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Comparator selection is an important consideration in the design of observational research studies that evaluate potential associations between drug therapies and adverse event risks. It can affect the validity of observational study results, and potentially impact data interpretation, regulatory decision making, and patient medication access.The aim of this study was to assess the impact of comparator selection bias using two real-world case studies evaluating an increased rate of acute myocardial infarction (AMI).Data from the Truven Health Analytics MarketScanNo significant association between TRT and AMI was observed among TRT-treated (N = 198,528, mean age 52.4 ± 11.4 years) versus PDE5i-treated men (N = 198,528, mean age 52.3 ± 11.5 years) overall (adjusted hazard ratio [aHR] 1.01; 95% CI 0.95-1.07; p = 0.80). Among patients with prior cardiovascular disease (CVD), risk of AMI was significantly increased for TRT-treated versus PDE5i-treated patients (aHR 1.13; 95% CI 1.03-1.25). The triptan study included three comparisons (triptans [N = 436,642] vs prescription NSAIDs [N = 334,152], opiates [N = 55,234], and untreated migraine [N = 1,168,212]), and a positive control (untreated vs general non-migraine patients [N = 11,735,009]). Analyses of MI risk in migraine patients prescribed triptans versus NSAIDs/opiates had mixed results: the point estimate ranged from 0.33 to 0.84 depending on chosen study window.Cardiovascular outcomes were not worse in hypogonadism patients with TRT versus PDE5i; however, a potential association with AMI was found in patients with prior CVD receiving TRT versus PDE5i. Findings pointed to a pseudo-protective effect of triptans versus untreated migraine patients or those potentially older and less healthy patients exposed to prescription NSAIDs or opiates. Triptan users should not be compared with those using other anti-migraine prescriptions when evaluating cardiovascular outcomes in migraine patients. Presence of high cardiovascular risks may contribute to channeling bias-healthier subjects being selected to receive treatment-highlighting the importance of choosing comparators wisely in observational studies.

X-ray photoelectron spectroscopy analysis was applied to investigate the thermal stability under ultra-high vacuum environment of the surface oxide film formed by electrochemical passivation of a newly-designed Cr15Fe10Co5Ni60Mo10 (at. %) multi-principal element alloy and providing the alloy superior localized corrosion resistance compared to conventional stainless steels and alloys. A spectral decomposition methodology involving the subtraction of Auger peaks overlapping the Fe2p and Co2p core level regions was applied for quantification of the oxide film composition and thickness. The results show that, at 100 °C, the passive oxide film is mainly dehydrated and dehydroxylated. Obvious loss of Ni hydroxide and conversion of Mo(VI) to Mo(IV) species are observed at 200 °C, with further reduction of Mo species to Mo(III) observed at 300 °C. In this temperature range, the total cation quantity in the oxide film remains stable despite the compositional alteration. At 400 °C, Cr(III) oxide forms at the expense of Fe and Mo oxides, resulting in an oxide film essentially consisting of chromium oxide. At 500 °C, Cr(III) oxide is eliminated, making the passive film unstable at this temperature. Possible Cr oxide removal mechanisms are discussed.

International audience; The adsorption of 2-MBT organic inhibitor on copper and its effects on anodic oxide growth in NaOH were investigated using cyclic voltammetry, X-ray photoelectron spectroscopy, and time-of-flight secondary ion mass spectrometry techniques. It is shown that 2-MBT significantly impedes the growth of the Cu(I) oxide by forming a multilayered organic film on the surface. A major factor influencing the formation and properties of the organic barrier layer is the presence and structure of the interfacial native oxide on which it forms. The 2-MBT multilayer bonds to the metallic copper substrate mostly via its sulphur atoms along with a small fraction of the nitrogen atoms also bonding to the metallic substrate. Additionally, there is an interaction between the inhibitor molecules and copper released from the surface to form metal-organic complexes in the outer layers of the thicker films.

Surface analysis by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry was applied to investigate the origin of the enhanced surface passivity and resistance to a chloride-induced breakdown provided by the protective ultrathin oxide films formed on Cr–Fe–Co–Ni–Mo single-phase fcc multi-principal element alloys. A bilayer structure of the oxide films is observed with the inner barrier layer mostly constituted of Cr(III) oxide and the outer layer enriched in Cr(III) hydroxides and Mo(IV,VI) oxides. The Mo(VI) and Mo(IV) species are mainly located in the outer and inner parts of the outer layer, respectively. Anodic passivation promotes mainly the growth of the inner layer on the alloy of higher Cr bulk content and the outer layer on the alloy of higher Mo bulk content. Passivation also promotes the enrichment of Cr(III) hydroxide and Mo(IV) and Mo(VI) oxides in the outer layer. Depth distribution analysis suggests that the ultra-thin protective inner barrier contains Cr(III)-depleted heterogeneities acting as weak sites for chloride attack, which are reinforced by the Mo(IV) oxide species concentrated close to the inner barrier layer. This elemental distribution provides an explanation for the reinforcement of the resistance to localized corrosion observed on these Cr–Fe–Co–Ni–Mo alloys.

International audience; Electrochemistry along with advanced surface analyses (X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry) were implemented to investigate copper corrosion inhibition by 2-mercaptobenzothiazole (2-MBT) in hydrochloric aqueous solution and the effects of electrochemical control on the formation of the inhibiting interface. It is shown that reducing the native surface oxide by cathodic reduction prior to exposure to the inhibitor drastically decreases the rate of anodic dissolution. Additionally, increasing the exposure time of the metal surface to the inhibitor results in even better protection against dissolution. 2-MBT adsorbs as multilayers and bonds to both metallic copper and residual copper oxide islands via its sulphur atoms. Partial dissociation of the molecule, releasing the exocyclic sulphur, which then bonds to metallic Cu, is observed. Further dissociation of the molecule, releasing the endocyclic sulphur, is induced by anodic polarization, forming defects in the organic layer and thus compromising the barrier properties of the organic layer.

International audience; The mechanisms of initial oxide growth on the equiatomic CoCrFeMnNi high entropy alloy were studied in situ by X-ray photoelectron spectroscopy on clean, oxide-free surfaces exposed stepwise to low-pressure gaseous oxygen. Cr(III), Mn(III), Fe(III), Co(II) but no Ni(II) oxides were formed at 100 °C, and Mn(II) at 200 °C. Data quantification revealed a transition mechanism from selective initial oxidation to 3D kinetically-controlled growth, leading to stratification of the oxide film. Formation of the Co-rich outer layer above the Cr-rich inner layer first formed implies predominant cationic outward oxide growth supported by the overall stoichiometry of the film.

Migraine is a highly prevalent neurological disease of varying attack frequency. Headache attacks that are accompanied by a combination of impact on daily activities, photophobia and/or nausea are most commonly migraine. The headache phase of a migraine attack has attracted more research, assessment tools and treatment goals than any other feature, characteristic, or phase of migraine. However, the migraine attack may encompass up to 4 phases: the prodrome, aura, headache phase and postdrome. There is growing recognition that the burden of migraine, including symptoms associated with the headache phase of the attack, may persist between migraine attacks, sometimes referred to as the “interictal phase.” These include allodynia, hypersensitivity, photophobia, phonophobia, osmophobia, visual/vestibular disturbances and motion sickness. Subtle interictal clinical manifestations and a patient's trepidation to make plans or commitments due to the unpredictability of migraine attacks may contribute to poorer quality of life. However, there are only a few tools available to assess the interictal burden. Herein, we examine the recent advances in the recognition, description, and assessment of the interictal burden of migraine. We also highlight the value in patients feeling comfortable discussing the symptoms and overall burden of migraine when discussing migraine treatment needs with their provider.

International audience; We report on a new technique to form and seal micro-fabricated cells. The technique consists in integrating single-use sealing structures actuated through laser irradiation, either to isolate cavities from each other or to connect them. Inspired by the glass-blowing techniques, we demonstrate “make-seals” and “break-seals” cells. This technique opens new

Background Perimenstrual migraine attacks in women with menstrual migraine is difficult to treat. This post-hoc analysis evaluated the efficacy of lasmiditan, a high affinity and selective 5-HT1F receptor agonist, for perimenstrual attacks. Methods Patients from two randomized, double-blind, placebo-controlled clinical trials (MONONOFU and CENTURION) were instructed to treat an attack with a single dose of study medication within four hours of pain onset. After dosing, the proportion of patients who achieved freedom from migraine-related head pain, most bothersome symptom, and disability was reported at baseline up to 48 hours after dose and pooled data were evaluated. Results A total of 303 patients (MONONOFU N = 78; CENTURION N = 225) treated perimenstrual migraine attacks with lasmiditan 50 mg (N = 24), 100 mg (N = 90), 200 mg (N = 110), and placebo (N = 79). More patients achieved migraine-related head pain freedom with lasmiditan 200 mg versus placebo at all time points assessed. At 2 hours, 33.6% of patients in the 200-mg group (p Conclusions Lasmiditan treatment of perimenstrual migraine attacks was associated with freedom from migraine-related head pain at two hours, early onset of efficacy, and sustained efficacy. Clinical Trial registration: NCT03962738 and NCT03670810

International audience; Nous présentons en premier lieu des travaux visant au développement d’horloges atomiques microondes à microcellule de haute stabilité, basées sur le phénomène de piégeage cohérent de population (CPT). Nous démontrons l’implémentation de séquences d’interrogation impulsionnelles avancées permettant une réduction drastique des effets de déplacement lumineux, combinés à la poursuite d’efforts technologiques pour l’aboutissement d’une technologie de microcellule avancée. En second lieu, nous démontrons des références de fréquence optiques, lasers stabilisés sur microcellule par spectroscopie sub-Doppler bi-fréquence, présentant une stabilité relative de fréquence court terme de 1.5 10-12 à 1 s, 100 fois supérieure à celle des micro-horloges atomiques commerciales actuelles.

To evaluate the efficacy of lasmiditan (LTN) in treating migraine attacks of mild vs. moderate or severe pain intensity.Pooled data from two single-attack, placebo-controlled studies (SAMURAI [NCT02439320] and SPARTAN [NCT02605174]), and a prospective, randomized, open-label study (GLADIATOR [NCT02565186]) were assessed. Efficacy measures included the proportion of attacks with 2-h pain freedom (PF), 2-h most bothersome symptom (MBS) freedom, and 24-h sustained pain freedom (SPF). Fisher's exact test was used to compare the proportion of PF, SPF, or MBS freedom outcomes among attacks treated at mild, moderate, or severe pain.In SAMURAI and SPARTAN, most treated attacks were of moderate (Data from two placebo-controlled, single-attack trials, and an open-label study including treatment of multiple attacks, suggested a tendency to relatively better efficacy outcomes when LTN treatment was initiated at mild vs. moderate to severe pain. Further research is needed to better understand the relationship of lasmiditan outcomes to the time of administration in the course of a migraine attack.

Atomic devices such as atomic clocks and optically-pumped magnetometers rely on the interrogation of atoms contained in a cell whose inner content has to meet high standards of purity and accuracy. Glass-blowing techniques and craftsmanship have evolved over many decades to achieve such standards in macroscopic vapor cells. With the emergence of chip-scale atomic devices, the need for miniaturization and mass fabrication has led to the adoption of microfabrication techniques to make millimeter-scale vapor cells. However, many shortcomings remain and no process has been able to match the quality and versatility of glass-blown cells. Here, we introduce a novel approach to structure, fill and seal microfabricated vapor cells inspired from the century-old approach of glass-blowing. In particular we demonstrate opening and closing single-use zero-leak microfabricated valves, actuated exclusively by laser, and operating in the same way as the "make-seals" and "break-seals" found in the filling apparatus of traditional cells. Such structures are employed to fill cesium vapor cells at the wafer-level. The make-seal structure consists of a glass membrane that can be locally heated and deflected to seal a microchannel. The break-seal is obtained by breaching a silicon wall between cavities. This new approach allows adapting processes previously restricted to glass-blown cells. It can also be extended to vacuum microelectronics and vacuum-packaging of micro-electro-mechanical systems (MEMS) devices., 13 pages, 6 figures

International audience; We report on a new technique to form and seal microfabricated cells that alleviates some of the limitations imposed by current solutions. The technique consists in integrating single-use sealing structures that can be actuated through laser irradiation, either to isolate cavities from each other or to connect them. Inspired by the well-established glass-blowing techniques, it reproduces on a wafer the “make-seal” and “break-seal” features found in conventional cell filling setups. By allowing cells to be evacuated, filled and sealed after having been fully-formed, this technique opens new venues for atomic devices. Here, we demonstrate both features and present one use case where alkali dispensers are used in association with non-noble gasses despite their gettering ability.

The vast composition space of the Cr-Fe-Co-Ni-Mo system was explored by massive thermodynamic calculations in order to design and characterize multi-component single-phase fcc alloys optimized in Cr and Mo content and having enhanced passivity. Adding up to 15 at.% Mo while retaining the fcc single-phase is possible, which is unprecedented. Cr is confirmed to be a prerequisite to ensure self-protection against corrosion by passivation. Adding Mo up to 10 at.% tremendously enhances the resistance to passivity breakdown in Cl--containing aggressive environment. Newly designed quinary alloys, Cr25Fe25Co5Ni40Mo5 and Cr15Fe10Co5Ni60Mo10 (at.%), show superior resistance to localized corrosion.

As 5-HTPatient subgroups, with and without triptan contraindications, were analyzed from pooled patient data from four randomized, double-blind, placebo-controlled clinical trials (SAMURAI, SPARTAN, CENTURION, and MONONOFU). Patients experiencing a single migraine attack of moderate or severe intensity were treated with lasmiditan 50 mg (SPARTAN and MONONOFU only), 100 mg, 200 mg, or placebo, and efficacy data were recorded in an electronic diary.Of 5704 patients, 207 (3.6%) patients had at least one contraindication to triptans. Overall subgroup analysis revealed that the effects of lasmiditan on pain freedom, pain relief, freedom from most bothersome symptom, disability freedom, and Patient Global Impression of Change at 2 h post-dose did not differ in patient groups with and without triptan contraindications. These outcomes generally showed a similar benefit pattern for lasmiditan in both subgroups, with all results being statistically significant in patients without contraindications, and pain relief being statistically significant in patients with contraindications. The safety and tolerability profiles of patients with triptan versus without triptan contraindications were similar, including dizziness in 18.3 to 22.8% and somnolence in 7.9 to 9.9% of patients at the highest dose of lasmiditan.In pooled analyses from four trials, patients with and without triptan contraindications did not differ in their patterns of lasmiditan efficacy. Lasmiditan may be a treatment option in patients with contraindications to triptans.SAMURAI, NCT:02439320; SPARTAN, NCT:02605174; CENTURION, NCT:03670810; and MONONOFU, NCT:03962738.

A key factor for effective inhibition by organic molecules of the initiation of localized corrosion by pitting is their ability to form a protective organic film in locally de-passivated zones exposing the bare metal next to the oxide-covered surface. Herein, based on quantum chemical DFT calculations, we study the chemistry of the interface between 2-mercaptobenzimidazole (MBI) and a copper surface partially covered by a Cu2O passive oxide film. The results show the adaptability of the molecule to adsorb strongly on the different zones, oxide or metal, of a locally de-passivated surface. However, differences in the local adsorption configurations, involving covalent bonding with H-bonding depending on oxide or metal and on conformer, thione or thiolate, lead to the formation of an inhomogeneous organic film. Increasing order of local adsorption strength is oxide walls < metal surface < oxide surface < oxide edges for the thione species, whereas there is no significant difference of local adsorption strength for the thiolate species. Our results suggest that both species of MBI can heal the oxygen and copper low coordinated sites as well as can protect the exposed metal surface, thus enhancing the barrier properties of the passivated surface even when locally defective.

DFT calculations bringing atomic scale insight into the corrosion inhibition properties of 2-mercaptobenzothiazole on copper are reported. Energetic and electronic analysis show that both the thione and thiolate conformers strongly chemisorb on oxide-free Cu(110) surfaces and can self-order to form dense and stable organic barriers saturating all Cu atoms of the topmost metal plane. Increasing monolayer density occurs at the cost of the metal and molecule deformations, but the energy loss is compensated by the layer cohesion energy. The copper vacancy creation energy is higher with thiolate than with thione monolayers, indicating more efficient mitigation of dissolution by adsorbed thiolate.

The effects of water on 2-mercaptobenzothiazole (2-MBT) film pre-formed on copper at low pressure and room temperature was investigated in situ by X-ray photoelectron spectroscopy. Upon exposure to water vapour at 5 × 10-6 mbar, the 2-MBT molecules not directly bonded to copper desorb, until only one monolayer remains adsorbed. Further exposure leads to cleavage of the bond between exocyclic sulphur and copper, whereas nitrogen remains bonded to copper. Dissociative adsorption of water is observed, without copper oxidation for exposure up to 3 × 106 L. This work brings new molecular scale insight into corrosion inhibition mechanisms in water-containing environments.

A combined X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry and electrochemical approach was used to investigate the mechanisms of molybdenum and chromium enrichment of a passive lm formed on a model austenitic stainless steel single crystal in aqueous acid media and the effect that thermal pre-oxidation at 250 C plays in the composition, thickness, and stratification of the film. A clean FeCrNiMo (100)-oriented surface, prepared under ultra-high vacuum (UHV), was exposed to ultra-low pressures of oxygen at 250°C, forming a thin oxide film, rich in iron and chromium, as well as containing molybdenum. An argon- lled glovebox, directly attached to the UHV system, allowed for electrochemical alterations to be carried out without exposure to ambient air. After being held at open circuit potential for 30 minutes, hydroxylation of chromium and molybdenum was promoted, with a marked enrichment of both elements in the oxide film. A distinct bilayer film was observed. Anodic polarisation resulted in a significant growth of the inner layer and further enrichment of chromium. Pre-oxidation at 250°C, using an ultra-low pressure of oxygen, was found to promote protection against transient active dissolution during anodic passivation, and to cause enrichment of molybdenum in the outer layer of the passive film.

Migraine, the most frequent neurological ailment, affects visual processing during and between attacks. Most visual disturbances associated with migraine can be explained by increased neural hyperexcitability, as suggested by clinical, physiological and neuroimaging evidence. Here, we review how simple (e.g., patterns, color) visual functions can be affected in patients with migraine, describe the different complex manifestations of the so-called Alice in Wonderland Syndrome, and discuss how visual stimuli can trigger migraine attacks. We also reinforce the importance of a thorough, proactive examination of visual function in people with migraine.

A model experimental approach, providing molecular scale insight into the build up mechanisms of a corrosion inhibiting interface, is reported. 2-mercaptobenzimidazole (2-MBI), a widely used organic inhibitor, was deposited from the vapor phase at ultra-low pressure on copper surfaces in chemically-controlled state, and X-ray photoelectron spectroscopy was used in situ to characterize the adsorption mechanisms upon formation of the inhibiting film. On copper surfaces prepared clean in the metallic state, the intact molecules lie flat at low exposure, with sulfur and both nitrogen atoms bonded to copper. A fraction of the molecules decomposes upon adsorption, leaving atomic sulfur on copper. At higher exposure, the molecules adsorb in a tilted position with sulfur and only one nitrogen bonded to copper, leading to a densification of 2-MBI in the monolayer. A bilayer is formed at saturation with the outer layer not bonded directly to copper. In the presence of a pre-adsorbed 2D oxide, oxygen is substituted and the molecules adsorb intactly without decomposition. A 3D oxide prevents the bonding of sulfur to copper. The molecular film formed on metallic and 2D oxide pre-covered surfaces partially desorbs and decomposes at temperature above 400 °C, leading to the adsorption of atomic sulfur on copper.

In this manuscript we pay a tribute to Pierre Marie (1853-1940), highlighting his great contribution to medicine and neurology describing several diseases and syndromes. We mainly emphasize aspects of his personal life and personality traits. Considered one of the three greatest neurologists of the late nineteenth and early twentieth centuries, his brilliant career began at La Salpêtrière, followed by the development of a neurological school at Hospice Bicêtre. Pierre Marie had numerous disciples around the world, including Brazil, and published on various neurological and endocrinological themes. Back to La Salpêtrière, he concluded his professional life as a Neurology leader. However, after retirement, his demise was sad and lonely RESUMO Neste manuscrito, prestamos homenagem a Pierre Marie (1853-1940), destacando sua grande contribuição para a medicina e a neurologia, descrevendo várias doenças e síndromes. Enfatizamos principalmente aspectos de sua vida pessoal e traços de personalidade. Considerado um dos três maiores neurologistas do final do século XIX e início do século XX, sua brilhante carreira começou em La Salpêtrière, seguida pelo desenvolvimento de uma escola de neurologia no Hospice Bicêtre. Pierre Marie teve numerosos discípulos em todo o mundo, incluindo o Brasil, e publicou sobre vários temas neurológicos e endocrinológicos. De volta a La Salpêtrière, ele concluiu sua vida profissional como líder da Neurologia. Porém, após aposentadoria, seu ocaso foi triste e solitário

Very few topics in the headache field engender more controversy than sinus headache. Patients often believe that their headaches are attributed to sinus disorders because they experience rhinitis symptoms (e.g. rhinorrhoea, nasal congestion, and postnasal drip) during their attacks. Primary care physicians, otolaryngologists, and allergists often diagnose sinus headaches and treat them with rhinitis medications, antibiotics, allergy shots, and surgical interventions, with varying levels of success. In contrast, most neurologists and headache specialists believe that many patients with a diagnosis of sinus headache are suffering from migraine, or another primary headache disorder.

Optical frequency standards, lasers stabilized to atomic or molecular transitions, are widely used in length metrology and laser ranging, provide a backbone for optical communications and lie at the heart of next-generation optical atomic clocks. Here we demonstrate a compact, low-power optical frequency standard based on the Doppler-free, two-photon transition in rubidium-87 at 778 nm implemented on a micro-optics breadboard. The optical standard achieves a fractional frequency stability of 2.9x10$^{-12}$/$\sqrt{\tau}$ for averaging times $\tau$ less than 10$^{3}$ s, has a volume of $\approx$35 cm$^3$ and operates on $\approx$450 mW of electrical power. These results demonstrate a key step towards the development of compact optical clocks and the broad dissemination of SI-traceable wavelength references., Comment: 4 pages, 4 figures

While migraine headaches can be provoked, or predicted by the presence of an aura or premonitory symptoms, the prediction or elicitation of the aura itself is more problematic. Therefore, imaging studies directly examining the aura phenomenon are sparse. There are however interictal imaging studies that can shed light on the pathophysiology of the migraine with aura (MWA) cascade. Here, we review findings pointing to the involvement of cortical spreading depression (CSD) and neuroinflammation in MWA. Whether asymptomatic CSD also happens in some migraine without aura is still under debate. In addition, new evidence points to glial activation in MWA, indicating the involvement of astrocytes in the neuroinflammatory cascade that follows CSD, as well as dural macrophages, supporting the involvement of the trigeminovascular system in migraine pain.

Supplementary Text

Supplementary Text

A substantial body of research has shown that Parkinson disease (PD) patients display an enlarged hyperechogenic substantia nigra (SN) by transcranial sonography (TCS). Nonetheless, the categorization of SN echogenicity is still subjective. A method is described to quantify SN echogenicity based on the gray-level histograms of digitized TCS images. In 31 PD patients and 57 controls, the gray-scale mean (GSM) of the SN, mesencephalon, and basal cisterns and their ratios were assessed using image-editing computer software. The GSM values were compared between the groups and correlated with age, SN area, and disease duration. The SN GSM was significantly higher in the PD group ( P < .05) with a positive correlation with age but not with disease duration. In this cohort of participants, mesencephalon echogenicity was found to increase with disease duration. These results would suggest quantitatively SN hyperechogenicity in PD. Quantifying SN echogenicity is feasible and might minimize subjectivity in PD diagnosis by TCS. The method has the potential to disclose subtle changes in other midbrain structures’ echogenicity engendered by the disease process as well.

Given that the medial olivocochlear efferent system reduces the amplitude of otoacoustic emissions (OAE), the aim of this study was to establish whether such a pathway is affected in women with migraine and phonophobia by means of OAE suppression testing. In this prospective case-control study, 55 women (29 with migraine and phonophobia and 26 healthy women) were subjected to transient-evoked otoacoustic emission (TEOAE) testing at frequencies from 1 to 4 kHz. The amplitudes of the TEOAE response before and after exposure to contralateral noise and the magnitude of TEOAE suppression were assessed. The average TEOAE amplitudes in conditions with and without exposure to contralateral noise were not significantly different between the groups. However, the magnitude of TEOAE suppression was lower in the group with migraine; that difference was only statistically significant for frequencies 1 and 1.5 kHz (p = 0.042 and p = 0.004, respectively). In this study, women with migraine and phonophobia exhibited deficits in OAE suppression, which points to a disorder affecting the medial olivocochlear efferent system.

Made available in DSpace on 2021-07-14T10:18:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-03. Added 1 bitstream(s) on 2021-07-14T11:26:49Z : No. of bitstreams: 1 S0004-282X2016000300017.pdf: 296980 bytes, checksum: 61532e35d8a3544c1e4f26fc993603b3 (MD5) Neste artigo um grupo de especialistas no tratamento de cefaleia da Sociedade Brasileira de Cefaleia através de um consenso elaborou medidas estratérgicas para tratar uma crise de migrânea tanto na criança como no adulto. Uma enfase particular foi dada no tratamento da migranea na mulher, incluindo gravidez, lactação e período perimenstrual. In this article, a group of experts in headache management of the Brazilian Headache Society developed through a consensus strategic measurements to treat a migraine attack in both the child and the adult. Particular emphasis was laid on the treatment of migraine in women, including at pregnancy, lactation and perimenstrual period. Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto Universidade Federal de São Paulo, Escola Paulista de Medicina Universidade Federal do Rio Grande do Norte Universidade do Federal do Paraná Faculdade de Medicina de Catanduva Universidade Federal Ciências da Saúde de Porto Alegre Hospital Mário Gartti Universidade Federal Fluminense Universidade Estadual de Campinas Unichristus Hospital Geral de Fortaleza Universidade Federal de Santa Catarina Sociedade Brasileira de Cefaleia Universidade Federal de Pernambuco Hospital Esperança Universidade Estadual Júlio de Mesquita Filho Universidade Federal do Rio de Janeiro Faculdade de Medicina de Barbacena Santa Casa de São Paulo Universidade Federal de Minas Gerais Universidade Estadual Júlio de Mesquita Filho

Vertigo symptoms and subclinical vestibular dysfunctions may occur in migraine. The Minimal Caloric Test (MCT), an easy-to-perform, convenient and yet informative procedure was used to test the vestibular function in 30 vertigo-free migraine patients outside attacks and 30 paired controls. Although not statistically significant, a right-to-left nystagmus duration asymmetry greater than 25% was present in both groups. This difference was greater in the patients group, suggesting the presence of subclinical vestibular imbalance in migraine. RESUMO Vertigem e alterações vestibulares subclínicas têm sido identificadas na enxaqueca. O teste calórico mínimo é simples de realizar, informativo e conveniente. Ele foi realizado em 30 pacientes com enxaqueca sem queixa de vertigem e 30 controles pareados. Embora não estatisticamente significativo, ocorreu assimetria direita-esquerda superior a 25% na duração do nistagmo em ambos os grupos, maior nos pacientes, o que sugere a presença de desequilíbrio vestibular subclínico na enxaqueca.

Duchenne de Boulogne is known mainly by the disease eponymously named “Duchenne muscular dystrophy”, or pseudohypertrophic muscular dystrophy, although some experts consider that the original description of this disease does not belong to him. Less well known are the facts related to the tragic death of his beloved wife shortly after the birth of his only child, the unjustifiable distance he was forced to keep from this son for more than 30 years, and of being humiliated and professionally despised by his peers. These events made the life of this physician, physiologist, researcher and inventor extremely arduous. We emphasize some aspects of the history of this man, his work and his life, a true genius of few friends. RESUMO Duchenne de Boulogne é conhecido por muitos principalmente devido à doença que leva seu nome - doença de Duchenne ou Distrofia Muscular Pseudo-hipertrófica - embora alguns historiadores considerem que a descrição original desta doença não lhe pertence. Menos conhecidos são os fatos relacionados à morte trágica de sua amada esposa logo após o nascimento de seu filho, o afastamento injusto que foi forçado a manter deste filho único por mais de 30 anos, e ser humilhado e profissionalmente desprezado por seus pares da comunidade neurológica, que em conjunto tornaram a vida desse médico, fisiologista, pesquisador e inventor, extremamente árdua. Enfatizamos alguns aspectos da história deste homem, seu trabalho e ocaso, protótipo de um verdadeiro gênio de poucos amigos.

Objective The main goal of this study was to correlate migraine improvement, after prophylactic therapy, with cortical thickness changes. Methods Cortical thickness maps were obtained with magnetic resonance imaging (MRI) from 19 patients with migraine before (first scan) and after (second scan) prophylactic treatment, and these were compared with controls using the FreeSurfer MRI tool. Cortical changes were correlated with the headache index (HI). Results Anincrease incortical thickness was found in the right cuneus and precuneus, somatosensory and superior parietal cortices in both patient scans, compared with the controls. No changes were observed in the left hemisphere. Following correction for multiple comparisons, no areas changed from the first to the second scan. Regression analysis showed a significant negative correlation between the HI improvement and cortical thickness changes in the left posterior cingulate, a region involved with nociception and, possibly, the development of chronic pain. Conclusion There were changes in cortical thickness in patients with migraine relative to controls in areas involved with vision and pain processing. Left posterior cingulate cortical changes correlated with headache frequency and intensity. RESUMO Objetivos Correlacionar a melhora de pacientes enxaquecosos após tratamento preventivo com alterações na espessura do córtex cerebral. Métodos Espessura cortical foi determinada a partir de imagens de ressonância magnética (RM)em 19 pacientes com enxaqueca, antes (1ᵃ RM) e após (2ᵃ RM) o tratamento profilático, e comparada com controles, usando o programa FreeSurfer. Mudanças corticais foram correlacionadas com o índice de cefaleia (HI). Resultados O hemisfério direito apresentou aumento da espessura no córtex do cúneus e pré-cúneus, parietal superior e somatossensitivo na primeira RM e na segunda RM, em comparação aos controles. Após correção para comparações múltiplas, nenhuma região cortical se mostrou estatisticamente diferente entre a primeira e a segunda RM. A regressão mostrou correlação (negativa) significativa entre melhora do HI e mudanças na espessura cortical do cíngulo posterior esquerdo. Conclusão Existem alterações de espessura cortical em pacientes com enxaqueca em relação a controles em áreas envolvidas com processamento visual e com a dor. As alterações corticais no cíngulo posterior esquerdo variaram de acordo com a frequência e intensidade das crises.

Migraine and vertigo are common disorders, with lifetime prevalences of 16% and 7% respectively, and co-morbidity around 3.2%. Vestibular syndromes and dizziness occur more frequently in migraine patients. We investigated bedside clinical signs indicative of vestibular dysfunction in migraineurs. Objective To test the hypothesis that vestibulo-ocular reflex, vestibulo-spinal reflex and fall risk (FR) responses as measured by 14 bedside tests are abnormal in migraineurs without vertigo, as compared with controls. Method Cross-sectional study including sixty individuals – thirty migraineurs, 25 women, 19-60 y-o; and 30 gender/age healthy paired controls. Results Migraineurs showed a tendency to perform worse in almost all tests, albeit only the Romberg tandem test was statistically different from controls. A combination of four abnormal tests better discriminated the two groups (93.3% specificity). Conclusion Migraine patients consistently showed abnormal vestibular bedside tests when compared with controls. Enxaqueca e vertigem são desordens comuns, com prevalência de 16% e 7% respectivamente, e comorbidade em torno de 3,2%. Síndromes vestibulares e tonturas ocorrem mais frequentemente em enxaquecosos. Pesquisamos alterações vestibulares utilizando testes de beira-de-leito em enxaquecosos. Objetivo Verificar se as respostas dos reflexos vestíbulo-ocular, vestíbulo-medular e risco de quedas medidas por 14 testes de beira-de-leito são diferentes comparando-se enxaquecosos sem vertigem, e controles. Método Estudo transversal com sessenta pessoas, 30 enxaquecosos; 25 mulheres, 19-60 anos; e trinta controles saudáveis pareados por sexo e idade. Resultados Houve tendência de pior desempenho entre enxaquecosos em quase todos testes, porém apenas o teste de Romberg tandem foi estatisticamente diferente dos controles. Uma combinação de quatro testes anormais discrimina os grupos com especificidade de 93,3%. Conclusão O grupo de enxaquecosos mostrou consistentemente testes vestibulares de beira-de-leito anormais quando comparados a controles.

Background Migraine, particularly chronic migraine (CM), is underdiagnosed and undertreated worldwide. Our objective was to develop and validate a self-administered tool (ID-CM) to identify migraine and CM. Methods ID-CM was developed in four stages. (1) Expert clinicians suggested candidate items from existing instruments and experience (Delphi Panel method). (2) Candidate items were reviewed by people with CM during cognitive debriefing interviews. (3) Items were administered to a Web panel of people with severe headache to assess psychometric properties and refine ID-CM. (4) Classification accuracy was assessed using an ICHD-3β gold-standard clinician diagnosis. Results Stages 1 and 2 identified 20 items selected for psychometric validation in stage 3 ( n = 1562). The 12 psychometrically robust items from stage 3 underwent validity testing in stage 4. A scoring algorithm applied to four symptom items (moderate/severe pain intensity, photophobia, phonophobia, nausea) accurately classified most migraine cases among 111 people (sensitivity = 83.5%, specificity = 88.5%). Augmenting this algorithm with eight items assessing headache frequency, disability, medication use, and planning disruption correctly classified most CM cases (sensitivity = 80.6%, specificity = 88.6%). Discussion ID-CM is a simple yet accurate tool that correctly classifies most individuals with migraine and CM. Further testing in other settings will also be valuable.

Background Migraine, a common brain disorder, disrupts vision more than any other motor or sensory function. The possible visual aura symptoms vary from occasional small flashes of light to complex visual hallucinations, the stereotyped teichopsia being the most typical pattern. It is unclear as to why aura occurs serendipitously, sometimes preceding, but also occurring after the headache, and why aura can present with multiple phenotypes. Methods To better understand the nature of visual disturbances in migraine, 4 aspects must be considered: What are the visual perceptions in migraine; why vision is affected in migraine; the role of cortical spreading depression (CSD); how does vision could affect migraine. Evidence supporting each of these topics is reviewed. Results CSD travels at a similar pace as the march of symptoms in the visual field. Functional neuroimaging studies show spreading changes compatible with CSD regardless of aura. Computerized models reproducing the CSD march on the visual cortex predict a sensory experience compatible with naturally occurring visual auras. Rather than spreading in all directions, these models suggest that CSD moves preferentially in one direction. Migraine-preventive drugs increase the CSD threshold and reduce CSD velocity. Blind migraineurs may present atypical visual aura, with more colors, shorter duration, different shapes, and atypical symptoms, such as auditory experiences. Conclusions CSD is the underlying phenomenon in migraine with and without aura. In migraine without aura, CSD probably does not run over silent areas of the cortex, but rather does not reach symptomatology threshold. Normal vision is important in migraine, as lack of sight may change the visual experience during migraine aura, probably due to cortical reorganization and changes in local susceptibility to CSD.

Migraine is a central nervous system disorder frequently expressed with paroxysmal visual dysfunctions. Objective To test the hypothesis that normal visual input is vital for the migrainous aura and photophobia. Method We studied the migraine-related visual disturbances in 8 sightless migraineurs identified among 200 visually impaired subjects. Results The main findings were the visual aura and photophobia disappearance along with blindness development, the oddness of aura – too short, colourful (e.g. blue or fire-like), auditory in nature or different in shape (round forms) – and the lack of photophobia. Conclusion We propose that the aura duration should be accepted as shorter in visually impaired subjects. The changes in aura phenotype observed in our patients may be the result of both cerebral plasticity induced by the visual impairment and/or the lack of visual input per se. Integrity of visual pathways plays a key role in migraine visual aura and photophobia.

Charles Lasègue is reputed to have described the test/sign bearing his name, but he never wrote about it and misinterpreted its mechanism. The purpose of this note is to highlight the work of the Serbian, Laza Lazarević, who was first to present the original report of this seminal sign in sciatica and provide its appropriate pathophysiological interpretation.

Physical therapy may be of great importance in Parkinson disease. The objective of the study is to analyze the gait in patients with Parkinson disease treated with an equipment of body weight support associated with a treadmill as compared with the conventional physical therapy. All subjects presented lower fatigue at the last session than at baseline. The body weight support associated with a treadmill group showed signifi cant improvement in Unifi ed Parkinson’s Disease Rating Scale motor scale score, while the conventional physical therapy group improved in the 6-minute walk test distance parameter. No technique proved universally better than another, and treatments led to good results considering

Hemicrania continua (HC) is a well-known primary headache. The present version of the International Classification of Headache Disorders lists HC in the "other primary headaches" group. However, evidence has emerged demonstrating that HC is a phenotype that belongs to the trigeminal autonomic cephalalgias together with cluster headache, paroxysmal hemicrania (PH), and short-lasting, unilateral neuralgiform headache attacks with conjunctival injection and tearing. This is supported by a common general clinical picture - paroxysmal, fluctuating, unilateral, side-locked headaches located to the ocular, frontal, and/or temporal regions, accompanied by ipsilateral autonomic dysfunctions including for example, tearing and conjunctival injection. Apart from the remarkable clinical similarities, the absolute and incomparable effect of indomethacin in HC parallels the effect of this drug in PH, suggesting a shared core pathogenesis. Finally, neuroimage findings demonstrate a posterior hypothalamic activation in HC similarly to cluster headache, PH, and short-lasting, unilateral neuralgiform headache attacks with conjunctival injection and tearing. Taken together, data indicate that HC is certainly a type of trigeminal autonomic cephalalgia that should no longer be placed in a group of miscellaneous primary headache disorders.

Background. Parsonage-Turner syndrome, or neuralgic amyotrophy (NA), is an acute brachial plexus neuritis that typically presents with unilateral shoulder pain and amyotrophy but also can affect other peripheral nerves, including the recurrent laryngeal nerve. Idiopathic vocal fold paralysis (VFP) represents approximately 12% of the VFP cases and recurrence is extremely rare.Methods and Results. We report a man with isolated recurrent unilateral right VFP and a diagnosis of NA years before.Conclusions. We emphasize that shoulder pain and amyotrophy should be inquired in any patient suffering from inexplicable dysphonia, and Parsonage-Turner syndrome should be considered in the differential diagnosis of idiopathic VFP.

Consenso Latinoamericano para las Directrices de Tratamiento de la Migraña Crónica. Headache Medicine. 2012;3(4)

Chronic migraine is a condition with significant prevalence all around the world and high socioeconomic impact, and its handling has been challenging neurologists. Developments for understanding its mechanisms and associated conditions, as well as that of new therapies, have been quick and important, a fact which has motivated the Latin American and Brazilian Headache Societies to prepare the present consensus. The treatment of chronic migraine should always be preceded by a careful diagnosis review; the detection of possible worsening factors and associated conditions; the stratification of seriousness/impossibility to treat; and monitoring establishment, with a pain diary. The present consensus deals with pharmacological and nonpharmacological forms of treatment to be used in chronic migraine. A migrânea crônica é uma condição com prevalência significativa ao redor do mundo e alto impacto socioeconômico, sendo que seu manuseio tem desafiado os neurologistas. Os avanços na compreensão de seus mecanismos e das condições a ela associadas, bem como nas novas terapêuticas, têm sido rápidos e importantes, fato que motivou as Sociedades Latino-americana e Brasileira de Cefaleia a elaborarem o presente consenso. O tratamento da migrânea crônica deve ser sempre precedido por uma revisão cuidadosa do diagnóstico, pela detecção de possíveis fatores de piora e das condições associadas, pela estratificação de gravidade/impossibilidade de se tratar e pelo monitoramento com um diário da dor. Este consenso apresenta abordagens farmacológicas e não-farmacológicas para tratar a migrânea crônica.

Chip-scale atomic clocks (CSACs) provide unprecedented frequency stability within volumes down to a fewcubic centimeters and power consumptions as low as 100mW.In this work, we determine the optimal parameters regarding the design and the fabrication of cesium vaporcells, one of the key components of a CSAC. For this purpose, cells were characterized on both short and longtermperformances in clock setups. In addition, we propose solutions to overcome present limitations includingthe operating temperature range, the device microfabrication cost and the ease of integration of the physicspackage.A novel mixture of buffer-gas composed of neon and helium was found to potentially extend the operating rangeof the device above 80 C, meeting the industrial requirements. Unlike the well-known buffer gas compositions,this mixture is compatible with solid cesium dispensers whose reliability is established. As an alternativeto buffer gases, wall coatings are known to limit the relaxation induced by sidewalls. Here, we investigatedoctadecyltrichlorosilane (OTS) coatings. An anti-relaxation effect has been observed in centimeter-scale cellsand a process was developed to coat microfabricated cells.Other cesium sources have been investigated to overcome the drawbacks imposed by solid cesium dispensers. Apaste-like dispenser, which can be deposited collectively, was explored and has shown stable atomic densities sofar. Single-use zero-leak micro valves were also proposed to hermetically seal and detach cells from a commoncesium reservoir.Eventually, the first steps toward a microfabricated physics package were made. In particular, an originalcell design combining diffraction gratings with an anisotropically etched single-crystalline silicon sidewalls wascharacterized and exhibited remarkable CPT contrasts despite a reduced cavity volume, which could lead to amore compact physics package. Finally, cells with integrated heating and temperature sensing resistors werefabricated and their magnetic field compliance was characterized in a compact physics package prototype.; Les horloges atomiques miniatures présentent des stabilités de fréquence inégalées avec des volumes de quelquescentimètres cubes et des consommations inférieures à 100mW.Dans cette thèse, les paramètres optimaux concernant la conception et la fabrication des cellules à vapeur decésium, un des composant clés de ce type d’horloges, sont définis. Ainsi, les performances de plusieurs cellulesont été caractérisées en condition d’horloge à court et long terme. En parallèle, des solutions sont proposéespour pallier à certaines limitations telles que la plage de température opérationnelle, le coût de fabrication dudispositif et la facilité d’assemblage du module physique.Un nouveau mélange de gaz tampon composé de néon et d’hélium peut étendre la plage de fonctionnementau-dessus de 80 C, en adéquation avec les besoins industriels. A l’inverse des gaz tampon usuels, ce mélangeest compatible avec les dispensers de césium solides, dont la fiabilité est établie.Outre les gaz tampon, les revêtements permettent également de limiter la relaxation induite par les parois dela cellule. Ici, des revêtements d’octadécyltrichlorosilane sont étudiés. Un effet anti-relaxant a été observé dansdes cellules centimétriques et un procédé a été développé pour revêtir des cellules micro-fabriquées.D’autres sources de césium sont présentées pour s’affranchir des inconvénients propres aux dispensers solides.Un dispenser sous forme de pâte, qui peut être déposée collectivement, a été étudié et montre des densitésatomiques stables jusqu’à présent. Un concept de vannes hermétiques micro-fabriquées a été proposé poursceller hermétiquement et séparer des cellules d’un réservoir de césium commun.Les premières étapes vers un module physique micro-fabriqué sont ensuite présentées. En particulier, un designoriginal de cellule combinant des réseaux de diffraction à une cavité en silicium formée par gravure anisotropea été caractérisé et a montré des contrastes CPT remarquables malgré un volume de cavité réduit, ce qui permettraitde réaliser un module physique particulièrement compact. Enfin, des cellules intégrant des résistanceschauffantes et thermométriques ont été fabriquées et leur compatibilité vis-à-vis du champ magnétique généréa été caractérisée dans un prototype de module physique compact.

Background Jumping to conclusions due to impulsivity has been shown to be a sensitive marker for dopamine dysregulation and addictive behaviour patterns in treated patients with Parkinson's disease (PD). It is unknown whether drug naive PD patients, who have never received dopaminergic therapy also have deficits in information sampling. Methods Twenty five de novo PD patients and twenty matched healthy controls were recruited and tested on the beads task, which is a validated information sampling task to assess reflection impulsivity and a temporal discounting questionnaire. Results Patients gathered significantly less information and made more irrational choices than matched controls. There was, however, no group difference on the temporal discounting questionnaire. Conclusions Poor information sampling and irrational decision making may be an inherent component of the neuropsychological deficit in Parkinson's disease. These findings suggest that underlying impulsivity detected by a metric task is common in de novo PD.