Discovery of Gamma Rays from the Quiescent Sun with HAWC.

We report the first detection of a TeV γ-ray flux from the solar disk (6.3σ), based on 6.1 years of data from the High Altitude Water Cherenkov (HAWC) observatory. The 0.5-2.6 TeV spectrum is well fit by a power law, dN/dE=A(E/1 TeV)^{-γ}, with A=(1.6±0.3)×10^{-12} TeV^{-1} cm^{-2} s^{-1} and γ=3.62±0.14. The flux shows a strong indication of anticorrelation with solar activity. These results extend the bright, hard GeV emission from the disk observed with Fermi-LAT, seemingly due to hadronic Galactic cosmic rays showering on nuclei in the solar atmosphere. However, current theoretical models are unable to explain the details of how solar magnetic fields shape these interactions. HAWC's TeV detection thus deepens the mysteries of the solar-disk emission.

Chronic rhinosinusitis is associated with prolonged SARS-CoV-2 RNA shedding in upper respiratory tract samples: A case-control study.

BACKGROUND: SARS-CoV-2, the COVID-19 causative agent, has infected millions of people and killed over 1.6 million worldwide. A small percentage of cases persist with prolonged positive RT-PCR on nasopharyngeal swabs. The aim of this study was to determine risk factors for prolonged viral shedding amongst patient's basal clinical conditions. METHODS: We have evaluated all 513 patients attended in our hospital between 1 March and 1 July. We have selected all 18 patients with prolonged viral shedding and compared them with 36 sex-matched randomly selected controls. Demographic, treatment and clinical data were systematically collected. RESULTS: Global median duration of viral clearance was 25.5 days (n = 54; IQR, 22-39.3 days), 48.5 days in cases (IQR 38.7-54.9 days) and 23 days in controls (IQR 20.2-25.7), respectively. There were not observed differences in demographic, symptoms or treatment data between groups. Chronic rhinosinusitis and atopy were more common in patients with prolonged viral shedding (67%) compared with controls (11% and 25% respectively) (P < 0.001 and P = 0.003). The use of inhaled corticosteroids was also more frequent in case group (P = 0.007). Multivariate analysis indicated that CRS (odds ratio [OR], 18.78; 95% confidence interval [95%CI], 3.89-90.59; P < 0.001) was independently associated with prolonged SARS-CoV-2 RNA shedding in URT samples, after adjusting for initial PCR Ct values. CONCLUSION: We found that chronic rhinosinusitis and atopy might be associated with increased risk of prolonged viral shedding. If confirmed in prospective trials, this finding might have clinical implications for quarantine duration due to increased risk of pandemic spread.

Reduction in mortality associated with secondary cytomegalovirus prophylaxis after solid organ transplantation.

BACKGROUND: Cytomegalovirus (CMV) is the most important viral pathogen in solid organ transplant (SOT) recipients. The role of secondary CMV prophylaxis in this population remains unclear. METHODS: Retrospective cohort study in a single center. SOT recipients treated for CMV infection from 2007 to 2014 were studied to determine the efficacy and safety of secondary prophylaxis and its impact on graft loss and mortality. The outcome variable was CMV replication in the first 3 months after the end of therapy. Secondary variables were crude mortality and graft lost censored at 5 years after transplantation. Propensity score for the use of secondary prophylaxis was used to control selection bias. RESULTS: Of the 126 treated patients, 103 (83.1%) received CMV secondary prophylaxis. CMV relapse occurred in 44 (35.5%) patients. The use of secondary prophylaxis was not associated with fewer relapses (34.0% in patients with prophylaxis vs 42.9% in those without prophylaxis, P = .29). After a mean follow-up of 32.1 months, graft loss was not different between both groups but patient mortality was significantly lower in patients who received secondary prophylaxis (5.8% vs 28.6%, P = .003). CONCLUSION: Secondary prophylaxis did not prevent CMV infection relapse but it was associated with improved patient survival.

Monitoring Glycan-Protein Interactions by NMR Spectroscopic Analysis: A Simple Chemical Tag That Mimics Natural CH-π Interactions.

Detection of molecular recognition processes requires robust, specific, and easily implementable sensing methods, especially for screening applications. Here, we propose the difluoroacetamide moiety (an acetamide bioisoster) as a novel tag for detecting by NMR analysis those glycan-protein interactions that involve N-acetylated sugars. Although difluoroacetamide has been used previously as a substituent in medicinal chemistry, here we employ it as a specific sensor to monitor interactions between GlcNAc-containing glycans and a model lectin (wheat germ agglutinin). In contrast to the widely employed trifluoroacetamide group, the difluoroacetamide tag contains geminal (1) H and (19) F atoms that allow both (1) H and (19) F NMR methods for easy and robust detection of molecular recognition processes involving GlcNAc- (or GalNAc-) moieties over a range of binding affinities. The CHF2 CONH- moiety behaves in a manner that is very similar to that of the natural acetamide fragment in the involved aromatic-sugar interactions, providing analogous binding energy and conformations, whereas the perfluorinated CF3 CONH- analogue differs more significantly.

Compromiso de la atención primaria ante la violencia de género. ¿Hemos superado el reto? / Commitment of primary care to gender violence. Have we met the challenge?

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Cooperative hydrogen bonding in glyco-oligoamides: DNA minor groove binders in aqueous media.

A strategy to create cooperative hydrogen-bonding centers by using strong and directional intramolecular hydrogen-bonding motifs that can survive in aqueous media is presented. In particular, glyco-oligoamides, a family of DNA minor groove binders, with cooperative and non-cooperative hydrogen-bonding donor centers in the carbohydrate residues have been designed, synthesized, and studied by means of NMR spectroscopy and molecular modeling methods. Indeed, two different sugar moieties, namely, ß-D-Man-Py-γ-Py-Ind (1; Ind=indole, Man=mannose, Py=pyrrole) and ß-D-Tal-Py-γ-Py-Ind (2; Tal=talose), were chosen according to our design. These sugar molecules should present one- or two-directional intramolecular hydrogen bonds. The challenge has been to study the conformation of the glyco-oligoamides at low temperature in physiological media by detecting the exchangeable protons (amide NH and OH resonances) by means of NMR spectroscopic analysis. In addition, two more glyco-oligoamides with non-cooperative hydrogen-bonding centers, that is, ß-D-Glc-Py-γ-Py-Ind (3; Glc=glucose), ß-D-Gal-Py-γ-Py-Ind (4; Gal=galactose), and the model compounds ß-D-Man-Py-NHAc (5) and ß-D-Tal-Py-NHAc (6) were synthesized and studied for comparison. We have demonstrated the existence of directional intramolecular hydrogen bonds in 1 and 2 in aqueous media. The unexpected differences in terms of stabilization of the intramolecular hydrogen bonds in 1 and 2 relative to 5 and 6 promoted us to evaluate the influence of CH-π interactions on the establishment of intramolecular hydrogen bonds by using computational methods. Initial binding studies of 1 and 2 with calf-thymus DNA and poly(dA-dT)2 by NMR spectroscopic analysis and molecular dynamics simulations were also carried out. Both new sugar-oligoamides are bound in the minor groove of DNA, thus keeping a stable hairpin structure, as in the free state, in which both intramolecular hydrogen-bonding and CH-π interactions are present.

Vaccine effectiveness in preventing laboratory-confirmed influenza in Navarre, Spain: 2013/14 mid-season analysis.

We estimate mid-2013/14 season vaccine effectiveness (VE) of the influenza trivalent vaccine in Navarre, Spain. Influenza-like illness cases attended in hospital (n=431) and primary healthcare (n=344) were included. The overall adjusted VE in preventing laboratory-confirmed influenza was 24% (95% CI: -14 to 50). The VE was 40% (95% CI: -12 to 68) against influenza A(H1)pdm09 and 13% (95% CI: -36 to 45) against influenza A(H3). These results suggest a moderate preventive effect against influenza A(H1)pdm09 and low protection against influenza A(H3).

Early estimates of influenza vaccine effectiveness in Navarre, Spain: 2012/13 mid-season analysis.

We present estimates of influenza vaccine effectiveness (VE) in Navarre, Spain, in the early 2012/13 season, which was dominated by influenza B. In a population-based cohort using electronic records from physicians, the adjusted VE in preventing influenzalike illness was 32% (95% confidence interval (CI): 15 to 46). In a nested test-negative case-control analysis the adjusted VE in preventing laboratory-confirmed influenza was 86% (95% CI: 45 to 96). These results suggest a high protective effect of the vaccine.

Caracterización de la pandemia de gripe A H1N1 2009 en Navarra / The 2009 H1N1 influenza pandemic in Navarre, Spain

Fundamento. Describir la actividad gripal durante la pandemia de 2009-2010 en Navarra y compararla con la de temporadas anteriores. Métodos. Se han analizado los casos de gripe notificados en atención primaria y todas las confirmaciones virológicas realizadas en pacientes de atención primaria y en hospitales de Navarra entre las semanas 21 de 2009 y 20 de 2010. Resultados. El virus de la gripe A (H1N1) 2009 se detectó en Navarra entre las semana 23 de 2009 a la 2 de 2010, periodo en el que se registraron 39 casos con diagnóstico médico de síndrome gripal por 1.000 habitantes. El umbral epidémico se superó en dos periodos, con un pico en julio y otro mayor en noviembre. La mayor incidencia se alcanzó en niños de 5 a 14 años (121 por mil), seguidos por el grupo de menores de 5 años. Se produjeron 224 hospitalizaciones (36 por 100.000 habitantes) con confirmación de gripe A H1N1 2009, 8% de ellos requirieron ingreso en unidades de cuidados intensivos y hubo cuatro defunciones (0,6 por 100.000 habitantes). La tasa de hospitalizaciones fue mayor en niños menores de 5 años (163 por 100.000 habitantes), mientras que la probabilidad de derivación a cuidados intensivos aumentó con la edad. Conclusión. A pesar de no haber dispuesto de una vacuna específica hasta que la temporada estaba muy avanzada, el virus de gripe A (H1N1) 2009 produjo una onda gripal en rangos similares a los de otras temporadas y su repercusión en hospitalizaciones y casos graves fue moderada (AU)

Background. To describe influenza activity during the2009-2010 pandemic in Navarre and compare it to previous seasons. Methods. An analysis was made of all influenza-like illness cases reported in primary care and all the virological confirmations made in patients in primary care and in hospitals of Navarre between week 21 of 2009 and week 20 of 2010. Results. Influenza 2009 H1N1 virus was detected in Navarre between week 23 of 2009 and week 2 of 2010, a period when 39 medically diagnosed cases of influenza-like illness per 1,000 inhabitants were registered. The epidemicthres hold was surpassed in two periods, with a peak in July and a greater one in November. The greatest incidence was reached in children aged between 5 and 14 years (121 per thousand), followed by the group of under fives.There were 224 hospitalisations (36 per 100,000 inhabitants)with confirmation of influenza 2009 H1N1 virus, 8% of whom required admission to intensive care units and there were four deaths (0.6 per 100,000 inhabitants). The rate of hospitalisation was greater amongst children under five (163 per 100,000 inhabitants), while the probability of referral to intensive care increased with age. Conclusion. In spite of not having a specific vaccine available until the season was very well advanced, influenza 2009 H1N1 virus produced a wave of cases with similar incidence to those of other seasons and its repercussion in hospitalizations and serious cases was moderate (AU)

[The 2009 H1N1 flu pandemic in Navarre, Spain]. / Caracterización de la pandemia de gripe a H1N1 2009 en Navarra.

BACKGROUND: To describe flu activity during the 2009-2010 pandemic in Navarre and compare it to previous seasons. METHODS: An analysis was made of all flu cases reported in primary care and all the virological confirmations made in patients in primary care and in hospitals of Navarre between week 21 of 2009 and week 20 of 2010. RESULTS: Influenza A (H1N1) Virus 2009 was detected in Navarre between week 23 of 2009 and week 2 of 2010, a period when 39 medically diagnosed cases of flu syndrome per 1,000 inhabitants were registered. The epidemic threshold was surpassed in two periods, with a peak in July and a greater one in November. The greatest incidence was reached in children aged between 5 and 14 years (121 per thousand), followed by the group of under fives. There were 224 hospitalisations (36 per 100,000 inhabitants) with confirmation of Influenza A (H1N1) Virus 2009, 8% of whom required admission to intensive care units and there were four deaths (0.6 per 100,000 inhabitants). The rate of hospitalisation was greater amongst children under five (163 per 100,000 inhabitants), while the probability of referral to intensive care increased with age. CONCLUSION: In spite of not having a specific vaccine available until the season was very well advanced, Influenza A (H1N1)Virus 2009 produced a flu wave with similar levels to those of other seasons and its repercussion in hospitalisations and serious cases was moderate.

The KCNQ1 (Kv7.1) COOH terminus, a multitiered scaffold for subunit assembly and protein interaction.

The Kv7 subfamily of voltage-dependent potassium channels, distinct from other subfamilies by dint of its large intracellular COOH terminus, acts to regulate excitability in cardiac and neuronal tissues. KCNQ1 (Kv7.1), the founding subfamily member, encodes a channel subunit directly implicated in genetic disorders, such as the long QT syndrome, a cardiac pathology responsible for arrhythmias. We have used a recombinant protein preparation of the COOH terminus to probe the structure and function of this domain and its individual modules. The COOH-terminal proximal half associates with one calmodulin constitutively bound to each subunit where calmodulin is critical for proper folding of the whole intracellular domain. The distal half directs tetramerization, employing tandem coiled-coils. The first coiled-coil complex is dimeric and undergoes concentration-dependent self-association to form a dimer of dimers. The outer coiled-coil is parallel tetrameric, the details of which have been elucidated based on 2.0 A crystallographic data. Both coiled-coils act in a coordinate fashion to mediate the formation and stabilization of the tetrameric distal half. Functional studies, including characterization of structure-based and long QT mutants, prove the requirement for both modules and point to complex roles for these modules, including folding, assembly, trafficking, and regulation.

gem-Difluoro-carbasugars, the cases of mannopyranose and galactopyranose.

5a-Difluoro-5a-carbamannopyranose (gem-difluoro-carbamannopyranose) and 5a-difluoro-5a-carbagalactopyranose (gem-difluoro-carbagalactopyranose), close congeners of their respective natural sugars, in which the endocyclic oxygen atom has been replaced by a gem-difluoromethylene group, were synthesized from D-mannose and D-galactose, using a rearrangement strategy.

[Prognostic factors of functional recovery in very elderly stroke patients. A one-year follow-up study]. / Factores pronósticos de recuperación funcional en pacientes muy ancianos con ictus. Estudio de seguimiento al año.

INTRODUCTION: Although an advanced age is a factor associated to a poorer functional prognosis following a stroke, the capacity for recovery can be determined by other intercurrent clinical, functional and mental factors. AIM: To evaluate the factors that determine the functional prognosis on discharge of very elderly patients who were admitted to hospital for their functional recovery after suffering a stroke. PATIENTS AND METHODS: We conducted a longitudinal observational study of 168 patients over 65 years of age, who were hospitalised consecutively over a 15-month period. On admission, data concerning a number of clinical, neurological, functional and mental variables were collected. On being discharged from hospital their functional situation (Barthel index) and institutionalisation were evaluated. RESULTS: The 48 patients aged 85 and above presented a lower degree of overall and relative functional recovery on discharge from hospital. Nevertheless, 52% had gained more than 20 points on the Barthel index on being discharged with respect to their score when they were admitted; on discharge 44% had recovered over 50% of the functional loss they had suffered following the stroke. On including the other basal variables in a logistic regression analysis, a very advanced age was associated in an independent manner to a greater risk of being institutionalised, but not to a poorer functional prognosis at discharge. Severe functional impairment on admission and post-stroke depression were the factors that were independently associated to moderate-severe disability on admission; in addition, the more severe the neurological consequences were, the lower the level of functional recovery was. CONCLUSIONS: The capacity for functional recovery in very elderly stroke patients is mainly determined by the degree of functional and neurological repercussion. The functional prognosis should be individualised according to these factors, regardless of the age.

Factores pronósticos de recuperación funcional en pacientes muy ancianos con ictus. Estudio de seguimiento al año / Prognostic factors of functional recovery in very elderly stroke patients. A one-year follow-up study

Introducción. Aunque la edad avanzada es un factor asociado a un peor pronóstico funcional tras un ictus, la capacidad de recuperación puede venir determinada por otros factores clínicos, funcionales y mentales intercurrentes. Objetivo. Evaluar los factores que determinan el pronóstico funcional al alta de pacientes muy ancianos ingresados para recuperación funcional tras sufrir un ictus. Pacientes y métodos. Estudio longitudinal de observación de 168 pacientes mayores de 65 años, ingresados consecutivamente durante un período de 15 meses. A su ingreso se recogieron variables clínicas, neurológicas, funcionales y mentales. Al alta se evaluó la situación funcional (índice de Barthel) y la institucionalización. Resultados. Los 48 pacientes de 85 y más años presentaban una menor recuperación funcional global y relativa al alta; pese a ello, el 52% ganaban más de 20 puntos en el índice de Barthel al alta con relación al del ingreso y un 44% recuperaban al alta más del 50% de la pérdida funcional sufrida tras el ictus. Al incluir el resto de variables basales en un análisis de regresión logística, la edad muy avanzada se asociaba de forma independiente a mayor riesgo de institucionalización, pero no a peor pronóstico funcional al alta. El deterioro funcional grave al ingreso y la depresión postictus eran los factores independientemente asociados a la discapacidad moderada-grave al alta y la mayor gravedad neurológica se relacionaba con una menor recuperación funcional y mayor tasa de institucionalización. Conclusiones. La capacidad de recuperación funcional en pacientes con ictus muy ancianos viene determinada principalmente por el grado de repercusión funcional y neurológica. Es necesario individualizar el pronóstico funcional por estos factores, independientemente de la edad

Introduction. Although an advanced age is a factor associated to a poorer functional prognosis following a stroke, the capacity for recovery can be determined by other intercurrent clinical, functional and mental factors. Aim. To evaluate the factors that determine the functional prognosis on discharge of very elderly patients who were admitted to hospital for their functional recovery after suffering a stroke. Patients and methods. We conducted a longitudinal observational study of 168 patients over 65 years of age, who were hospitalised consecutively over a 15-month period. On admission, data concerning a number of clinical, neurological, functional and mental variables were collected. On being discharged from hospital their functional situation (Barthel index) and institutionalisation were evaluated. Results. The 48 patients aged 85 and above presented a lower degree of overall and relative functional recovery on discharge from hospital. Nevertheless, 52% had gained more than 20 points on the Barthel index on being discharged with respect to their score when they were admitted; on discharge 44% had recovered over 50% of the functional loss they had suffered following the stroke. On including the other basal variables in a logistic regression analysis, a very advanced age was associated in an independent manner to a greater risk of being institutionalised, but not to a poorer functional prognosis at discharge. Severe functional impairment on admission and post-stroke depression were the factors that were independently associated to moderate-severe disability on admission; in addition, the more severe the neurological consequences were, the lower the level of functional recovery was. Conclusions. The capacity for functional recovery in very elderly stroke patients is mainly determined by the degree of functional and neurological repercussion. The functional prognosis should be individualised according to these factors, regardless of the age

[Protocol to evaluate the effectiveness of a consciousness-raising and training intervention for primary care professionals, in order to improve detection of domestic violence (ISFVIDAP)]. / Protocolo para la evaluación de la efectividad de una intervención sensibilizadora y formativa en profesionales de atención primaria para la mejora de la detección de la violencia doméstica (ISFVIDAP).

OBJECTIVE: To evaluate the effectiveness of an intervention aimed at primary care physicians and nurses to improve the detection of domestic violence. DESIGN: Community intervention study with control, randomized in clusters, pragmatic, open, and with parallel groups. SETTING: Primary care centres in Spain. POPULATION: Primary care physicians and nurses from the entire country who agree to participate in the study. UNIT OF ANALYSIS: The basic care team (BCT) of doctor and nurse looking after a list is the unit of analysis for evaluating the number of cases detected; and their clinical records are the units of analysis for evaluating recorded cases (suspicion and/or confirmation of mistreatment). SAMPLE SIZE: Sixty eight BCT in each group (136 in the 2 groups) and 1700 clinical records per group (25 per BCT). Altogether, they will cover some 130,000 women of 14 and over. INTERVENTION: A short training programme with homogeneous training contents, aimed at raising the awareness of health professionals and teaching them how to identify risk factors, situations of special vulnerability and alarm signals. The programme also aims to provide health professionals with tools to make the clinical interview easier, when they suspect mistreatment and how to tackle a case once it is detected. MEASUREMENTS: The main measurement will be the mean variation between intervention and control groups in the number of cases of domestic violence detected during the study, through specific recording and mean variation between the initial and final variations in each group. ANALYSIS: A weighted student's t test or, if covariates need to be adjusted, a regression analysis will be used for comparison. All analyses will be based on intention to treat.