823 research outputs found
Experiência homossexual no contexto escolar
Neste artigo, partimos da utilização da carta de uma estudante adolescente à sua professora de Ciências, atribuindo a essa relação e à Escola sentidos atravessados por saber/poder. Uma carta que nos convida a olhar como vamos nos constituindo como sujeitos de desejo e como vamos acionando saberes para sermos capazes de produzir saberes sobre nós mesmos, tomando-nos como objeto de investigação. Dessa maneira, a questão que se coloca como foco deste artigo é, então, o que faz dos sujeitos, sujeitos de uma sexualidade específica, o que faz dos sujeitos, homossexuais. Trata-se de uma questão atual, que parte da atualidade para questionar a ideia de experiência homossexual como o encontro tenso entre os jogos de verdade, poder e subjetividades. Eis a tensão que nos faz reconhecer-nos como sujeitos sexuais
Migraine and vascular disease biomarkers: A population-based case-control study.
Background The underpinnings of the migraine-stroke association remain uncertain, but endothelial activation is a potential mechanism. We evaluated the association of migraine and vascular disease biomarkers in a community-based population. Methods Participants (300 women, 117 men) were recruited as a part of the Dutch CAMERA 1 (Cerebral Abnormalities in Migraine, an Epidemiologic Risk Analysis) study. Participants were aged 30-60 (mean 48) years, 155 migraine had with aura (MA), 128 migraine without aura (MO), and 134 were controls with no severe headaches. Plasma concentrations of fibrinogen, Factor II, D-dimer, high sensitivity C-reactive protein (hs-CRP), and von Willebrand factor antigen were compared between groups, also stratifying by sex. Results Fibrinogen and hs-CRP were elevated in migraineurs compared to controls. In logistic regression analyses, MO and MA had increased likelihood of elevated fibrinogen, and MA had increased likelihood of elevated Factor II and hs-CRP. Fibrinogen and Factor II were associated with MA in women but not men. In the migraine subgroup, the total number of years of aura, but not headache, predicted elevated hs-CRP, and the average number of aura, but not headache, attacks predicted all biomarkers but Factor II. Conclusions Elevated vascular biomarkers were associated with migraine, particularly MA, as well as with years of aura and number of aura attacks
Familial hemiplegic migraine CaV2.1 channel mutation R192Q enhances ATP-gated P2X3 receptor activity of mouse sensory ganglion neurons mediating trigeminal pain
<p>Abstract</p> <p>Background</p> <p>The R192Q mutation of the CACNA1A gene, encoding for the α1 subunit of voltage-gated P/Q Ca<sup>2+ </sup>channels (Ca<sub>v</sub>2.1), is associated with familial hemiplegic migraine-1. We investigated whether this gain-of-function mutation changed the structure and function of trigeminal neuron P2X<sub>3 </sub>receptors that are thought to be important contributors to migraine pain.</p> <p>Results</p> <p>Using in vitro trigeminal sensory neurons of a mouse genetic model knockin for the CACNA1A R192Q mutation, we performed patch clamp recording and intracellular Ca<sup>2+ </sup>imaging that showed how these knockin ganglion neurons generated P2X<sub>3 </sub>receptor-mediated responses significantly larger than wt neurons. These enhanced effects were reversed by the Ca<sub>v</sub>2.1 blocker ω-agatoxin. We, thus, explored intracellular signalling dependent on kinases and phosphatases to understand the molecular regulation of P2X<sub>3 </sub>receptors of knockin neurons. In such cells we observed strong activation of CaMKII reversed by ω-agatoxin treatment. The CaMKII inhibitor KN-93 blocked CaMKII phosphorylation and the hyperesponsive P2X<sub>3 </sub>phenotype. Although no significant difference in membrane expression of knockin receptors was found, serine phosphorylation of knockin P2X<sub>3 </sub>receptors was constitutively decreased and restored by KN-93. No change in threonine or tyrosine phosphorylation was detected. Finally, pharmacological inhibitors of the phosphatase calcineurin normalized the enhanced P2X<sub>3 </sub>receptor responses of knockin neurons and increased their serine phosphorylation.</p> <p>Conclusions</p> <p>The present results suggest that the CACNA1A mutation conferred a novel molecular phenotype to P2X<sub>3 </sub>receptors of trigeminal ganglion neurons via CaMKII-dependent activation of calcineurin that selectively impaired the serine phosphorylation state of such receptors, thus potentiating their effects in transducing trigeminal nociception.</p
Libration-induced Orbit Period Variations Following the DART Impact
The Double Asteroid Redirection Test (DART) mission will be the first test of a kinetic impactor as a means of planetary defense. In late 2022, DART will collide with Dimorphos, the secondary in the Didymos binary asteroid system. The impact will cause a momentum transfer from the spacecraft to the binary asteroid, changing the orbit period of Dimorphos and forcing it to librate in its orbit. Owing to the coupled dynamics in binary asteroid systems, the orbit and libration state of Dimorphos are intertwined. Thus, as the secondary librates, it also experiences fluctuations in its orbit period. These variations in the orbit period are dependent on the magnitude of the impact perturbation, as well as the system’s state at impact and the moments of inertia of the secondary. In general, any binary asteroid system whose secondary is librating will have a nonconstant orbit period on account of the secondary’s fluctuating spin rate. The orbit period variations are typically driven by two modes: a long period and a short period, each with significant amplitudes on the order of tens of seconds to several minutes. The fluctuating orbit period offers both a challenge and an opportunity in the context of the DART mission. Orbit period oscillations will make determining the post-impact orbit period more difficult but can also provide information about the system’s libration state and the DART impact
Guidelines of the International Headache Society for controlled trials of preventive treatment of chronic migraine in adults
Background Quality clinical trials form an essential part of the evidence base for the treatment of headache disorders. In 1991, the International Headache Society Clinical Trials Standing Committee developed and published the first edition of the Guidelines for Controlled Trials of Drugs in Migraine. In 2008, the Committee published the first specific guidelines on chronic migraine. Subsequent advances in drug, device, and biologicals development, as well as novel trial designs, have created a need for a revision of the chronic migraine guidelines. Objective The present update is intended to optimize the design of controlled trials of preventive treatment of chronic migraine in adults, and its recommendations do not apply to trials in children or adolescents
A prospective open label 2-8 year extension of the randomised controlled ICON trial on the long-term efficacy and safety of occipital nerve stimulation in medically intractable chronic cluster headache
BACKGROUND: We demonstrated in the randomised controlled ICON study that 48-week treatment of medically intractable chronic cluster headache (MICCH) with occipital nerve stimulation (ONS) is safe and effective. In L-ICON we prospectively evaluate its long-term effectiveness and safety. METHODS: ICON participants were enrolled in L-ICON immediately after completing ICON. Therefore, earlier ICON participants could be followed longer than later ones. L-ICON inclusion was stopped after the last ICON participant was enrolled in L-ICON and followed for ≥2 years by completing six-monthly questionnaires on attack frequency, side effects, subjective improvement and whether they would recommend ONS to others. Primary outcome was the change in mean weekly attack frequency 2 years after completion of the ICON study compared to baseline. Missing values for log-transformed attack-frequency were imputed for up to 5 years of follow-up. Descriptive analyses are presented as (pooled) geometric or arithmetic means and 95% confidence intervals. FINDINGS: Of 103 eligible participants, 88 (85%) gave informed consent and 73 (83%) were followed for ≥2 year, 61 (69%) ≥ 3 year, 33 (38%) ≥ 5 years and 3 (3%) ≥ 8.5 years. Mean (±SD) follow-up was 4.2 ± 2.2 years for a total of 370 person years (84% of potentially 442 years). The pooled geometric mean (95% CI) weekly attack frequency remained considerably lower after one (4.2; 2.8-6.3), two (5.1; 3.5-7.6) and five years (4.1; 3.0-5.5) compared to baseline (16.2; 14.4-18.3). Of the 49/88 (56%) ICON ≥50% responders, 35/49 (71%) retained this response and 15/39 (38%) ICON non-responders still became a ≥50% responder for at least half the follow-up period. Most participants (69/88; 78% [0.68-0.86]) reported a subjective improvement from baseline at last follow-up and 70/88 (81% [0.70-0.87]) would recommend ONS to others. Hardware-related surgery was required in 44/88 (50%) participants in 112/122 (92%) events (0.35 person-year-1 [0.28-0.41]). We didn't find predictive factors for effectiveness. INTERPRETATION: ONS is a safe, well-tolerated and long-term effective treatment for MICCH. FUNDING: The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.</p
A prospective open label 2-8 year extension of the randomised controlled ICON trial on the long-term efficacy and safety of occipital nerve stimulation in medically intractable chronic cluster headache
BACKGROUND: We demonstrated in the randomised controlled ICON study that 48-week treatment of medically intractable chronic cluster headache (MICCH) with occipital nerve stimulation (ONS) is safe and effective. In L-ICON we prospectively evaluate its long-term effectiveness and safety. METHODS: ICON participants were enrolled in L-ICON immediately after completing ICON. Therefore, earlier ICON participants could be followed longer than later ones. L-ICON inclusion was stopped after the last ICON participant was enrolled in L-ICON and followed for ≥2 years by completing six-monthly questionnaires on attack frequency, side effects, subjective improvement and whether they would recommend ONS to others. Primary outcome was the change in mean weekly attack frequency 2 years after completion of the ICON study compared to baseline. Missing values for log-transformed attack-frequency were imputed for up to 5 years of follow-up. Descriptive analyses are presented as (pooled) geometric or arithmetic means and 95% confidence intervals. FINDINGS: Of 103 eligible participants, 88 (85%) gave informed consent and 73 (83%) were followed for ≥2 year, 61 (69%) ≥ 3 year, 33 (38%) ≥ 5 years and 3 (3%) ≥ 8.5 years. Mean (±SD) follow-up was 4.2 ± 2.2 years for a total of 370 person years (84% of potentially 442 years). The pooled geometric mean (95% CI) weekly attack frequency remained considerably lower after one (4.2; 2.8-6.3), two (5.1; 3.5-7.6) and five years (4.1; 3.0-5.5) compared to baseline (16.2; 14.4-18.3). Of the 49/88 (56%) ICON ≥50% responders, 35/49 (71%) retained this response and 15/39 (38%) ICON non-responders still became a ≥50% responder for at least half the follow-up period. Most participants (69/88; 78% [0.68-0.86]) reported a subjective improvement from baseline at last follow-up and 70/88 (81% [0.70-0.87]) would recommend ONS to others. Hardware-related surgery was required in 44/88 (50%) participants in 112/122 (92%) events (0.35 person-year-1 [0.28-0.41]). We didn't find predictive factors for effectiveness. INTERPRETATION: ONS is a safe, well-tolerated and long-term effective treatment for MICCH. FUNDING: The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.</p
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