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.

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.

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.

Phase-only modulation with a twisted nematic liquid crystal display by means of equi-azimuth polarization states.

The capability of a twisted nematic liquid crystal display to generate a set of equi-azimuth polarization states is used to achieve a phase-only modulation regime. For this purpose, a liquid crystal display followed by a quarter-wave plate is launched between two polarizers. Theoretical support is provided by means of the Jones matrix calculus and the Poincaré sphere representation. Laboratory results for a commercial liquid crystal display are presented. A phase modulation deep of 270 masculine is obtained at 514 nm with a residual intensity variation which is lower than 2.5 %.

[Incidence of influenza and influenza vaccine effectiveness in the 2004-2005 season]. / Incidencia de la gripe y efectividad de la vacuna antigripal en la temporada 2004-2005.

BACKGROUND: To quantify the incidence of flu in different groups of the population of Navarra in the 2004-2005 season, and to evaluate the effectiveness of anti-flu vaccination. METHODS: The analysis of influenza cases in the system of compulsory notificable diseases was complemented by the individualised notifications in the network of sentinel doctors that covers a population of 22,339 inhabitants. The coverage and effectiveness of the vaccine was studied. RESULTS: Vaccine coverage in (3)65 year olds reached 62%. The incidence of influenza was 42.6 cases per 1,000 inhabitants. It reached a maximum in mid-January, exceeding 750 weekly cases per 100,000 inhabitants and 1,900 cases per 100,000 children. The highest rate of influenza was observed in under-15 year olds (49.4 cases per 1,000 inhabitants) and the lowest in non-institutionalised (3)65 year olds (2.6 per 1,000 inhabitants), although it was higher in geriatric residences (62.1 per 1,000; p<0.0001). Seventy-nine percent of the cases from 5 to 64 years resulted in absenteeism from school or work. The flu virus was identified in 42/65 (65%) nasopharyngeal smears, 90% being influenza virus A(H3). The incidence of influenza was 3.08% in the unvaccinated and 0.45% in the vaccinated (p<0.001). The global effectiveness of the anti-flu vaccine was 65%, and in (3)65 years old it was 73%. CONCLUSION: Although its effectiveness is not total, the vaccine is the main measure for preventing influenza. The network of sentinel doctors provide useful information for the coordination of care and public health activities against flu.

Structure, binding and neutralization of VHSV with synthetic peptides.

The phosphatidylserine binding region p2 of VHSV was characterized and was shown to be involved with fusion. Synthetic peptides corresponding to this region interact with phospholipids by penetrating into the membrane and changing to a beta sheet configuration. Computer modeling of this region shows the possible ways by which the interaction with the membranes can succeed. Inhibitory peptides are presently being sought by studying possible interactions within heptad repeats located in other regions of the G protein of VHSV. The heptad repeat region that includes the phosphatidylserine binding domain p2 has been cloned and preliminary experiments show that under certain conditions, peptides from this region can inhibit VHSV infectivity.

In vitro inhibition of the replication of haemorrhagic septicaemia virus (VHSV) and African swine fever virus (ASFV) by extracts from marine microalgae.

We have screened for in vitro inhibition of viral replication with extracts from the following marine microalgae: Porphyridium cruentum, Phaeodactylum tricornutum, Tetraselmis suecica, Chlorella autotrophica, Dunaliella tertiolecta, Dunaliella bardawil, Isochrysis galbana, Isochrysis galbana var Tiso, Ellipsoidon sp. and Tetraselmis tetrathele. We have used as viral models two enveloped viruses of significant economic importance, the viral hemorrhagic septicemia virus (VHSV) of salmonid fish and the African swine fever virus (ASFV). The aqueous extracts from P. cruentum, C. autotrophica and Ellipsoidon sp., produced a significant inhibition of the in vitro replication of both viruses in a dose-dependent manner. That this inhibition could be due to sulfated polysaccharides was suggested because the same pattern of viral inhibition was obtained by using exocellular extracts from microalgae enriched in these compounds and/or dextran sulfate of high molecular weight. However, the inhibition of viral replication did not correlate with the percentage of sulfatation of the exocellular polysaccharides. Extracts from marine microalgae may have prophylactic utility against fish and mammalian viral diseases.

Antibody response to a fragment of the protein G of VHS rhabdovirus in immunised trout.

A fragment (called frg#11, amino acids, aa 56-110) of the protein G (pG) of viral haemorrhagic septicaemia virus (VHSV) was designed after previous results showed it to be recognised by approximately 40% of the trout immunised to VHSV [Dis. Aquat. Organ. 34 (1999) 167]. frg#11 was then cloned, expressed, purified and used to study the production of antibodies to its epitopes in trout immunised to VHSV. Anti-frg#11 trout antibodies could be detected in serum from individual trout surviving VHSV exposure, immunised by injection with purified VHSV or DNA-immunised with its pG gene whereas it was not detected in non-infected and non-immunised trout. The trout serum antibodies which reacted more strongly by ELISA using solid-phase frg#11 (continuous or linear epitopes on the sequence of the pG) had the lowest VHSV-neutralising activity (epitopes which are pG conformation-dependent). Because antibodies recognising continuous as well as conformation-dependent epitopes of the pG seem to be involved in protective trout immunological responses to VHSV, the estimation of anti-frg#11 antibodies could help to the dissection of the complex trout antibody response to VHSV infections. In addition, these preliminary results suggest that the determination of anti-frg#11 antibodies might also be used to complement in vitro viral neutralising assays which seem to be restricted to pG conformation-dependent epitopes.

Mapping of linear antibody epitopes of the glycoprotein of VHSV, a salmonid rhabdovirus.

Antibody linear epitopes of the glycoprotein G (gpG) of the viral haemorrhagic septicaemia virus (VHSV), a rhabdovirus of salmonids, were mapped by pepscan using overlapping 15-mer peptides covering the entire gpG sequence and ELISA with polyclonal and monoclonal murine and polyclonal trout antibodies. Among the regions recognized in the pepscan by the polyclonal antibodies (PAbs) were the previously identified phosphatidylserine binding heptad-repeats (Estepa & Coll 1996; Virology 216:60-70) and leucocyte stimulating peptides (Lorenzo et al. 1995; Virology 212:348-355). Among 17 monoclonal antibodies (MAbs), only 2 non-neutralizing MAbs, 110 (aa 139-153) and IP1H3 (aa 399-413), could be mapped to specific peptides in the pepscan of the gpG. Mapping of these MAbs was confirmed by immunoblotting with recombinant proteins and/or other synthetic peptides covering those sequences. None of the neutralizing MAbs tested reacted with any of the gpG peptides. Previously mapped MAb resistant mutants in the gpG did not coincide with any of the linear epitopes defined by the pepscan strategy, suggesting the complementarity of the 2 methods for the identification of antibody recognition sites.

[The effects of cholestyramine on pancreatic secretion]. / Efectos de la colestiramina sobre la secreción pancreática.

The objective was to evaluate the effect of biliary salt depletion on morphology and function of the exocrine pancreas. Cholestyramine (15 g/day) was given during fifteen days to male Wistar rats in order to evaluate changes in pancreas weight as well as in enzymatic content of pancreatic tissue and duodenal juice (amylase, lipase and trypsinogen); in duodenal juice, bile salt concentration was also measured; Moreover ultrastructure of the exocrine pancreas was studied. Our results show an increase in pancreas weight in rats treated with cholestyramine, with a significant increase of amylase (p < 0.05) and trypsinogen in pancreatic tissue (p < 0.01), and of lipase in duodenal juice (p < 0.05). Ultrastructural changes were absent. It is concluded that cholestyramine, probably through a bile salt depletion, stimulates pancreatic function and growth, as well as lipase secretion.

[Outcome at year after rehabilitation of proximal femur fracture in older than 84 years]. / Resultados al año de la rehabilitación tras fractura de fémur proximal en mayores de 84 años.

OBJECTIVE: To evaluate rehabilitation outcomes at discharge and at year patients older 85 years admitted to functional treatment after hip fracture. METHOD: A prospective study of inpatients admitted after hip fracture to medium-stay geriatric unit between May 2000 and September 2002. Baseline, clinical variables (location of fracture, serum albumin and Charlson comorbidity index), functional status assessed by Barthel Index, mobility by Physical Red Cross Scale and cognitive status by Pfeiffer questionnaire. Functional status, mobility, institutionalization and death was evaluated at discharge and by phone interview at years after discharge. RESULTS: 116 patients were studied (42% with 85 years and older, 85% women). After multivariable logistic analysis, age older than 84 years did not appear as a factor related to functional dependence or institutionalization at discharge or one year after. Indeed, oldest old age was not related with death or institutionalization and mobility dependence one year after. In the other hand, the presence of cognitive impairment at admission and functional impairment before hip fracture were independently variable associated to the presence of poor outcome at discharge and one year after. CONCLUSIONS: Oldest old age does not appear as a independent risk factor of poor outcomes after rehabilitation of hip fracture when other related clinical, functional and mental factors are considered.

[Modifications of the enzymatic content and morphology of the exocrine pancreas of rats with experimental hepatic cirrhosis induced by thioacetamide]. / Modificaciones del contenido enzimático y de la morfología del páncreas exocrino de rata con cirrosis hepática experimental inducida por tioacetamida.

In order to assess the experimental level of enzymatic content in exocrine pancreas of cirrhotic rats, cirrhosis was induced with administration of thioacetamide (50 mg/kg) during ten weeks to male Wistar rats with an initial average weight of 350 g. Contents of amylase, lipase and trypsinogen were determined in pancreatic tissues and amylase, lipase and biliary salts in duodenal juice obtained by cannulation and perfusion with physiologic serum. A higher presence of trypsinogen and amylase was detected in pancreatic tissues, and of lipase in the duodenal juice, with a trend, although insignificant, towards a decrease in biliary salts among the cirrhotic group. No changes were observed in the morphologic study. The hypothesis that a deficit of biliary salts in experimental cirrhosis could be responsible of the enzymatic increase in the pancreatic tissue and, in particular, of the selective excretion of lipase, is discussed.