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Objective: To identify and disseminate research priorities for the headache field that should be areas of research focus during the next 10 years. Background: Establishing research priorities helps focus and synergize the work of headache investigators, allowing them to reach the most important research goals more efficiently and completely. Methods: The Headache Research Priorities organizing and executive committees and working group chairs led a multistakeholder and international group of experts to develop headache research priorities. The research priorities were developed and reviewed by clinicians, scientists, people with headache, representatives from headache organizations, health‐care industry representatives, and the public. Priorities were revised and finalized after receiving feedback from members of the research priorities working groups and after a public comment period. Results: Twenty‐five research priorities across eight categories were identified: human models, animal models, pathophysiology, diagnosis and management, treatment, inequities and disparities, research workforce development, and quality of life. The priorities address research models and methods, development and optimization of outcome measures and endpoints, pain and non‐pain symptoms of primary and secondary headaches, investigations into mechanisms underlying headache attacks and chronification of headache disorders, treatment optimization, research workforce recruitment, development, expansion, and support, and inequities and disparities in the headache field. The priorities are focused enough that they help to guide headache research and broad enough that they are widely applicable to multiple headache types and various research methods. Conclusions: These research priorities serve as guidance for headache investigators when planning their research studies and as benchmarks by which the headache field can measure its progress over time. These priorities will need updating as research goals are met and new priorities arise. Plain Language Summary: The American Headache Society led a large, international, multistakeholder process to identify headache research topics that should be prioritized during the next 10 years. With input from headache clinicians, scientists, people with headache, representatives from headache organizations, health‐care industry representatives, and the public, 25 research priorities within 8 categories were identified. These research priorities can help guide headache researchers when planning their studies and as benchmarks by which the headache field can measure its progress over time. [ABSTRACT FROM AUTHOR]

Objective: To provide a position statement update from The American Headache Society specifically regarding therapies targeting calcitonin gene‐related peptide (CGRP) for the prevention of migraine. Background: All migraine preventive therapies previously considered to be first‐line treatments were developed for other indications and adopted later for migraine. Adherence to these therapies is often poor due to issues with efficacy and tolerability. Multiple new migraine‐specific therapies have been developed based on a broad foundation of pre‐clinical and clinical evidence showing that CGRP plays a key role in the pathogenesis of migraine. These CGRP‐targeting therapies have had a transformational impact on the management of migraine but are still not widely considered to be first‐line approaches. Methods: Evidence regarding migraine preventive therapies including primary and secondary endpoints from randomized placebo‐controlled clinical trials, post hoc analyses and open‐label extensions of these trials, and prospective and retrospective observational studies were collected from a variety of sources including PubMed, Google Scholar, and ClinicalTrials.gov. The results and conclusions based upon these results were reviewed and discussed by the Board of Directors of The American Headache Society to confirm consistency with clinical experience and to achieve consensus. Results: The evidence for the efficacy, tolerability, and safety of CGRP‐targeting migraine preventive therapies (the monoclonal antibodies: erenumab, fremanezumab, galcanezumab, and eptinezumab, and the gepants: rimegepant and atogepant) is substantial, and vastly exceeds that for any other preventive treatment approach. The evidence remains consistent across different individual CGRP‐targeting treatments and is corroborated by extensive "real‐world" clinical experience. The data indicates that the efficacy and tolerability of CGRP‐targeting therapies are equal to or greater than those of previous first‐line therapies and that serious adverse events associated with CGRP‐targeting therapies are rare. Conclusion: The CGRP‐targeting therapies should be considered as a first‐line approach for migraine prevention along with previous first‐line treatments without a requirement for prior failure of other classes of migraine preventive treatment. [ABSTRACT FROM AUTHOR]

Objective: To determine if there are changes in structure and function of the retinal vasculature during and between migraine attacks using optical coherence tomography angiography (OCTA). Background: Migraine attacks commonly include visual symptoms, but the potential role of the retina in these symptoms is not well understood. OCTA is a rapid, non‐invasive imaging technique that is used to visualize the retinal microvasculature with high spatial resolution in a clinical setting. In this study we used OCTA to quantify different features of the retinal vasculature in patients with migraine during and between attacks, as well as in healthy controls (HCs). Methods: We performed a prospective cohort study of 37 patients with migraine with aura (MA) (median [interquartile range, IQR] age of 37 [14] years, 86% female) and 30 with migraine without aura (MO) (median [IQR] age of 37 [17] years, 77% female) and 20 HCs (median [IQR] age of 35 [7] years, 50% female). Macular OCTA scans were obtained for all participants for the interictal analysis. In 12 MA and eight MO, scans were captured both during and outside of migraine attacks and five HCs had initial and repeat scans. In addition to analyzing the morphology of the foveal avascular zone, we calculated the vessel flux index (VFI), which is an indicator of retinal perfusion and conventional metrics (such as vessel area density) in the foveal and parafoveal regions. Results: There was a significant difference in the parafoveal VFI in the ictal state between the groups (p = 0.009). During migraine attacks there was a significant reduction in the parafoveal region VFI in MA (−7%, 95% confidence interval [CI] −10% to −4%; p = 0.006) and MO (−7%, 95% CI −10% to −3%; p = 0.016) from their interictal baseline as compared to the change between repeat scans in HCs (2%, 95% CI −3% to 7%). Interictally, there was a mean (standard deviation [SD]) 13% (10%) (p = 0.003) lower blood perfusion in the MA group as compared to the MO group in the foveal region (mean [SD] 0.093 [0.023] vs. 0.107 [0.021], p = 0.003). Interictal analysis also revealed higher circularity in the superficial foveal avascular zone in the MA group compared with the MO group (mean [SD] 0.686 [0.088] vs. 0.629 [0.120], p = 0.004). In addition, interictal analysis of the patients with MA or MO and unilateral headache showed increased retinal vascular parameters consistent with greater perfusion in the eye ipsilateral to the side of the pain as compared with the contralateral eye. Conclusions: These results indicate that perfusion is reduced in MA and MO in the parafoveal retina during the ictal period. Interictally, the foveal retina in MA has reduced perfusion when compared to the foveal retina in MO. Patients with unilateral headache showed interictal asymmetry of retinal perfusion between eyes. These results indicate that changes in retinal perfusion could be a part of migraine pathophysiology, and that distinct retinal vascular signatures identified with OCTA could represent biomarkers for migraine. [ABSTRACT FROM AUTHOR]

Snowfall forecasting has historically been an area of difficulty for operational meteorologists, particularly in regions of complex terrain, such as the western United States. Attempts at improving forecasts have been made, but skill is still poor, with snowfall routinely overpredicted. A major reason for this overprediction has been the failure to accurately predict snow–liquid ratios (SLR) ahead of major events. This research proposes, develops, and tests multiple machine learning methods for dynamic SLR prediction for the Sky Islands of southeast Arizona by objectively comparing a multiple linear regression (MLR) against several more complex and flexible machine learning methods. Input parameters for each method were chosen based on variables found by previous studies to have a regression‐based relationship with SLR, with a focus on the lower mid‐levels of the troposphere. These parameters were also used to construct the MLR model, and its performance was compared objectively with the machine learning methods. When tested on historical events, a very high percentage of the network‐predicted SLR values fall within the margin of error of observed SLRs, which were calculated using gridded snow depth and snow water equivalent (SWE) data from the University of Arizona daily 4‐km SWE, SD, and SCE dataset (UASnow). A support vector machine (SVM), a k‐nearest neighbor (KNN) algorithm, and a random forest also showed high accuracies when tested on the dataset, and each showed a significant gain in skill compared with the MLR model, with skill being evaluated by multiple metrics. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to characterize the effects of the sleep‐wake cycle on neurovascular and behavioral characteristics of cortical spreading depression (CSD). Background: There is an important bi‐directional relationship between migraine and the sleep–wake cycle, but the basic mechanisms of this relationship are poorly understood. Methods: We have developed a minimally invasive microchip system to continuously monitor cerebral blood volume (CBV) with optical intrinsic signal (OIS), head movement, and multiple other physiological and behavioral parameters in freely behaving mice over weeks. Behavior is also monitored with simultaneous video recording. This system can also be used to intermittently trigger and record CSD and accompanying neurovascular and behavioral responses. CSD was triggered optically in different stages of the sleep–wake cycle. Results: The optical stimulus threshold to trigger CSD was significantly higher in the wake state compared to sleep (stimulation duration = 16.4 ± 9.7 s vs. 10.8 ± 5.8 s, p = 0.037, n = 6 mice). CSD evoked in the wake versus sleep state produced changes in CBV that were smaller (largest relative change –4.5 ± 5.0% ∆OIS vs. –14.3 ± 8.5% ∆OIS, p = 0.001) and shorter in duration (33:22 ± 6:37 vs. 49:42 ± 8:05 min:s, p = 0.012, n = 6 mice). The threshold for CSD and kinetics of associated CBV changes were correlated with the time since falling asleep or awakening (n = 47 CSDs in 6 mice). CSD triggered in the wake state was associated with a transient freezing behavior. CSD triggered during sleep typically caused a transient awakening and behavioral response. This was followed by a return to sleep until recovery from the sustained phase of decreased CBV that occurred 30–60 min later, at which time there was consistent awakening with behaviors similar to those that occurred at CSD onset. CSD triggered in the wake state evoked a transient decrease in heart rate (from 11.9 ± 0.8 to 9.6 ± 0.8 Hz, p = 0.002, n = 5), whereas when triggered in the sleep state there was a transient increase in HR (from 7.5 ± 0.4 Hz to 9.3 ± 1.1 Hz, p = 0.016, n = 5). Conclusions: The sleep–wake cycle has significant effects on CSD that may have relevance to the clinical presentations of migraine and brain injury. [ABSTRACT FROM AUTHOR]

The article discusses the changes in a wide variety of environmental and physiological parameters including sleep, exercise, and diet are also described as modulating inflammation. Topics include fundamental mechanism of nearly all physiological and pathological processes; and misuse of this terminology can distract from true understanding of disease mechanisms, and thereby delay progress in a field.

A minimally invasive, microchip‐based approach enables continuous long‐term recording of brain neurovascular activity, heart rate, and head movement in freely behaving rodents. This approach can also be used for transcranial optical triggering of cortical activity in mice expressing channelrhodopsin. The system uses optical intrinsic signal recording to measure cerebral blood volume, which under baseline conditions is correlated with spontaneous neuronal activity. The arterial pulse and breathing can be quantified as a component of the optical intrinsic signal. Multi‐directional head movement is measured simultaneously with a movement sensor. A separate movement tracking element through a camera enables precise mapping of overall movement within an enclosure. Data is processed by a dedicated single board computer, and streamed from multiple enclosures to a central server, enabling simultaneous remote monitoring and triggering in many subjects. One application of this system described here is the characterization of changes in of cerebral blood volume, heart rate and behaviour that occur with the sleep‐wake cycle over weeks. Another application is optical triggering and recording of cortical spreading depression (CSD), the slowly propagated wave of neurovascular activity that occurs in the setting of brain injury and migraine aura. The neurovascular features of CSD are remarkably different in the awake vs. anaesthetized state in the same mouse. With its capacity to continuously and synchronously record multiple types of physiological and behavioural data over extended time periods in combination with intermittent triggering of brain activity, this inexpensive method has the potential for widespread practical application in rodent research. Key points: Recording and triggering of brain activity in mice and rats has typically required breaching the skull, and experiments are often performed under anaesthesiaA minimally invasive microchip system enables continuous recording and triggering of neurovascular activity, and analysis of heart rate and behaviour in freely behaving rodents over weeksThis system can be used to characterize physiological and behavioural changes associated with the sleep‐wake cycle over extended time periodsThis approach can also be used with mice expressing channelrhodopsin to trigger and record cortical spreading depression (CSD) in freely behaving subjects. The neurovascular responses to CSD are remarkably different under anaesthesia compared with the awake state.The method is inexpensive and straightforward to employ at a relatively large scale. It enables translational investigation of a wide range of physiological and pathological conditions in rodent models of neurological and systemic diseases. [ABSTRACT FROM AUTHOR]

The article focuses on challenging the long-standing hypothesis that migraine aura directly initiates a migraine attack, presenting evidence that common brain mechanisms are activated before both migraine with aura and without aura attacks, indicating that aura is not the primary initiator of migraines and supporting the idea that both types of migraines share common underlying mechanisms.

Frequent or continuous headache, often refractory to medical therapy, is a common occurrence after head trauma. In addition to being the most common acute symptom after traumatic brain injury (TBI), headache is also one of the most persistent and disabling symptoms. Different studies indicate that 18‐58% of those suffering a TBI will have significant headache at 1 year following the trauma. In addition to being disabling on its own, posttraumatic headache (PTH) is a predictor of overall outcome after concussion. Despite its remarkable prevalence and associated social and economic costs, many fundamental and important questions about PTH remain unanswered. The purpose of this review is to identify key questions regarding the clinical characteristics of posttraumatic headache, its basic mechanisms, and its optimal management. We discuss phenotypic features of PTH, pathophysiological mechanisms of TBI including potential overlaps with those of migraine and other primary headache disorders, and potential novel targets for treatment. We suggest different strategies to finding answers to the questions regarding PTH in order to advance the understanding of the disorder and develop more effective therapies. [ABSTRACT FROM AUTHOR]

The braconid subfamily Euphorinae is a large, cosmopolitan group of endoparasitoid wasps. The majority of species attack adult hosts, a strategy that is rare among parasitic wasps, but there are also many species that attack nymphs and larval stages. Euphorine hosts may belong to a variety of insect orders (Coleoptera, Hemiptera, Hymenoptera, Neuroptera, Psocoptera, Orthoptera and Lepidoptera) although most euphorine tribes are confined to Coleoptera. Here we investigate the phylogenetic relationships of the Euphorinae based on molecular data (3 kb of nucleotide data from four markers: 18S, 28S, CAD and COI) and propose a higher-level classification based upon the resulting phylogeny. We also infer the evolution of host associations and discuss the diversification of the Euphorinae. Results from both Bayesian inference and maximum-likelihood analysis show that the subfamily, as previously circumscribed, is paraphyletic. We propose that the subfamily be expanded to include the tribes Meteorini and Planitorini ( Mannokeraia + Planitorus), so that it corresponds to a clade that is strongly supported as monophyletic in our analyses. Based on our results, a revised higher classification of the Euphorinae is proposed, in which 52 extant genera and 14 tribes are recognized. We reinstate the genus Microctonus belonging to the tribe Perilitini, and synonymize Ussuraridelus with Holdawayella, Sinuatophorus with Eucosmophorus. Furthermore, we propose the following tribal rearrangements: Spathicopis and Stenothremma are transferred to Perilitini; Tuberidelus, Eucosmophorus and Plynops to Cosmophorini; Ecclitura to Dinocampini; Chrysopophthorus, Holdawayella and Wesmaelia to Helorimorphini; Proclithroporus and Heia to Townesilitini. The monotypic tribe Cryptoxilonini is synonymized with Cosmophorini. The genera Pygostolus and Litostolus are placed in a separate tribe, Pygostolini, previously recognized as a subtribe among the Centistini. Parsimony-based ancestral state reconstructions suggest that the ancestor of Euphorinae was a parasitoid of lepidopteran larvae, and that a host shift to larval Coleoptera occurred only in one clade of the Meteorini, some members of which secondarily shifted back to larval lepidopteran hosts. In the remainder of the subfamily, there was an initial shift from larval to adult coleopterans, followed by subsequent shifts to adults or larvae of Hemiptera, Hymenoptera, Neuroptera, Orthoptera and Psocoptera. [ABSTRACT FROM AUTHOR]

Rudyard Kipling was determined to send his sickly, extremely near-sighted, son, Jack into the meat grinder that was World War I. His son was killed shortly after reaching the front. Kipling's readiness to sacrifice his son will be compared with Abraham's willingness to sacrifice his son, Isaac; both parents were willing to sacrifice their sons for a higher cause. How parents, especially combat veterans who may have been traumatized themselves, view military service will certainly influence how their sons resist or be prepared for military service. Is trauma passed from one generation to the next? Are parents willing to sacrifice their children? Oedipal families will view the prospect of child sacrifice differently than will Odyssean families. These antipodal perspectives will be contrasted as we follow how World War II combat vets prepared Vietnam era sons for service and combat. Composite voices are used to illustrate different vantage points. Tentative suggestions are offered for parents, their children and recruiters. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study investigated the effect of repetitive cortical spreading depression ( CSD) on behaviour and the anatomical and physiological patterns of cellular activation of cortical and subcortical areas in awake, moving rats. Rat behaviours in response to repetitive CSD events evoked by the application of KCl were quantified with electrophysiological recording. Immunohistochemistry was used to quantify anatomical regions of cellular activation. The effects of acute valproic acid administration on the behavioural parameters and cellular activation were evaluated. CSD significantly decreased locomotor activity and induced freezing in awake, moving rats, and stimulated c-Fos expression in the cortex, trigeminal nucleus caudalis ( TNC), and amygdala. CSD also resulted in a prominent increase in c-Fos expression in the ipsilateral thalamic reticular nucleus ( TRN) visual sector. Electrophysiological recordings revealed propagation of CSD into the TRN. Valproic acid pretreatment decreased the duration of CSD-induced freezing episodes and reversed the CSD-induced reduction in locomotor activity. Acute valproic acid administration also significantly blocked CSD-induced c-Fos expression in the TNC and TRN. These findings show that CSD events cause consistent behavioural responses and activate specific brain regions in awake, freely moving rats. Selective activation of TRN by CSD and the suppression of this activation by valproic acid suggest that this brain region may play an important role in migraine pathogenesis and may represent a novel target for migraine therapy. [ABSTRACT FROM AUTHOR]

Background and Purpose: Migraine is an extraordinarily common brain disorder for which treatment options continue to be limited. Agonists that activate the δ-opioid receptor may be promising for the treatment of migraine as they are highly effective for the treatment of chronic rather than acute pain, do not induce hyperalgesia, have low abuse potential and have anxiolytic and antidepressant properties. The aim of this study was to investigate the therapeutic potential of δ-opioid receptor agonists for migraine by characterizing their effects in mouse migraine models.Experimental Approach: Mechanical hypersensitivity was assessed in mice treated with acute and chronic doses of nitroglycerin (NTG), a known human migraine trigger. Conditioned place aversion to NTG was also measured as a model of migraine-associated negative affect. In addition, we assessed evoked cortical spreading depression (CSD), an established model of migraine aura, in a thinned skull preparation.Key Results: NTG evoked acute and chronic mechanical and thermal hyperalgesia in mice, as well as conditioned place aversion. Three different δ-opioid receptor agonists, SNC80, ARM390 and JNJ20788560, significantly reduced NTG-evoked hyperalgesia. SNC80 also abolished NTG-induced conditioned place aversion, suggesting that δ-opioid receptor activation may also alleviate the negative emotional state associated with migraine. We also found that SNC80 significantly attenuated CSD, a model that is considered predictive of migraine preventive therapies.Conclusions and Implications: These data show that δ-opioid receptor agonists modulate multiple basic mechanisms associated with migraine, indicating that δ-opioid receptors are a promising therapeutic target for this disorder. [ABSTRACT FROM AUTHOR]

The cervical nerves may play a significant role in primary headache disorders. We reviewed the patterns of pain evoked by stimulation of the first 3 cervical nerves (C1-C3) in 10 patients with chronic occipital pain, 6 of whom also had migraine. Stimulation at the C1 level evoked periorbital and frontal pain in 6 of 6 patients with migraine but evoked occipital or cervical pain in those without migraine. C2 and C3 stimulation resulted in occipital or cervical pain in all patients. The C1 nerve may have an important sensory function in headache disorders that have orbital and frontal pain as a prominent feature. Ann Neurol 2013;74:145-148 [ABSTRACT FROM AUTHOR]

A migraine attack is an extraordinarily complex brain event that takes place over hours to days. This review focuses on recent human studies that shed light on the evolution of a migraine attack. It begins with a constellation of premonitory symptoms that are associated with activation of the hypothalamus and may involve the neurotransmitter dopamine. Even in the premonitory phase, patients experience sensitivity to sensory stimuli, indicating that central sensitization is a primary phenomenon. The migraine attack progresses to a phase that in some patients includes aura, which involves changes in cortical function, blood flow, and neurovascular coupling. The aura phase overlaps with the headache phase, which is associated with further changes in blood flow and function of the brainstem, thalamus, hypothalamus, and cortex. Serotonin receptors, nitric oxide, calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide, and prostanoids are demonstrated specific chemical mediators of migraine based on therapeutic and triggered migraine studies. A number of migraine symptoms persist beyond resolution of headache into a postdromal phase, accompanied by persistent blood flow changes in several brain regions. Although these phases of migraine have substantial temporal, neurochemical, and anatomical overlap, each represents an important window onto the pathophysiology of migraine as well as a target for therapeutic intervention. A comprehensive approach to migraine requires an understanding of the entire range of mechanisms and resultant symptoms that occur throughout the evolution of an attack. [ABSTRACT FROM AUTHOR]

The article compares the natural sleep of patients with obstructive sleep apnea (OSA) and midazolam sedation sleep endoscopy with bispectral analysis (BIS), a signal-processing technique providing interpretation of the electroencephalogram (EEG). It reports that the midazolam sedation sleep endoscopy better identifies the obstruction sites and tissue collapsibility and concludes the sleep endoscopy safely evaluates the potential surgical patients.

Objectives.- To develop a translational mouse model for the study and measurement of non-evoked pain in the orofacial region by establishing markers of nociceptive-specific grooming behaviors in the mouse. Background.- Some of the most prevalent and debilitating conditions involve pain in the trigeminal distribution. Although there are current therapies for these pain conditions, for many patients, they are far from optimal. Understanding the pathophysiology of pain disorders arising from structures innervated by the trigeminal nerve is still limited, and most animal behavioral models focus on the measurement of evoked pain. In patients, spontaneous (non-evoked) pain responses provide a more accurate representation of the pain experience than do responses that are evoked by an artificial stimulus. Therefore, the development of animal models that measure spontaneous nociceptive behaviors may provide a significant translational tool for a better understanding of pain neurobiology. Methods.- C57BL/6 mice received either an injection of 0.9% saline solution or complete Freund's adjuvant into the right masseter muscle. Animals were video-recorded and then analyzed by an observer blind to the experiment group. The duration of different facial grooming patterns performed in the area of injection were measured. After 2 hours, mice were euthanized and perfused, and the brainstem was removed. Fos protein expression in the trigeminal nucleus caudalis was quantified using immunohistochemistry to investigate nociceptive-specific neuronal activation. A separate group of animals was treated with morphine sulfate to determine the nociceptive-specific nature of their behaviors. Results.- We characterized and quantified 3 distinct patterns of acute grooming behaviors: forepaw rubbing, lower lip skin/cheek rubbing against enclosure floor, and hindpaw scratching. These behaviors occurred with a reproducible frequency and time course, and were inhibited by the analgesic morphine. Complete Freund's adjuvant-injected animals also showed Fos labeling consistent with neuronal activation in nociceptive-specific pathways of the trigeminal nucleus after 2 hours. Conclusions.- These behaviors and their correlated cellular responses represent a model of trigeminal pain that can be used to better understand basic mechanisms of orofacial pain and identify new therapeutic approaches to this common and challenging condition. [ABSTRACT FROM AUTHOR]

The tribe Maxfischeriini, previously placed in Helconinae, is emended to subfamily status based on morphological and biological evidence. Proposed autapomorphies for Maxfischeriinae include: the presence of a pronotal shelf, forewing vein 1a and 2a present, although 1a nebulous, ventral valve of the ovipositor with serrations from tip to base and specialized egg morphology. The novel, pedunculate egg morphology is described for Maxfischeria, representing a new life-history strategy among Braconidae. Based on egg and ovipositor morphology, we suggest that Maxfischeria is a proovigenic, koinobiont ectoparasitoid. Five new species of Maxfischeria Papp are described with an illustrated key to all species ( Maxfischeria ameliae, Maxfischeria anic, Maxfischeria briggsi, Maxfischeria folkertsorum and Maxfischeria ovumancora). In addition to the identification key presented here, all known species of Maxfischeria can be separated using the barcoding region of cytochrome c oxidase subunit I ( COI). Based on molecular data, the phylogenetic relationships among the six known species of Maxfischeria are as follows: ( M. folkertsorum ( M. ovumancora ( M. briggsi ( M. anic ( M. tricolor + M. ameliae))))). [ABSTRACT FROM AUTHOR]

Objective: To validate the locally developed surgical inpatient satisfaction instrument (SIPS) across a diverse population of perioperative patients and to identify independent contributors to patient satisfaction. Methods: Patients over 18 years of age who had undergone surgery either as a day or inpatient in three public hospitals within the eastern area of the New Territories in Hong Kong were recruited prior to discharge. Seven hundred and sixty-five patients completed our 40-item seven-factor surgical patient satisfaction instrument along with an existing European measure of inpatient satisfaction in cancer patients (EORTC In-Pats 32). Analysis included factorial validity by exploratory factor analyses, unidimensionality, item fit, differential item functioning and concurrent validity. Univariate and linear logistic regression analysis of overall satisfaction was carried out. Results: Psychometric testing demonstrated the instrument to be robust and generalizable and did not support removal of any of the items. The independent predictor of overall surgical inpatient satisfaction was the quality of nursing care and age over 50 years. Satisfaction was not confounded by gender, length of hospital stay or educational level. Conclusions: SIPS was shown to be valid across a range of surgical procedures. [ABSTRACT FROM AUTHOR]

Migraine continues to be an elephant in the room of medicine: massively common and a heavy burden on patients and their healthcare providers, yet the recipient of relatively little attention for research, education, and clinical resources. Its visibility is gradually increasing, however, as advances in genetics, imaging, epidemiology, and pharmacology produce a more definitive understanding of the condition, and identify more specific and effective treatments. Rapid evolution of concepts regarding its prevalence, pathophysiology, and clinical management is leading to growing recognition of migraine as a fundamentally important disorder of the nervous system. Ann Neurol 2009;65:491-498 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To evaluate diagnostic reliability of contact rhinoscopy in patients with nasopharyngeal carcinoma. Study Design: A cross-sectional randomized single-blinded study was carried out to evaluate the reliability of the findings of contact rhinoscopy in patients with nasopharyngeal carcinoma assessed by different observers. Methods: Random images of contact endoscopy of 157 subjects including normal patients and patients with nasopharyngeal carcinoma, both prior to external beam radiation therapy (RT), the non-RT group, and after external beam radiation therapy, the post-RT group, were available for analysis. Three independent observers of varying clinical experience and histopathologic knowledge viewed the images and made a diagnosis for each image. The diagnosis of each image was correlated with the histology of the biopsy from the corresponding patient. Results: In the non-RT group, Kappa values for inter- and intraobserver reliability to differentiate normal epithelium from primary nasopharyngeal carcinoma were 0.894, 1.000, 0.794 and 0.694, 1.000, 0.776 for the house officer, radiologist, and pathologist, respectively. There were no significant differences in interobserver and intraobserver reliabilities between the assessors. In the post-RT group, Kappa values for the inter- and intraobserver reliability to diagnose recurrent carcinoma or atypia, squamous metaplasia, and radiation change for the three observers were 0.820, 0.718, 0.775 and 0.731, 0.622, 0.734, respectively. There were no significant differences in interobserver and intraobserver reliabilities between the assessors. Conclusions: The clinical diagnosis of nasopharyngeal carcinoma by contact endoscopy is highly reliable and is not dependent on the clinical experience or knowledge of histopathology of the observers. Laryngoscope, 119:523-527, 2009 [ABSTRACT FROM AUTHOR]

There is accumulating evidence of a neurogenic basis of migraine. This evidence arises from both the clinical and experimental domains. Many of the well known clinical features of migraine attacks including the prodrome are not explained by changes in vascular caliber. Despite the fact that ergotamines and triptans are vasoactive does not provide substantive proof that vasoconstriction is their most important mechanism of action. Several effective treatments for migraine, both old and new, do not affect vascular caliber. Experimental evidence from investigation of both the aura and headache phases of migraine clearly supports a neural basis of migraine. All genes thus far conclusively associated with hemiplegic migraine code for neural proteins. [ABSTRACT FROM AUTHOR]

Neurotransmitters and their receptors have been involved in both proper brain development and neurodevelopmental disorders. The role that nicotinic receptors play in immature cortical neurons was initially investigated by gene profiling using Affymetrix DNA arrays. Both short (15 min) and prolonged (18 h) treatments with nicotine did not induce modification in gene expression, whereas a significant down-regulation of c-fos protein levels was observed after 18 h treatment. Conversely, a brief treatment with the glutamatergic agonist NMDA triggered up-regulation of immediate early genes and transcription factors, which remained unaffected by pre-treatment for 18 h with nicotine. Calcium imaging studies revealed that NMDA activated a sustained increase in intracellular calcium concentration in the majority of neurons, whereas nicotine evoked only a transient calcium increase in a smaller percentage of neurons, suggesting that the calcium signalling response was correlated with activation of gene expression. Nicotine effects on immature cortical neurons perhaps do not require gene regulation but may be still acting on signalling pathways. [ABSTRACT FROM AUTHOR]

Background. Nasopharyngeal dysplasia or nasopharyngeal carcinoma in situ (NPCIS) lesions have rarely been reported. Timely diagnosis of the preinvasive lesion may improve prognosis. Contact endoscopy has been documented to accurately differentiate normal cells of the nasopharynx from malignant cells and allows a real-time diagnosis of primary and recurrent nasopharyngeal carcinoma (NPC) in a clinical setting. However, the role of contact endoscopy in the diagnosis of NPCIS is unknown. Methods. The superficial cells of the nasopharynx in a patient with NPCIS were examined in vivo under local anaesthesia by use of a contact rhinoscope. The contact endoscopic findings were correlated with the histologic findings of the biopsy. Results. The atypical cells of the lesion were magnified and visualized under contact endoscopy. Histopathologic analysis of the biopsied tissue confirmed the presence of NPCIS staining positively for Epstein-Barr virus (EBV)–encoded RNA (EBER). No cell-free EBV DNA was detected in the sera of the patient. Conclusions. Contact endoscopy can accurately identify the atypical cells of a tiny preinvasive lesion in the nasopharynx in a clinical setting, which may not be evident in routine imaging examination. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX–XXX, 2005 [ABSTRACT FROM AUTHOR]

The neuroprotective drug riluzole has multiple effects on cellular signaling. We found that riluzole rapidly and reversibly inhibited spontaneous Ca2+ oscillations in both immortalized GnRH-secreting hypothalamic neurons (GT1 cells) and in the prolactin and growth-hormone-secreting GH3 cell line. At lower concentrations (100 nm-5 microM), riluzole reduced the amplitude and frequency of spontaneous Ca2+ oscillations, whereas at higher concentrations it abolished spontaneous Ca2+ signaling. Whole-cell current clamp recordings in GH3 cells revealed that riluzole decreased the action potential frequency, amplitude, and duration. Riluzole inhibited voltage-gated Na+ currents, increased iberiotoxin-sensitive voltage-gated K+ currents, and had no effect on voltage-gated Ca2+ currents in GH3 cells. Riluzole also inhibited voltage-gated Na+ currents and increased voltage-gated K+ channels in GT1 cells. The inhibitory effects of riluzole on Ca2+ signaling were blocked by pretreatment with iberiotoxin in GH3 cells, but only partially reduced by iberiotoxin in GT1 cells. These results indicate that riluzole inhibits Ca2+ signaling primarily by activation of K+ channels in GH3 cells, and also by inhibition of Na+ channels in GT1 cells. Riluzole's inhibition of spontaneous excitability and Ca2+ signaling may be involved in its multiple effects on cellular function in the nervous system. [ABSTRACT FROM AUTHOR]

Objective To evaluate the potential use of contact endoscopy for the diagnosis of persistent and recurrent nasopharyngeal carcinoma in postirradiated patients. Study Design Prospective study to examine 64 consecutive patients who have been irradiated for nasopharyngeal carcinoma in a clinic setting using contact rhinoscopes (Karl Storz, Tuttlingen, Germany [7215 AA, 0°, and 7215 BA, 30°; 23 cm long. 4 mm in diameter]). Methods The superficial cells of the posterior walls of the nasopharynx were stained with 1% methylene blue and examined with contact rhinoscopes with the patient under local anesthesia at high magnifications (×60 and ×150). Biopsy of the areas under examination was performed. The contact endoscopic images were analyzed and correlated with the corresponding histological sections of the biopsy tissues. Results Contact endoscopy was performed in 64 patients (54 men; mean age, 42 y) with the use of local anesthesia. Four patterns of contact endoscopic findings were identified: squamous metaplasia (43 cases), postirradiation atypia (10), granulation tissue (6), and malignancy (5). In the last group, the nasopharynx appeared normal in two patients (40%). The findings of contact endoscopy correlated well with the histological findings (kappa reliability coefficient = 0.847; P <.001; diagnostic accuracy, 92.1%). For prediction of persistent and recurrent disease, the sensitivity and specificity of endoscopic findings were both 100%. Conclusion Contact endoscopy is an accurate, reliable office-based procedure that allows for in vivo and in situ diagnosis of persistent and recurrent nasopharyngeal carcinoma in postirradiated patients. [ABSTRACT FROM AUTHOR]

Objective: To describe a combined transoral and transnasal approach power-assisted endoscopic adenoidectomy by StraightShot® microdebrider and Endoscrub ® device in children. Method: Transoral power-assisted endoscopic adenoidectomy using a 45°-curved cutting visor of a StraightShot® microdebrider (Medtronic Xomed, Jacksonville, FL, USA) is performed with an Endoscrub, irrigation device (Medtronic Xomed) attached to the rigid endoscope. The oscillating mode (1500 r.p.m.) of the microdebrider is selected. The dissection begins at the inferior pole of the adenoids and swifted upwards to the roof of the nasopharynx. Transnasal dissection of the choanal extension of the adenoids is achieved using a straight-cutting visor with the aid of a 0° rigid endoscope. Results: The technique was performed in 11 consecutive patients (six male and five female) in a 6-month period. The mean age of the patients was 6.9 years (range, 3–9 years). The main indication for surgery was obstructive sleep apnoea with huge obstructive adenoids and with choanal extension. The mean operative time was 4.8 min (range, 2–11 min). The mean blood loss was 12.8 mL (range, 4–16 mL). No intraoperative or postoperative complications were recorded. Conclusion: The described technique for dissection of adenoids in children is safe and is recommended for patients with large adenoids and with choanal extension. Chinese Abstract. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the potential use of contact endoscopy for the diagnosis of nasopharyngeal carcinoma (NPC). Study Design Prospective study to examine the nasopharynx of 30 patients with nasopharyngeal carcinoma and 18 subjects with normal nasopharynx in a clinic setting using contact rhinoscopes (Karl Storz, Tuttlingen, Germany, 7215 AA, 00 and 7215 BA, 300; 23 cm long; 4 mm in diameter). Methods The superficial cells of the normal nasopharynx and the nasopharyngeal tumors were stained with 1% methylene blue and examined with contact rhinoscopes at high magnifications (×60 and ×150). The areas under examination were then biopsied. The contact endoscopic images were compared with the corresponding hematoxylin and eosin-stained histologic sections of the biopsied tissues. Results Sixty-six procedures were performed in 48 patients. The images of normal pseudostratified ciliated epithelium and squamous epithelium were readily recognized by contact endoscopy in all subjects with normal nasopharynx (10 men and 8 women; mean age, 51.9 y). Twenty-six of 30 patients with NPC (86.6%; 18 men and 8 women; mean age, 50.6 y) were successfully examined by contact endoscopy under local anesthesia. In these 26 patients, two patterns of malignant cells were identified with contact endoscopy. The patterns of contact endoscopic images corresponded well with the histologic findings. Conclusion Contact endoscopy is an accurate and reliable office-based procedure, which allows for in-vivo diagnosis of nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Objectives To determine objective data to improve the methods of identification of the anterior ethmoidal artery during endoscopic dissection. Study Design Cadaveric dissection of adult human heads. Methods A 0°, 4-mm rigid endoscope was used to guide uncinectomy and frontoethmoidectomy. The location of the anterior ethmoidal artery was first determined visually and then confirmed by passing a needle through the anterior ethmoidal foramen from the orbit into the nose in all cases. The distances were endoscopically measured using a simple ruler between two nasal landmarks and the anterior ethmoidal artery. Results Fifty-six nasal fossae in 28 cadavers were dissected endoscopically. The median distance between the artery and the 'axilla' formed by the anterior attachment of the middle turbinate to the lateral nasal wall was 20 mm (range, 17-25 mm), irrespective of the side. The measurement differed by less than 2 mm between the sides in the same individual. The median distance between the artery and the 'axilla' formed by the medial and lateral crura of the lower lateral cartilage (superomedial edge of the nostril) was 62 mm (range, 55-75 mm) for both sides. The artery was found to be in direct alignment with the two 'axillae' formed by the middle turbinate and the nostril edge. Conclusions The distance between the ethmoidal artery and the axilla of the middle turbinate showed the least intraindividual and interindividual variations. The tip of the endoscope (or the ruler) points directly at the anterior ethmoidal artery in the fovea ethmoidalis when its edge is aligned with the two nasal landmarks. These simple guidelines can aid the identification of the artery in endoscopic frontoethmoidectomy. [ABSTRACT FROM AUTHOR]

Cyclicity has been noted as a key feature of Mayan conceptions of time and space from the Classic period (A.D. 250-900) to the present. Similarly, pattern of repetition and cyclicity have been noted as characteristic of Mayan discourse structure. In this article cyclicity in worldview and in discourse structure is examined in Itzaj Maya narrative, with emphasis on the importance of the schema of the sun's journey to both. [ABSTRACT FROM AUTHOR]

The article ponders on the link between cortical spreading depression (CSD) and migraine. CSD has been thought to be the brain mechanism that underlies migraine aura. However, despite the presence of causative link between CSD and migraine attack, questions still remain on the role of CSD in the initiation of migraine attack. The author argues that investigation on CSD can offer relevant information on the basic mechanisms of migraine.

Objectives To compare the long-term recurrence rate of the standard technique (simple sinectomy) and the supra-auricular approach (wide local excision) for the surgical management of preauricular sinuses. Study Design Retrospective cohort. Methods Fifty-four patients with a preauricular sinus excised between May 1986 and December 1996 were included in this study. All patients were categorized into one of two groups based on the type of surgery performed: the standard technique or the supra-auricular approach. The medical records were then reviewed and the latest information concerning the recurrence of a preauricular sinus were updated by phone interview. The recurrence rate of these two groups was statistically analyzed by the Fisher exact test. Results Forty-nine of 54 patients were successfully contacted with data updated and analyzed. The 32% recurrence rate of the standard excision (n = 25) was significantly higher than the 3.7% recurrence rate of the supra-auricular approach (n = 27; two-tailed test, P = .01). Conclusion The supra-auricular approach for excision of a preauricular sinus has a statistically lower recurrence rate in comparison to the standard technique. [ABSTRACT FROM AUTHOR]