Fatigue in Women with Fibromyalgia: A Gene-Physical Activity Interaction Study

Fatigue is a cardinal symptom in fibromyalgia. Fatigue is assumed to be the result of genetic susceptibility and environmental factors. We aimed at examining the role of genetic susceptibility for fatigue in southern Spanish women with fibromyalgia, by looking at single nucleotide polymorphisms in 34 fibromyalgia candidate-genes, at the interactions between genes, and at the gene-physical activity interactions. We extracted DNA from saliva of 276 fibromyalgia women to analyze gene-polymorphisms. Accelerometers registered physical activity and sedentary behavior. Fatigue was assessed with the Multidimensional Fatigue Inventory. Based on the Bonferroni's and False Discovery Rate values, we found that the genotype of the rs4453709 polymorphism (sodium channel protein type 9 subunit alpha, SCN9A, gene) was related to reduced motivation (AT carriers showed the highest reduced motivation) and reduced activity (AA carriers showed the lowest reduced activity). Carriers of the heterozygous genotype of the rs1801133 (methylene tetrahydrofolate reductase, MTHFR, gene) or rs4597545 (SCN9A gene) polymorphisms who were physically active reported lower scores on fatigue compared to their inactive counterparts. Highly sedentary carriers of the homozygous genotype of the rs7607967 polymorphism (AA/GG genotype; SCN9A gene) presented more reduced activity (a dimension of fatigue) than those with lower levels of sedentary behavior. Collectively, findings from the present study suggest that the contribution of genetics and gene-physical activity interaction to fatigue in fibromyalgia is modest

A Model for the Development of the Rhizobial and Arbuscular Mycorrhizal Symbioses in Legumes and Its Use to Understand the Roles of Ethylene in the Establishment of these two Symbioses

We propose a model depicting the development of nodulation and arbuscular mycorrhizae. Both processes are dissected into many steps, using Pisum sativum L. nodulation mutants as a guideline. For nodulation, we distinguish two main developmental programs, one epidermal and one cortical. Whereas Nod factors alone affect the cortical program, bacteria are required to trigger the epidermal events. We propose that the two programs of the rhizobial symbiosis evolved separately and that, over time, they came to function together. The distinction between these two programs does not exist for arbuscular mycorrhizae development despite events occurring in both root tissues. Mutations that affect both symbioses are restricted to the epidermal program. We propose here sites of action and potential roles for ethylene during the formation of the two symbioses with a specific hypothesis for nodule organogenesis. Assuming the epidermis does not make ethylene, the microsymbionts probably first encounter a regulatory level of ethylene at the epidermis–outermost cortical cell layer interface. Depending on the hormone concentrations there, infection will either progress or be blocked. In the former case, ethylene affects the cortex cytoskeleton, allowing reorganization that facilitates infection; in the latter case, ethylene acts on several enzymes that interfere with infection thread growth, causing it to abort. Throughout this review, the difficulty of generalizing the roles of ethylene is emphasized and numerous examples are given to demonstrate the diversity that exists in plants

Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%

Detection of persistent VHE gamma-ray emission from PKS 1510-089 by the MAGIC telescopes during low states between 2012 and 2017

PKS 1510-089 is a flat spectrum radio quasar strongly variable in the optical and GeV range. To date, very high-energy (VHE, > 100 GeV) emission has been observed from this source either during long high states of optical and GeV activity or during short flares. Aims. We search for low-state VHE gamma-ray emission from PKS 1510-089. We characterize and model the source in a broadband context, which would provide a baseline over which high states and flares could be better understood. Methods. PKS 1510-089 has been monitored by the MAGIC telescopes since 2012. We use daily binned Fermi-LAT flux measurements of PKS 1510-089 to characterize the GeV emission and select the observation periods of MAGIC during low state of activity. For the selected times we compute the average radio, IR, optical, UV, X-ray, and gamma-ray emission to construct a low-state spectral energy distribution of the source. The broadband emission is modeled within an external Compton scenario with a stationary emission region through which plasma and magnetic fields are flowing. We also perform the emission-model-independent calculations of the maximum absorption in the broad line region (BLR) using two different models. Results. The MAGIC telescopes collected 75 hr of data during times when the Fermi-LAT flux measured above 1 GeV was below 3? × 10 -8 ? cm -2 ? s -1 , which is the threshold adopted for the definition of a low gamma-ray activity state. The data show a strongly significant (9.5¿) VHE gamma-ray emission at the level of (4.27 ± 0.61 stat ) × 10 -12 ? cm -2 ? s -1 above 150 GeV, a factor of 80 lower than the highest flare observed so far from this object. Despite the lower flux, the spectral shape is consistent with earlier detections in the VHE band. The broadband emission is compatible with the external Compton scenario assuming a large emission region located beyond the BLR. For the first time the gamma-ray data allow us to place a limit on the location of the emission region during a low gamma-ray state of a FSRQ. For the used model of the BLR, the 95% confidence level on the location of the emission region allows us to place it at a distance > 74% of the outer radius of the BLR. © ESO 2018.The financial support of the German BMBF and MPG, the Italian INFN and INAF, the Swiss National Fund SNF, the ERDF under the Spanish MINECO (FPA2015-69818-P, FPA2012-36668, FPA2015-68378-P, FPA2015-69210-C6-2-R, FPA2015-69210-C6-4-R, FPA2015-69210-C6-6-R, AYA2015-71042-P, AYA2016-76012-C3-1-P, ESP2015-71662-C2-2-P, CSD2009-00064), and the Japanese JSPS and MEXT is gratefully acknowledged. This work was also supported by the Spanish Centro de Exce-lencia “Severo Ochoa” SEV-2012-0234 and SEV-2015-0548, and Unidad de Excelencia “María de Maeztu” MDM-2014-0369, by the Croatian Science Foundation (HrZZ) Project IP-2016-06-9782 and the University of Rijeka Project 13.12.1.3.02, by the DFG Collaborative Research Centers SFB823/C4 and SFB876/C3, the Polish National Research Centre grant UMO-2016/22/M/ST9/00382, and by the Brazilian MCTIC, CNPq and FAPERJ. IA acknowledges support from a Ramón y Cajal grant of the Ministerio de Economía, Industria, y Competitividad (MINECO) of Spain. Acquisition and reduction of the POLAMI and MAPCAT data was supported in part by MINECO through grants AYA2010-14844, AYA2013-40825-P, and AYA2016-80889-P, and by the Regional Government of Andalucía through grant P09-FQM-4784.Peer Reviewe

The European Solar Telescope

The European Solar Telescope (EST) is a project aimed at studying the magnetic connectivity of the solar atmosphere, from the deep photosphere to the upper chromosphere. Its design combines the knowledge and expertise gathered by the European solar physics community during the construction and operation of state-of-the-art solar telescopes operating in visible and near-infrared wavelengths: the Swedish 1m Solar Telescope, the German Vacuum Tower Telescope and GREGOR, the French Télescope Héliographique pour l'Étude du Magnétisme et des Instabilités Solaires, and the Dutch Open Telescope. With its 4.2 m primary mirror and an open configuration, EST will become the most powerful European ground-based facility to study the Sun in the coming decades in the visible and near-infrared bands. EST uses the most innovative technological advances: the first adaptive secondary mirror ever used in a solar telescope, a complex multi-conjugate adaptive optics with deformable mirrors that form part of the optical design in a natural way, a polarimetrically compensated telescope design that eliminates the complex temporal variation and wavelength dependence of the telescope Mueller matrix, and an instrument suite containing several (etalon-based) tunable imaging spectropolarimeters and several integral field unit spectropolarimeters. This publication summarises some fundamental science questions that can be addressed with the telescope, together with a complete description of its major subsystems

Observation of inverse Compton emission from a long γ-ray burst.

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Energy dependence of ϕ meson production at forward rapidity in pp collisions at the LHC

The production of $\phi$ mesons has been studied in pp collisions at LHC energies with the ALICE detector via the dimuon decay channel in the rapidity region $2.5< y < 4$. Measurements of the differential cross section $\mathrm{d}^2\sigma /\mathrm{d}y \mathrm{d}p_{\mathrm {T}}$ are presented as a function of the transverse momentum ($p_{\mathrm {T}}$) at the center-of-mass energies $\sqrt{s}=5.02$, 8 and 13 TeV and compared with the ALICE results at midrapidity. The differential cross sections at $\sqrt{s}=5.02$ and 13 TeV are also studied in several rapidity intervals as a function of $p_{\mathrm {T}}$, and as a function of rapidity in three $p_{\mathrm {T}}$ intervals. A hardening of the $p_{\mathrm {T}}$-differential cross section with the collision energy is observed, while, for a given energy, $p_{\mathrm {T}}$ spectra soften with increasing rapidity and, conversely, rapidity distributions get slightly narrower at increasing $p_{\mathrm {T}}$. The new results, complementing the published measurements at $\sqrt{s}=2.76$ and 7 TeV, allow one to establish the energy dependence of $\phi$ meson production and to compare the measured cross sections with phenomenological models. None of the considered models manages to describe the evolution of the cross section with $p_{\mathrm {T}}$ and rapidity at all the energies.publishedVersio

Registro ACESUR: atención de pacientes adultos con crisis epilépticas en servicios de urgencias: diferencias entre primer episodio y recurrencia

Objetivo. Describir las características y la atención recibida de pacientes adultos que consultan por crisis epiléptica (CE) en los servicios de urgencias hospitalarios (SUH), diferenciando entre primera crisis y recurrencia en epiléptico conocido. Método. ACESUR es un registro observacional de cohortes multipropósito, prospectivo y multicéntrico con un muestreo sistemático, los días pares de febrero y julio alternando con los impares de abril y octubre de 2017. Se incluyeron pacientes 18 años con diagnóstico de CE en los SUH. Se recogieron variables clínico-asistenciales de la visita índice de pacientes, distinguiendo entre primera CE y recurrencia en epiléptico. Resultados. El registro ACESUR recogió a 664 pacientes procedentes de 18 SUH españoles, 229 (34, 5%) con primera CE y 435 (65, 5%) con CE recurrentes. Los pacientes con primera CE fueron de mayor edad (p < 0, 001), presentaron motivos de consulta distintos (p < 0, 001) y requirieron más traslados en ambulancia (p < 0, 001). La atención recibida en el SUH fue diferente, en pacientes con primera CE se solicitó con mayor probabilidad una prueba complementaria específica (OR ajustada = 13, 94; IC95%:7, 29-26, 7; p < 0, 001) y se necesitó mayor hospitalización o estancia prolongada en el SUH (OR ajustada = 1, 69; IC95%:1, 11-2, 58; p = 0, 015). No hubo diferencias en cuanto al tratamiento farmacológico en fase aguda ni preventivo (OR ajustada = 1, 40; IC95%:0, 94-2, 09; p = 0, 096). Se inició tratamiento con fármacos antiepiépticos (FAE) en 100 pacientes (43, 7%) tras primera CE y se reinició o modificó añadiendo nuevo FAE en 142 pacientes (32, 6%) con CE recurrentes. Conclusiones. Las características clínicas y la atención recibida de pacientes adultos con primera CE en SUH en España difieren de las recurrencias en epiléptico conocido. Objective. To describe the characteristics of care received by patients who come to the emergency department with a first epileptic seizure versus a recurrent seizure in a patient with diagnosed epilepsy. Methods. ACESUR (Acute Epileptic Seizures in the Emergency Department) is a prospective multicenter, multipurpose registry of cases obtained by systematic sampling on even days in February and July 2017 and on odd days in April and October 2017. Patients were aged 18 years or older and had an emergency department diagnosis of epileptic seizure. We recorded clinical variables and details related to care given during each patient''s visit, including whether the event was a first or recurrent seizure. Results. A total of 664 patients attended by 18 Spanish emergency departments were entered into the ACESUR registry. Two hundred twenty-nine (34.5%) were first seizures and 435 (65.5%) were recurrences. Patients who were attended for first seizures were older, consulted for a wider variety of reasons, and were transported in ambulances (P<.001, all comparisons). Care received differed between patients with first seizures versus recurrent seizures. Specific complementary testing was more likely in patients with first seizures (adjusted odds ratio [aOR], 13.94; 95% CI, 29-26.7; P<.001), and they were more often hospitalized or stayed longer in the emergency department, (aOR, 1.69; 95% CI, 1.11-2.58; P=.015). Pharmacologic treatment did not differ between the groups, either in the acute phase or for prevention (aOR, 1.40; 95% CI, 0.94-2.09; P=.096). Antiepileptic drugs were given to 100 patients (43.7%) after a first seizure and were restarted or changed in 142 patients with recurrent seizure (32.6%). Conclusions. The clinical characteristics of adults attended for a first epileptic seizure differ from those of patients with diagnosed epilepsy who were attended for recurrent seizures in Spain. The care received also differs