Patient preferences for preventive migraine treatments among Canadian adults: A discrete choice experiment.

Objective: To evaluate preferences for key attributes of injected or infused preventive migraine treatments and assess heterogeneity in preferences among Canadian participants with migraine.

Background: Current treatment options for migraine prevention differ in their attributes, including mode of administration, efficacy, and dosing frequency; preferences for such attributes can vary among patients. With the advent of new therapies, evidence demonstrating patient preferences for injected or infused preventive migraine treatments is necessary.

Migraine Treatment and Healthcare Resource Utilization in Alberta, Canada.

Background: Migraine poses a significant burden worldwide; however, there is limited evidence as to the burden in Canada. This study examined the treatment patterns, healthcare resource use (HRU), and costs among newly diagnosed or recurrent patients with migraine in Alberta, Canada, from the time of diagnosis or recurrence.

Methods: This retrospective observational study utilized administrative health data from Alberta, Canada.

Burden of Episodic Migraine, Chronic Migraine, and Medication Overuse Headache in Alberta.

Objective: To describe demographic and clinical characteristics, healthcare resource use, costs, and treatment patterns in three migraine cohorts.

Methods: This retrospective observational study using administrative data examined patients with episodic migraine (EM), chronic migraine (CM) (without medication overuse headache [MOH]), and medication overuse headache in Alberta, Canada. Migraine patients were identified between 2012 and 2018 based on ≥ 1 diagnostic codes or triptan prescription.

Epidemiology and treatment utilization for Canadian patients with migraine: a literature review.

The objective of this narrative review was to identify real-world evidence regarding the burden of migraine in Canada. We conducted a literature search in MEDLINE, Embase, and the Cochrane Database of Systematic Reviews for studies published between August 2010 and August 2020. Of the 3269 publications identified, 29 studies were included.

Anxiety symptoms in working patients with major depressive disorder treated with vortioxetine: associations with clinical and treatment outcomes in the AtWoRC study.

Background: Anxiety symptoms are common in patients with major depressive disorder (MDD) and usually confer worse treatment outcomes. The long-term, open-label AtWoRC study in working patients with MDD treated with vortioxetine demonstrated a significant correlation between severity of anxiety symptoms and impaired work productivity. This analysis was undertaken to further explore clinical characteristics and treatment outcomes in patients with different levels of severity of anxiety symptoms at baseline.

Improvements in Workplace Productivity in Working Patients With Major Depressive Disorder: Results From the AtWoRC Study.

Objective: To assess changes in workplace productivity and functioning in an open-label study in working patients receiving vortioxetine (10 to 20 mg/d) for major depressive disorder (MDD).

Methods: Associations between items in the Work Limitations Questionnaire (WLQ), the Sheehan Disability Scale (SDS), and the Work Productivity and Activity Impairment (WPAI) questionnaire were assessed at 12 and 52 weeks by Pearson correlation coefficients.

Results: Significant improvements were observed across all domains of workplace productivity and functioning after 12 and 52 weeks' vortioxetine treatment.

Canadian economic impact of improved workplace productivity in patients with major depressive disorder treated with vortioxetine.

Objective: The AtWoRC study is an interventional, open-label Canadian study that demonstrated significant improvements in cognitive function and workplace productivity in patients with major depressive disorder (MDD) treated with vortioxetine for a current major depressive episode. The objective of the present analysis was to assess the Canadian economic impact of improved workplace productivity based on the AtWoRC study results.

Methods: The economic impact of improved productivity in patients with MDD treated with vortioxetine was assessed over a 52-week period considering productivity loss due to absenteeism and presenteeism using the standard human capital approach and an employer's perspective.

Real-life assessment of aripiprazole monthly (Abilify Maintena) in schizophrenia: a Canadian naturalistic non-interventional prospective cohort study.

Background: With previously established efficacy of aripiprazole once-monthly injectable formulation (AOM) in pre-registration randomized controlled trials, the current study was designed to evaluate its effectiveness in patients treated for schizophrenia in regular clinical settings in Canada.

Methods: Following their clinicians' decision to prescribe AOM, 193 patients with a diagnosis of schizophrenia, were recruited from 17 Canadian community or hospital-based settings. The primary outcome of global functioning was assessed with the Global Assessment of Functioning Scale (GAF) at 3-month intervals for 1 year.

Long-term functioning outcomes are predicted by cognitive symptoms in working patients with major depressive disorder treated with vortioxetine: results from the AtWoRC study.

Objective: AtWoRC (Assessment in Work productivity and the Relationship with Cognitive symptoms) was an interventional, open-label, Canadian study (NCT02332954) designed to assess the association between cognitive symptoms and workplace productivity in working patients with major depressive disorder (MDD) receiving vortioxetine.

Methods: Eligible patients with MDD received vortioxetine (10-20 mg/day) and were assessed over 52 weeks at visits emulating a real-life setting (n = 199). Partial correlation between changes in patient-reported cognitive symptoms (20-item Perceived Deficits Questionnaire-Depression; PDQ-D-20) and workplace productivity (Work Limitations Questionnaire; WLQ) was assessed at 12 and 52 weeks.

Assessment in Work Productivity and the Relationship with Cognitive Symptoms (AtWoRC): primary analysis from a Canadian open-label study of vortioxetine in patients with major depressive disorder (MDD).

Objective: The Assessment in Work Productivity and the Relationship with Cognitive Symptoms (AtWoRC) study aimed to assess the association between cognitive symptoms and work productivity in gainfully employed patients receiving vortioxetine for a major depressive episode (MDE).

Methods: Patients diagnosed with major depressive disorder (MDD) and treated with vortioxetine independently of study enrollment were assessed over 52 weeks at visits that emulated a real-life setting. Patients were classified as those receiving vortioxetine as the first treatment for their current MDE (first treatment) or having shown inadequate response to a previous antidepressant (switch).

Structure activity relationships of human galactokinase inhibitors.

Classic Galactosemia is a rare inborn error of metabolism that is caused by deficiency of galactose-1-phosphate uridyltransferase (GALT), an enzyme within the Leloir pathway that is responsible for the conversion of galactose-1-phosphate (gal-1-p) and UDP-glucose to glucose-1-phosphate and UDP-galactose. This deficiency results in elevated intracellular concentrations of its substrate, gal-1-p, and this increased concentration is believed to be the major pathogenic mechanism in Classic Galactosemia. Galactokinase (GALK) is an upstream enzyme of GALT in the Leloir pathway and is responsible for conversion of galactose and ATP to gal-1-p and ADP.

Serotonin-induced cleavage of the atypical protein kinase C Apl III in Aplysia.

A constitutively active kinase, known as protein kinase Mζ (PKMζ), is proposed to act as a long-lasting molecular memory trace. While PKMζ is formed in rodents through translation of a transcript initiating in an intron of the protein kinase Cζ (PKCζ) gene, this transcript does not exist in Aplysia californica despite the fact that inhibitors of PKMζ erase memory in Aplysia in a fashion similar to rodents. We have previously shown that, in Aplysia, the ortholog of PKCζ, PKC Apl III, is cleaved by calpain to form a PKM after overexpression of PKC Apl III.

Time dependence and density inversion in simulations of vertically oscillated granular layers.

We study a layer of grains atop a plate which oscillates sinusoidally in the direction of gravity, using three-dimensional, time-dependent numerical solutions of continuum equations to Navier-Stokes order as well as hard-sphere molecular dynamics simulations. For high accelerational amplitudes of the plate, the layer exhibits a steady-state "density inversion" in which a high-density portion of the layer is supported by a lower-density portion. At low accelerational amplitudes, the layer exhibits oscillatory time dependence that is strongly correlated to the motion of the plate.

2-Oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase.

Compared to normal differentiated cells, cancer cells have altered metabolic regulation to support biosynthesis and the expression of the M2 isozyme of pyruvate kinase (PKM2) plays an important role in this anabolic metabolism. While the M1 isoform is a highly active enzyme, the alternatively spliced M2 variant is considerably less active and expressed in tumors. While the exact mechanism by which decreased pyruvate kinase activity contributes to anabolic metabolism remains unclear, it is hypothesized that activation of PKM2 to levels seen with PKM1 may promote a metabolic program that is not conducive to cell proliferation.

Discovery of potent and selective inhibitors of human platelet-type 12- lipoxygenase.

We report the discovery of novel small molecule inhibitors of platelet-type 12-human lipoxygenase, which display nanomolar activity against the purified enzyme, using a quantitative high-throughput screen (qHTS) on a library of 153607 compounds. These compounds also exhibit excellent specificity, >50-fold selectivity vs the paralogues, 5-human lipoxygenase, reticulocyte 15-human lipoxygenase type-1, and epithelial 15-human lipoxygenase type-2, and >100-fold selectivity vs ovine cyclooxygenase-1 and human cyclooxygenase-2. Kinetic experiments indicate this chemotype is a noncompetitive inhibitor that does not reduce the active site iron.

Potent and selective small molecule inhibitors of specific isoforms of Cdc2-like kinases (Clk) and dual specificity tyrosine-phosphorylation-regulated kinases (Dyrk).

Continued examination of substituted 6-arylquinazolin-4-amines as Clk4 inhibitors resulted in selective inhibitors of Clk1, Clk4, Dyrk1A and Dyrk1B. Several of the most potent inhibitors were validated as being highly selective within a comprehensive kinome scan.

Continuum simulations of shocks and patterns in vertically oscillated granular layers.

We study interactions between shocks and standing-wave patterns in vertically oscillated layers of granular media using three-dimensional, time-dependent numerical solutions of continuum equations to Navier-Stokes order. We simulate a layer of grains atop a plate that oscillates sinusoidally in the direction of gravity. Standing waves form stripe patterns when the accelerational amplitude of the plate's oscillation exceeds a critical value.

Generation of a complete set of additive shape-invariant potentials from an Euler equation.

In supersymmetric quantum mechanics, shape invariance is a sufficient condition for solvability. We show that all conventional additive shape-invariant superpotentials that are independent of ℏ can be generated from two partial differential equations. One of these is equivalent to the one-dimensional Euler equation expressing momentum conservation for inviscid fluid flow, and it is closed by the other.

Aplysia cell adhesion molecule and a novel protein kinase C activity in the postsynaptic neuron are required for presynaptic growth and initial formation of specific synapses.

To explore the role of both Aplysia cell adhesion molecule (ApCAM) and activity of specific protein kinase C (PKC) isoforms in the initial formation of sensory neuron synapses with specific postsynaptic targets (L7 but not L11), we examined presynaptic growth, initial synapse formation, and the expression of the presynaptic neuropeptide sensorin following cell-specific reduction of ApCAM or of a novel PKC activity. Synapse formation between sensory neurons and L7 begins by 3 h after plating and is accompanied by a rapid accumulation of a novel PKC to sites of synaptic interaction. Reducing ApCAM expression specifically from the surface of L7 blocks presynaptic growth and initial synapse formation, target-induced increase of sensorin in sensory neuron cell bodies and the rapid accumulation of the novel PKC to sites of interaction.

Effects of thermal noise on pattern onset in continuum simulations of shaken granular layers.

The author investigates the onset of patterns in vertically oscillated layers of dissipative particles using numerical solutions of continuum equations to Navier-Stokes order. Above a critical accelerational amplitude of the cell, standing waves form stripe patterns which oscillate subharmonically with respect to the cell. Continuum simulations neglecting interparticle friction yield pattern wavelengths consistent with experiments using frictional particles.

Role of protein kinase C in the induction and maintenance of serotonin-dependent enhancement of the glutamate response in isolated siphon motor neurons of Aplysia californica.

Serotonin (5-HT) mediates learning-related facilitation of sensorimotor synapses in Aplysia californica. Under some circumstances 5-HT-dependent facilitation requires the activity of protein kinase C (PKC). One critical site of PKC's contribution to 5-HT-dependent synaptic facilitation is the presynaptic sensory neuron.

The atypical protein kinase C in Aplysia can form a protein kinase M by cleavage.

In vertebrates, a brain-specific transcript from the atypical protein kinase C (PKC) zeta gene encodes protein kinase M (PKM) zeta, a constitutively active kinase implicated in the maintenance of synaptic plasticity and memory. We have cloned the atypical PKC from Aplysia, PKC Apl III. We did not find a transcript in Aplysia encoding PKMzeta, and evolutionary analysis of atypical PKCs suggests formation of this transcript is restricted to vertebrates.

Osteosarcoma of the hand: a rare case for radiographic appearance, location, and age.

Objective: This case describes the history, process of correct diagnosis, and treatment of a patient with pain in her left fourth finger, later found to be an osteosarcoma.

Clinical Features: A 28-year-old woman presented with pain in her left fourth finger, which she also noticed had been "getting bigger." Moderate tenderness and decreased range of motion were noticed over the metacarpophalangeal joint of the involved finger.

Effects of visual feedback on manipulation performance and patient ratings.

Objective: This study examined the explicit targeted outcome (a criterion standard) and visual feedback on the immediate change in and the short-term retention of performance by novice operators for a high-velocity, low-amplitude procedure under realistic conditions.

Methods: This study used a single-blind randomized experimental design. Forty healthy male (n = 26) and female (n = 14) chiropractic student volunteers with no formal training in spinal manipulative therapy participated.