neurons against metabolic stress-induced neurotoxicity, but the mechanisms are largely unknown. Here, we examined the effects of iptakalim on functional K(ATP) channels in the plasma membrane (pm) and mitochondrial membrane using patch-clamp and fluorescence-imaging techniques. In identified DA neurons acutely dissociated from rat substantia nigra pars compacta (SNc), both the mitochondrial metabolic inhibitor rotenone and the sulfonylurea receptor subtype (SUR) 1-selective K(ATP) channel opener (KCO) diazoxide induced neuronal hyperpolarization and abolished action potential firing, but the SUR2B-selective KCO cromakalim exerted little effect, suggesting that functional K(ATP) channels in rat SNc DA neurons are mainly composed of SUR1.

Roles of nicotinic acetylcholine receptor beta subunits in function of human alpha4-containing nicotinic receptors.

Naturally expressed nicotinic acetylcholine receptors (nAChR) containing alpha4 subunits (alpha4*-nAChR) in combination with beta2 subunits (alpha4beta2-nAChR) are among the most abundant, high-affinity nicotine binding sites in the mammalian brain. beta4 subunits are also richly expressed and colocalize with alpha4 subunits in several brain regions implicated in behavioural responses to nicotine and nicotine dependence. Thus, alpha4beta4-nAChR also may exist and play important functional roles.

Electrophysiological properties of human hypothalamic hamartomas.

The hypothalamic hamartoma (HH) is a rare developmental malformation often characterized by gelastic seizures, which are usually refractory to medical therapy. The mechanisms of epileptogenesis operative in this subcortical lesion are unknown. In this study, we used standard patch-clamp electrophysiological techniques combined with histochemical approaches to study individual cells from human HH tissue immediately after surgical resection.

Role of Nova-1 in regulating alpha2N, a novel glycine receptor splice variant, in developing spinal cord neurons.

Inhibitory glycine receptor (GlyR) subunits undergo developmental regulation, but the molecular mechanisms of GlyR regulation in developing neurons are little understood. Using RT-PCR, we investigated the regulation of GlyR alpha-subunit splice forms during the development of the spinal cord of the rat. Experiments to compare the amounts of mRNA for two known splice variants of the GlyR alpha2 subunit, alpha2A and alpha2B, in the developing rat spinal cord revealed the presence of an additional, novel variant that lacked any exon 3, herein named "alpha2N.

Expression of alpha(2)-adrenergic receptor subtypes in prenatal rat spinal cord.

The results of molecular cloning have revealed three subtypes of the alpha(2)-adrenergic receptors (alpha(2) AR) that have been defined alpha(2)C10 (alpha(2A)), alpha(2)C2 (alpha(2B)) and alpha(2)C4 (alpha(2C)). The differential expression of alpha(2) AR subtypes is affected by developmental factors in rat submandibular gland, lung and brain. In the spinal cord of postnatal and adult rats, alpha(2A) and alpha(2C) AR subtypes are expressed and appear to mediate pain perception.