Expedient Synthesis of Thermally Stable Acyclic Amino(haloaryl)carbenes: Experimental and Theoretical Evidence of "Push-Pull" Stabilized Carbenes.

A library of novel structurally related singlet carbenes, namely, acyclic amino(haloaryl)carbenes, was designed by a high-yielding two-step procedure, and their chemical stability explored both experimentally and theoretically. Thanks to a careful selection of both the amino and the aryl substitution pattern, these carbenes exhibit a wide range of stability and reactivity, spanning from rapid self-dimerization for carbenes featuring -F substituents to very high chemical stability as bare carbenes, up to 60 °C for several hours for compounds carrying -Br substituents. Their structure was determined through NMR and X-ray diffraction studies, and their reactivity evaluated in benchmark reactions, highlighting the ambiphilic character of this novel class of singlet carbenes.

Exploring the Therapeutic Potential of Quadripulse rTMS over the Visual Cortex: A Proof-of-Concept Study in Healthy Volunteers and Chronic Migraine Patients with Medication Overuse Headache.

In chronic migraine with medication overuse (CM-MOH), sensitization of visual cortices is reflected by (i) increased amplitude of stimulus-evoked responses and (ii) habituation deficit during repetitive stimulation. Both abnormalities might be mitigated by inhibitory transcranial neurostimulation. Here, we tested an inhibitory quadripulse repetitive transcranial magnetic stimulation (rTMS-QPI) protocol to decrease durably visual cortex excitability in healthy subjects (HS) and explored its therapeutic potential in CM-MOH patients.

Combining Item Purification and Multiple Comparison Adjustment Methods in Detection of Differential Item Functioning.

Many of the differential item functioning (DIF) detection methods rely on a principle of testing for DIF item by item, while considering the rest of the items or at least some of them being DIF-free. Computational algorithms of these DIF detection methods involve the selection of DIF-free items in an iterative procedure called . Another aspect is the need to correct for multiple comparisons, which can be done with a number of existing methods.

Neuromodulation for Chronic Daily Headache.

Purpose Of Review: We reviewed the literature that explored the use of central and peripheral neuromodulation techniques for chronic daily headache (CDH) treatment.

Recent Findings: Although the more invasive deep brain stimulation (DBS) is effective in chronic cluster headache (CCH), it should be reserved for extremely difficult-to-treat patients. Percutaneous occipital nerve stimulation has shown similar efficacy to DBS and is less risky in both CCH and chronic migraine (CM).

Direct and selective access to amino-poly(phenylene vinylenes)s with switchable properties by dimerizing polymerization of aminoaryl carbenes.

Despite the ubiquity of singlet carbenes in chemistry, their utility as true monomeric building blocks for the synthesis of functional organic polymers has been underexplored. In this work, we exploit the capability of purposely designed mono- and bis-acyclic amino(aryl)carbenes to selectively dimerize as a general strategy to access diaminoalkenes and hitherto unknown amino-containing poly(p-phenylene vinylene)s (N-PPV's). The unique selectivity of the dimerization of singlet amino(aryl)carbenes, relative to putative C-H insertion pathways, is rationalized by DFT calculations.

Guidelines of the International Headache Society for clinical trials with neuromodulation devices for the treatment of migraine.

Background: Although the European Medicines Agency and the US Food and Drug Administration have cleared several devices that use neuromodulation to provide clinical benefits in the acute or preventive treatment of migraine, the Clinical Trials Committee of the International Headache Society has not developed guidelines specifically for clinical trials of neuromodulation devices. In recognition of the distinct needs and challenges associated with their assessment in controlled trials, the Committee provides these recommendations for optimizing the design and conduct of controlled trials of neuromodulation devices for the acute and/or preventive treatment of migraine.

Methods: An international group of headache scientists and clinicians with expertise in neuromodulation evaluated clinical trials involving neuromodulation devices that have been published since 2000.

On the Developmental Trajectories of Relational Concepts Among Children and Adolescents With Intellectual Disability of Undifferentiated Etiology.

The aim of this study was to examine the developmental trajectories of comprehension of relational concepts among 557 participants with intellectual disability (ID) of undifferentiated etiology (M age  =  12.20 years, SD  =  3.18) and 557 typically developing (TD) participants (M age  =  4.

Evaluation of 2-Hour Post-Dose Efficacy of Lasmiditan for the Acute Treatment of Difficult-to-Treat Migraine Attacks.

Objective: To identify factors predicting response (2-hour headache pain freedom or most bothersome symptom freedom) to lasmiditan based on individual patient characteristics, migraine disease characteristics, and migraine attack characteristics. Further, efficacy specifically in difficult-to-treat patient/migraine disease characteristics or attack characteristics (ie, historically considered less responsive to certain acute therapies) subgroups was analyzed.

Background: Knowledge of factors associated with a positive or negative response to acute treatment would be useful to practitioners prescribing acute treatments for migraine.

Efficient Standard Errors in Item Response Theory Models for Short Tests.

In dichotomous item response theory (IRT) framework, the asymptotic standard error (ASE) is the most common statistic to evaluate the precision of various ability estimators. Easy-to-use ASE formulas are readily available; however, the accuracy of some of these formulas was recently questioned and new ASE formulas were derived from a general asymptotic theory framework. Furthermore, exact standard errors were suggested to better evaluate the precision of ability estimators, especially with short tests for which the asymptotic framework is invalid.

Development of potent inhibitors of the human microsomal epoxide hydrolase.

Microsomal epoxide hydrolase (mEH) hydrolyzes a wide range of epoxide containing molecules. Although involved in the metabolism of xenobiotics, recent studies associate mEH with the onset and development of certain disease conditions. This phenomenon is partially attributed to the significant role mEH plays in hydrolyzing endogenous lipid mediators, suggesting more complex and extensive physiological functions.

Correction to: Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies.

Following publication of the original article [1], the authors noticed an error in the values for 'Hypersensitivity SMQ' and 'Rash' in Table 7.

The function of the lateral inhibitory mechanisms in the somatosensory cortex is normal in patients with chronic migraine.

Objective: To study lateral inhibition and habituation/sensitization in the somatosensory cortex of patients with chronic migraine (CM) and to identify correlations with clinical migraine features.

Methods: Sixteen patients with CM without medication overuse, and 17 healthy volunteers (HVs) received somatosensory evoked potentials (SSEPs) elicited by separate electrical stimulation of the right median (M) and ulnar (U) nerves at the wrist and by simultaneous nerve stimulation (MU). We measured the N20-P25 amplitudes and calculated the lateral inhibition (LI) percentage using the formula {100-[MU/(M + U) * 100]}.

Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies.

Background: Galcanezumab, a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide, has demonstrated a significant reduction in monthly migraine headache days in phase 2 and 3 trials. In these analyses, we aimed to evaluate the safety and tolerability of galcanezumab compared with placebo for prevention of episodic or chronic migraine.

Methods: Data were integrated from three double-blind clinical studies for the up to 6-month galcanezumab exposure group (N = 1435), and from five clinical studies for the up to 1-year all-galcanezumab exposure group (N = 2276).

Headache Related Alterations of Visual Processing in Migraine Patients.

Migraine is characterized by an increased sensitivity to visual stimuli that worsens during attacks. Recent evidence has shown that feedforward volleys carrying incoming visual information induce high-frequency (gamma) oscillations in the visual cortex, while feedback volleys arriving from higher order brain areas induce oscillatory activity at lower frequencies (theta/alpha/low beta). We investigated visually induced high (feedforward) and low (feedback) frequency activations in healthy subjects and various migraine patients.

Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial.

Introduction: Non-invasive vagus nerve stimulation (nVNS; gammaCore®) has the potential to prevent migraine days in patients with migraine on the basis of mechanistic rationale and pilot clinical data.

Methods: This multicentre study included a 4-week run-in period, a 12-week double-blind period of randomised treatment with nVNS or sham, and a 24-week open-label period of nVNS. Patients were to administer two 120-second stimulations bilaterally to the neck three times daily (6-8 hours apart).

Emerging treatments for cluster headache: hopes and disappointments.

Purpose Of Review: Cluster headache stands among the worst debilitating pain conditions. Available treatments for cluster headache have often disabling side effects, are not tolerated, or are ineffective. The management of drug-refractory chronic forms is challenging.

Does the Development of Syntax Comprehension Show a Premature Asymptote Among Persons With Down Syndrome? A Cross-Sectional Analysis.

Uncertainty persists regarding the post-childhood trajectory of syntactic acquisition of persons with Down syndrome (DS). In some studies, asymptote is reached in the early teens, whereas others find syntax continuing to develop at least into early adulthood. This study addressed the issue using a cross-sectional approach.

Age related metabolic modifications in the migraine brain.

Purpose: The aim of this study was to evaluate the possibility that migraine patients exhibit specific age-related metabolic changes in the brain, which occur regardless of disease duration or the frequency of attacks.

Methods: We analysed the relation between brain glucose (F-fluorodeoxyglucose) uptake and age in healthy volunteers (n = 20) and episodic migraine patients (n = 19). In the latter, we additionally compared the correlation between F-fluorodeoxyglucose uptake and disease duration and monthly migraine days.

Anodal frontal tDCS for chronic cluster headache treatment: a proof-of-concept trial targeting the anterior cingulate cortex and searching for nociceptive correlates.

Background: Percutaneous occipital nerve stimulation (ONS) is effective in refractory chronic cluster headache (rCCH) patients. Responders to ONS differ from non-responders by greater glucose metabolism in subgenual anterior cingulate cortex (sgACC). We reasoned that transcranial direct current stimulation (tDCS), a non-invasive approach, might be able to activate this area and thus improve rCCH patients.

Evidence of an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients: a study comparing FDG-PET and visual evoked potentials.

Background: Migraine attacks might be triggered by a disruption of cerebral homeostasis. During the interictal period migraine patients are characterized by abnormal sensory information processing, but this functional abnormality may not be sufficient to disrupt the physiological equilibrium of the cortex unless it is accompanied by additional pathological mechanisms, like a reduction in energetic reserves. The aim of this study was to compare resting cerebral glucose uptake (using positron emission tomography (fluorodeoxyglucose-PET)), and visual cortex activation (using visual evoked potentials (VEP)), between episodic migraine without aura patients in the interictal period and healthy volunteers.

Electrophysiological Characteristics of the Migraine Brain: Current Knowledge and Perspectives.

Background: Despite pain being its most prominent feature, migraine is primarily a disorder of sensory processing. Electrophysiology-based research in the field has consistently developed over the last fifty years.

Objective: To summarize the current knowledge on the electrophysiological characteristics of the migraine brain, and discuss perspectives.

Brain Correlates of Single Trial Visual Evoked Potentials in Migraine: More Than Meets the Eye.

Using conventional visual evoked potentials (VEPs), migraine patients were found to be hyperresponsive to visual stimulus. Considering that a significant portion of neuronal activity is lost for analysis in the averaging process of conventional VEPs, in this study we investigated visual evoked responses of migraine patients and healthy volunteers using a different approach: single trial analysis. This method permits to preserve all stimulus-induced neuronal activations, whether they are synchronized or not.

Basic visual perceptual processes in children with typical development and cerebral palsy: The processing of surface, length, orientation, and position.

The present study aims to assess how the processing of basic visual perceptual (VP) components (length, surface, orientation, and position) develops in typically developing (TD) children (n = 215, 4-14 years old) and adults (n = 20, 20-25 years old), and in children with cerebral palsy (CP) (n = 86, 5-14 years old) using the first four subtests of the Battery for the Evaluation of Visual Perceptual and Spatial processing in children. Experiment 1 showed that these four basic VP processes follow distinct developmental trajectories in typical development. Experiment 2 revealed that children with CP present global and persistent deficits for the processing of basic VP components when compared with TD children matched on chronological age and nonverbal reasoning abilities.

Cluster headache.

Cluster headache is an excruciating, strictly one-sided pain syndrome with attacks that last between 15 minutes and 180 minutes and that are accompanied by marked ipsilateral cranial autonomic symptoms, such as lacrimation and conjunctival injection. The pain is so severe that female patients describe each attack as worse than childbirth. The past decade has seen remarkable progress in the understanding of the pathophysiological background of cluster headache and has implicated the brain, particularly the hypothalamus, as the generator of both the pain and the autonomic symptoms.

Sunlight irradiance and habituation of visual evoked potentials in migraine: The environment makes its mark.

Background Migraine is a complex multifactorial disease that arises from the interaction between a genetic predisposition and an enabling environment. Habituation is considered as a fundamental adaptive behaviour of the nervous system that is often impaired in migraine populations. Given that migraineurs are hypersensitive to light, and that light deprivation is able to induce functional changes in the visual cortex recognizable through visual evoked potentials habituation testing, we hypothesized that regional sunlight irradiance levels could influence the results of visual evoked potentials habituation studies performed in different locations worldwide.