[Challenges and initiatives in the prevention of healthcare associated infections: Expert consensus study]. / Retos e iniciativas en la prevención de las infecciones relacionadas con la asistencia sanitaria: estudio de consenso de expertos.

INTRODUCTION: The objective of the project was to identify new strategies, agreed upon by experts, that help reduce the prevalence of Health Care Related Infections (HAIs) given the increase in their prevalence as a result of the pandemic and improve patient safety. MATERIAL AND METHODS: The project was developed in three phases. The first two are framed in a sequential explanatory mixed model. Phase 1 consisted of a quantitative study (anonymous survey) to find out the perception of healthcare professionals about HAIs, risk factors, preventive measures, protocols, disinfection products and approaches. Phase 2 consisted of a qualitative exploratory study in which a panel of 15 experts analyzed the results, using focus group techniques, integrating both phases through the elaboration of metainferences. Phase 3 consisted of a qualitative descriptive study where, through nominal group techniques, agreed proposals for strategies to prevent HAIs were prepared. RESULTS: The panel of experts defined a total of 51 proposals for new strategies: 15 in hand hygiene, 13 in surface cleaning, 13 in the use of devices, and 10 in HAI prevention training. Of all of them, 13 were agreed upon as preferable (medium-high viability and high impact) and 7 as recommendable (low viability and high impact). CONCLUSIONS: In the prevention of HAIs, experts recommend applying different strategies simultaneously, which include innovative, technological and humanization aspects, both in data collection, intervention and training, prioritizing those with the greatest impact. and feasibility.

Contribution of Nischarin/IRAS in CNS development, injury and diseases.

BACKGROUND: Murine Nischarin and its human homolog IRAS are scaffold proteins highly expressed in the central nervous system (CNS). Nischarin was initially discovered as a tumor suppressor protein, and recent studies have also explored its potential value in the CNS. Research on IRAS has largely focused on its effect on opioid dependence. Although the role of Nischarin/IRAS in the physiological function and pathological process of the CNS has gradually attracted attention and the related research results are expected to be applied in clinical practice, there is no systematic review of the role and mechanisms of Nischarin/IRAS in the CNS so far. AIM OF REVIEW: This review will systematically analyze the role and mechanism of Nischarin/IRAS in the CNS, and provide necessary references and possible targets for the treatment of neurological diseases, thereby broadening the direction of Nischarin/IRAS research and facilitating clinical translation. KEY SCIENTIFIC CONCEPTS OF REVIEW: The pathophysiological processes affected by dysregulation of Nischarin/IRAS expression in the CNS are mainly introduced, including spinal cord injury (SCI), opioid dependence, anxiety, depression, and autism. The molecular mechanisms such as factors regulating Nischarin/IRAS expression and signal transduction pathways regulated by Nischarin/IRAS are systematically summarized. Finally, the clinical application of Nischarin/IRAS has been prospected.

Drug therapy and medication adherence in type 2 diabetes in a care facility: A cross sectional survey.

Background: Adherence to medications improves glycaemic control and reduces diabetes-related morbidity and mortality. Objectives: The study assessed drug therapy for type 2 diabetes, glycaemic control and association of medication adherence with socio-demographic and clinical data, among adult diabetic patients attending a healthcare facility. Methods: Cross-sectional survey and hospital records were used to obtain data. The study included 200 adults with type 2 diabetes mellitus in a Nigerian healthcare facility. Data on patients clinical characteristics, diabetes drug therapy and medication adherence were collected, entered and anlaysed using SPSS version 24 (P < 0.05). Primary outcome measure was medication adherence among the patients, while secondary outcome measures was glycaemic control. Results: A total of 200 (100%) respondents participated in the study and the majority 141(70.5%) were over 60 years old. Oral medications were mostly used 187(93.5%), particularly, metformin 199(99.5%) and pioglitazone 100(50.0%), while dipeptidyl peptidase-4 inhibitors were not used at all. Patients mostly had poor glycaemic control 159 (79.5%) and majority 152(76.0%) did not practice self-blood glucose monitoring. Moderate medication adherence was predominant in the population. Class of medicine and socio-demographics were not significantly associated with medication adherence (P > 0.05), unlike results of blood glucose self-tests (p = 0.001). Conclusion: Oral antidiabetics, particularly metformin and pioglitazone were mostly used. Poor glycaemic control and moderate adherence were found in the patients, and medication adherence was associated with self-glucose monitoring. This emphasises the need for regular diabetes education on medication adherence.

IRAS/Nischarin modulates morphine reward by glutamate receptor activation in the nucleus accumbens of mouse brain.

The I1 imidazoline receptor and its candidate protein imidazoline receptor antisera-selected (IRAS)/Nischarin are linked to µ opioid receptor (MOR) functions associated with MOR trafficking. We previously demonstrated that IRAS may play an important role in the development of morphine tolerance and physical dependence in vivo. However, the effects of IRAS on morphine psychological dependence are not fully understood. To extend these studies, we investigated the impact of IRAS on morphine dependence in conditioned place preference (CPP) experiments and explored the underlying mechanisms. Knockout of IRAS enhanced the acquisition and reinstatement of morphine-induced CPP. Conditional-knockout of IRAS in the nucleus accumbens (NAc) reproduced higher CPP, and overexpression of IRAS in the NAc rescued the increased morphine-induced CPP in IRAS-/- mice. IRAS-/- mice showed dramatic cAMP-dependent protein kinase (PKA) activation, upregulation of the phosphorylation of the AMPA receptor GluR1-S845 and NMDA receptor NR1-S897 in the NAc after CPP experiment. Moreover, knockout of IRAS induced an increase in spontaneous excitatory postsynaptic current (sEPSC) frequency and a decrease in the AMPA/NMDA ratio in the NAc after chronic morphine treatment. The selective AMPA receptor antagonist NBQX could inhibit morphine CPP in WT mice, while its effect was significantly reduced in IRAS-/- mice. Together, our results demonstrate that IRAS contributes to the regulation of morphine dependence and that the alteration of glutamatergic transmission in the NAc may participate in the effect of IRAS.

The prehospital care experiences and perceptions of ambulance staff and Eastern European patients: An interview study in Lincolnshire, UK.

Background: EU enlargement after 2004 was a major factor in increasing Eastern European migration to the UK. This population requires access to high quality public services generally, and ambulance services more specifically. To understand how Eastern European migrants use ambulance care, this study explored the perceptions and experiences of ambulance staff and the Eastern European patients themselves. Methods: We undertook qualitative semi-structured interviews across Lincolnshire. Purposive and maximum variation sampling ensured that participants were knowledgeable about Eastern European patients' use of ambulance care and were demographically diverse. Data were analysed using framework analysis. Results: There were interviews with 15 ambulance staff and 12 Eastern European patients. A staff interviewee problematised "Health Tourism", which suggests that migrants deliberately exploit state-funded healthcare. However, most disagreed. Patient interviewees often undertook medical travel to access healthcare in response to perceived healthcare problems in the UK. Medical travel increased the likelihood of ambulance staff encountering foreign medication. Variable quality of, and access to, professional interpreters prompted patients to rely instead on informal interpreters. Patients did not register with GPs perhaps due to limited understanding of how the NHS worked. This led to inappropriate use of ambulance services. Recommendations for service delivery improvements included: Eastern European language information on how and when to use ambulance care; improving GP registration; and greater engagement between the ambulance service and Eastern European communities. Conclusions: Frequent medical travel can limit how Eastern Europeans acculturate to the NHS and anchor roots in the UK. Acculturation is about how migrant cultures adjust to the host country. This is not assimilation, where they dilute their cultural identity. Language and communication barriers, as well as inadequate availability and quality of interpreting services, can impede patient-staff dialogue in time-critical emergencies.

Imine resveratrol analogs (IRAs): The strong antioxidant that can protect lymphocytes from oxidative damage.

Imine resveratrol analogs (IRAs) are promising new agents that can have higher positive effects and, simultaneously, lower negative properties than resveratrol. In this study, three imine hydroxy derivatives (2-((4-hydroxyphenylimino) methyl) phenol [IRA1], 3-((4-hydroxyphenylimino) methyl) phenol [IRA2], and 4-((4-hydroxyphenylimino) methyl) phenol [IRA3]) were prepared and tested in several biological assays. They performed superior to resveratrol in several antioxidant and biological assays, showing high antioxidant capacity and low genotoxicity. Ferric reducing antioxidant power assay (FRAP) and hydroxyl radicals scavenging assay revealed good Fe3+ to Fe2+ reduction and strong inhibition of hydroxyl radical formation, respectively. High dosage (1 mmol/dm3 ) of IRA2 and IRA3 did not cause genotoxicity in human lymphocytes. Moreover, lymphocytes pretreated with all three IRAs accumulated only very few DNA breaks induced by H2 O2 than lymphocytes pretreated with resveratrol. Additionally, the number of detected DNA breaks appearing after removal of damaged DNA bases, 8-oxo-7,8-dihydroguanine (8-oxoG), did not dramatically increase in lymphocytes treated with IRA2. Thus, we concluded that IRAs, especially IRA2, are strong antioxidants with the ability to protect lymphocytes from oxidative damage.

Direct Observation of Plasma-Stimulated Activation of Surface Species Using Multimodal In Situ/Operando Spectroscopy Combining Polarization-Modulation Infrared Reflection-Absorption Spectroscopy, Optical Emission Spectroscopy, and Mass Spectrometry.

Nonthermal plasmas (NTPs) produce reactive chemical environments, including electrons, ions, radicals, and vibrationally excited molecules, that can drive chemistry at temperatures at which such species are thermally inaccessible. There has been growing interest in the integration of conventional catalysis with reactive NTPs to promote novel chemical transformations. Unveiling the full potential of plasma-catalytic processes requires a comprehensive understanding of plasma-catalytic synergies, including characterization of plasma-catalytic surface interactions. In this work, we report on a newly designed multimodal spectroscopic instrument combining polarization-modulation infrared reflection-absorption spectroscopy (PM-IRAS), mass spectrometry, and optical emission spectroscopy (OES) for the investigation of plasma-surface interactions such as those found in plasma catalysis. In particular, this tool has been utilized to correlate plasma-phase chemistry with both surface chemistry and gas-phase products in situ (1) during the deposition of carbonaceous surface species via NTP-promoted nonoxidative coupling of methane and (2) during subsequent activation of surface deposits with an atmospheric pressure and temperature argon plasma jet on both nickel (Ni) and silicon dioxide (SiO2) surfaces. For the first time, the activation of carbonaceous surface species by a NTP on Ni and SiO2 surfaces to form hydrogen gas and C2 hydrocarbons was directly observed, where both PM-IRAS and OES measurements suggest that they may form through different pathways. This unique tool for studying plasma-surface interactions could enable more rational design of plasma-stimulated catalytic processes.

Highly Dispersed Mo Sites on Pd Nanosheets Enable Selective Ethanol-to-Acetate Conversion.

The fermentation of biomass allows for the generation of major renewable ethanol biofuel that has high energy density favorable for direct alcohol fuel cells in alkaline media. However, selective conversion of ethanol to either CO2 or acetate remains a great challenge. Especially, the ethanol-to-acetate route usually demonstrates decentoxidation current density relative to the ethanol-to-CO2 route that contains strongly adsorbed poisons. This makes the total oxidation of ethanol to CO2 unnecessary. Here, we present a highly active ethanol oxidation electrocatalyst that was prepared by in situ decorating highly dispersed Mo sites on Pd nanosheets (MoOx/Pd) via a surfactant-free and facile route. We found that ∼2 atom % of Mo on Pd nanosheets increases the current density to 3.8 A mgPd-1, around 2 times more active relative to the undecorated Pd nanosheets, achieving nearly 100% faradic efficiency for the ethanol-to-acetate conversion in an alkaline electrolyte without the generation of detectable CO2, evidenced by in situ electrochemical infrared spectroscopy, nuclear magnetic resonance, and ion chromatography. The selective and CO2-free conversion offers a promising strategy through alcohol fuel cells for contributing comparable current density to power electrical equipment while for selective oxidation of biofuels to useful acetate intermediate for the chemical industry.

Hydrolysis of Schiff bases with phenyl-ethynyl-phenyl system: The importance for biological and physicochemical studies.

A series of new Schiff bases containing the phenyl-ethynyl-phenyl system was synthesized and their thermal stability, photophysical and electrochemical properties were investigated. Moreover, DFT calculations were performed to obtain the optimized ground-state geometry and distribution of the HOMO and LUMO levels as well as IR spectra of the prepared compounds. It was found that, the photoluminescence of synthesized imines was negligible in all investigated organic solvents except for the PBS/ACN mixture. As was proved in further studies, this phenomenon was related to the partial hydrolysis of imines, which is the source of the fluorogenic aldehyde causing the aggreggacion incrased-emision effect. In further research, due to the susceptibility of the azomethines to partial hydrolysis, the biological activity of 2-{(E)-[4-(phenylethynyl) phenyl]imino}phenol (1b), substrate (2-aminophenol) and Cu(II)-1b complex was analyzed. The biological tests showed, that 1b (as example of imine resveratrol analogue), demonstrated its increased cytostatic activity in prostate cancer cellular system. It was proved that the non-hydrolyzed imine was crucial for the cytotoxic effect. This activity could be ascribed to its Cu(II) complexing capability as showed in our previous research.

The role of IRAS/Nischarin involved in the development of morphine tolerance and physical dependence.

Morphine is a potent opioid analgesic used to alleviate moderate or severe pain, but the development of drug tolerance and dependence limits its use in pain management. Our previous studies showed that the candidate protein for I1 imidazoline receptor, imidazoline receptor antisera-selected (IRAS)/Nischarin, interacts with µ opioid receptor (MOR) and modulates its trafficking. However, there is no report of the effect of IRAS on morphine tolerance and physical dependence. In the present study, we found that IRAS knockout (KO) mice showed exacerbated analgesic tolerance and physical dependence compared to wild-type (WT) mice by chronic morphine treatment. Chronic morphine treatment down-regulated the expression of MOR in spinal cord of IRAS KO mice, while had no significant effect on MOR expression in WT mice. We observed the compensatory increase of cAMP accumulation in spinal cord after morphine tolerance, and this change was more significant in KO mice than WT mice. Furthermore, KO mice showed more elevation in the phosphorylation of AMPA receptor GluR1-S845 than WT mice, while the total expression of GluR1 remained unchanged after morphine dependence. Altogether, these data suggest that IRAS may play an important role in the development of morphine tolerance and physical dependence in vivo through modulating MOR expression, as well as AMPA GluR1-S845 phosphorylation, which might be one of the mechanisms underlying the development of opiate addiction.

Infections related to healthcare in patients hospitalized in a Urology service: resistance patterns and adequacy of empirical antibiotic treatment as a prognostic factor. / Infecciones relacionadas con la asistencia sanitaria en pacientes ingresados en un servicio de Urología: patrones de resistencia y adecuación del tratamiento antibiótico empírico como factor pronóstico.

OBJECTIVES: To evaluate the suitability of empirical antibiotic therapy in HAIs and the antibiotic resistance patterns of the responsible microorganisms, as well as the incidence of mortality and risk factors involved. METHOD: A prospective observational study was carried out on patients of both sexes older than 16years, admitted by any urological process during a period of 4years. The incidence and characteristics of HAIs, as well as the causative organism and its resistance, the initial empirical antibiotic therapy and its modification, if required, and mortality rates are analysed. RESULTS: Out of 6,546 patients, 6.3% suffered HAIs, 70.5% corresponding to urinary tract infection and 22.1% to infection of the surgical wound. E.coli, Enterococcus spp., Klebsiella spp. y P.aeruginosa were the most frequently implicated (25.1%, 17.5%, 13.5% and 12.3%, respectively). E.coli and Klebsiella spp. were producers of extended-spectrum beta-lactamases (ESBL) in 24.7% and 47.8%, respectively. 4.3% of Klebsiella and 33.3% of Pseudomonas were carbapenems-resistant. The overall resistance to quinolones was approximately 50%. The most commonly used antibiotics for empirical therapy were cephalosporins of 3rd and 4th generation (33.6%) and carbapenems (28.2%). An overall rate of adequacy of empirical antibiotic therapy of 82.9% was obtained. The mortality rate in patients with HAIs was 2.2%, compared with 0.3% in patients without infection. In a multivariate analysis, the variables associated with the highest mortality risk were the isolation of ESBL-producing enterobacteria and the inadequate empirical antibiotic treatment. CONCLUSIONS: The selection of empirical antibiotic therapy was quite accurate. An increase in HAIs by multiresistant microorganisms, such as ESBL Enterobacteria or multiresistant P.aeruginosa is being observed. The mortality risk increases with inadequate initial empirical antibiotic therapy or when the responsible microorganism is an ESBL enterobacteria.

Conocimiento, práctica del cuidador y factor pronóstico de infecciones respiratorias agudas en niños / Knowledge, caregiver practice and prognostic factor of acute respiratory infections in children / Conhecimento, prática do cuidador e fator prognóstico de infecções respiratórias agudas em crianças / Connaissance, pratique de l'aidant et facteur pronostique d'infections respiratoires aiguës chez les enfants

Resumen Objetivo: Determinar la relación que existe entre conocimiento, práctica del cuidador de niños menores de 5 años y los factores de mal pronóstico de infecciones respiratorias agudas. Materiales y métodos: Estudio descriptivo, transversal y correlacional, conformado por la consulta externa en el periodo abril-mayo de 2017, seleccionados en un muestreo probabilístico aleatorio sistemático al cual se le aplicó un instrumento que evalúa el conocimiento y la práctica del cuidador en niños menores de 5 años con infecciones respiratorias agudas. Resultados: Cuidadores con conocimiento 56.4% (n=173) y sin conocimiento 43.6% (n=134). Realizaron prácticas correctas 30% (n=92) e incorrectas 70% (n=215). Las prácticas inadecuadas más frecuentes fueron: no realizar medidas para control térmico 62.87% (n=193) y no proporcionar lactancia materna exclusiva 40% (n=123). Los conocimientos deficientes más frecuentes fueron: no reconocer la respiración acelerada 9.2% (n=28) y la fiebre como signos de alarma 25% (n=78). Los niños menores de 5 años con IRAS que presentaron factores de mal pronóstico representaron más de la tercera parte de la población estudiada 47.9% (n=147). Conclusiones: Las madres jóvenes son los principales cuidadores, con escolaridad medio superior y ocupación labores del hogar y que se encuentran dentro de una familia tradicional. En la totalidad de los cuidadores que poseen conocimiento sobre cómo cuidar a los menores con IRAS no realizan prácticas de cuidado correctamente. Los niños en quienes se llevaron a cabo prácticas incorrectas, la mayoría presentó factores de mal pronóstico. No se encontró asociación entre factores de mal pronóstico y nivel de conocimiento y práctica.

Abstract Objective: To determine the relationship between knowledge, caregiver practice of children under 5 years of age and factors of poor prognosis of acute respiratory infections. Materials and methods: Descriptive, cross-sectional and correlational study, formed by the external consultation in April-May 2017 period, selected in a systematic random probabilistic sampling to which an instrument that assesses the knowledge and practice of the caregiver in children was applied. Children under 5 years old with acute respiratory infections. Results: Caregivers with 56.4% (n = 173) knowledge and without 43.6% (n = 134) knowledge. They performed 30% (n = 92) good practices and 70% (n = 215) incorrect. The most frequent inadequate practices were not to perform 62.87% (n = 193) measures for thermal control and not to provide exclusive 40% (n = 123) breastfeeding. The most frequent deficient knowledge were not recognizing 9.2% (n = 28) accelerated breathing and fever as 25% (n = 78) warning signs. Children under 5 years old with IRAS that presented poor prognostic factors accounted for more than a third of the study 47.9% (n = 147) population. Conclusions: Young mothers are the main caregivers, with average schooling and occupation of the home and who are within a traditional family. In all caregivers who have knowledge about how to care for children with IRAS do not perform care practices correctly. Children in whom incorrect practices were carried out, most presented factors of poor prognosis. No association was found between factors of poor prognosis and level of knowledge and practice.

Resumo Objetivo: Determinar a relação entre o conhecimento e a prática de cuidadores de criabas menores de 5 anos e os fatores de mau prognóstico de infecções respiratórias agudas. Materiais e métodos: Estudo descritivo, transversal e correlacional, formado pela consulta externa no período de abril a maio de 2017, selecionado por uma amostragem probabilística aleatória sistemática na que foi aplicado um instrumento que avalia o conhecimento e prática do cuidador em crianças. menores de 5 anos com infecções respiratórias agudas. Resultados: Verificou-se cuidadores com conhecimento 56,4% (n = 173) e sem conhecimento 43,6% (n = 134). Eles realizaram boas práticas 30% (n = 92) e 70% incorretas (n = 215). As práticas inadequadas mais freqüentes foram as que ñao permitiram realizar medidas de controlo térmico 62,87% (n = 193) e as que não permitiram a amamentação exclusiva 40% (n = 123). O conhecimento insuficiente mais freqüente foram: não reconhecer a respiração acelerada 9,2% (n = 28) e febre como sinais de alerta 25% (n = 78). As crianças menores de 5 anos com Insuficiencia Respiratória Aguda que apresentaram fracos fatores prognósticos representaram mais de um terço da população estudada, 47,9% (n = 147). Conclusões: As mães jovens são os principais cuidadores, com escolaridade média e ocupação da casa e que estão dentro de uma familia tradicional. Todos os cuidadores que tem conhecimento sobre como cuidar de crianças com IRAS, náo realizam práticas de cuidados corretamente. A maioria das crianças submetidas a práticas incorretas apresentou fatores de mau prognóstico. Não houve associação entre os fatores de mau prognóstico, o nível de conhecimento e a prática.

Résumé Objectif: Déterminer la relation entre les connaissances et les pratiques des soignants d'enfants de moins de 5 ans, et les facteurs de mauvais pronostic dans les infections respiratoires aigues (IRAS). Matériaux et méthodes: Étude descriptive, transversale et corrélationnelle, avec un échantillon aléatoire systématique provenant de la consultation externe d'avril a mai 2017. Un instrument évaluant les connaissances et les pratiques des aidants d'enfants de moins de 5 ans atteints d'infections respiratoires aigues a été appliqué. Résultats: 56,4% (n = 173) des aidants ont des connaissances et 43,6% (n = 134) n'en ont pas. 30% (n = 92) ont effectué de bonnes pratiques et 70% (n = 215) des pratiques incorrectes. Les pratiques inadéquates les plus fréquentes ont consisté a ne pas effectuer de mesures de contróle thermique (62,87% ; n = 193) et a ne pas fournir d'allaitement maternel exclusif (40% ; n = 123). Le manque de connaissances s'est manifesté le plus fréquemment para l'ignorance des signes avant-coureurs que constituent la respiration accélérée (9,2% ; n = 28) et la fievre (25% ; n = 78). Plus d'un tiers de l'échantillon (47,9% ; n = 147) a présenté des facteurs de mauvais pronostic. Conclusions: Les principales aidantes sont les jeunes meres, avec une scolarité moyenne, dédiées aux taches ménageres et appartenant a une famille traditionnelle. Dans tous les soignants qui ont des connaissances sur la façon de prendre soin des enfants avec IRAS ne pas effectuer correctement les pratiques de soins. Les enfants chez lesquels des pratiques incorrectes ont été pratiquées présentaient pour la plupart des facteurs de mauvais pronostic. Aucune association n'a été trouvée entre les facteurs de mauvais pronostic et le niveau de connaissance et de pratique.

Interaction of Ester-Functionalized Ionic Liquids with Atomically-Defined Cobalt Oxides Surfaces: Adsorption, Reaction and Thermal Stability.

Hybrid materials consisting of ionic liquid (ILs) films on supported oxides hold a great potential for applications in electronic and energy materials. In this work, we have performed surface science model studies scrutinizing the interaction of ester-functionalized ILs with atomically defined Co3 O4 (111) and CoO(100) surfaces. Both supports are prepared under ultra-high vacuum (UHV) conditions in form of thin films on Ir(100) single crystals. Subsequently, thin films of three ILs, 3-butyl-1-methyl imidazolium bis(trifluoromethyl-sulfonyl) imide ([BMIM][NTf2 ]), 3-(4-methoxyl-4-oxobutyl)-1-methylimidazolium bis(trifluoromethyl-sulfonyl) imide ([MBMIM][NTf2 ]), and 3-(4-isopropoxy-4-oxobutyl)-1-methylimidazolium bis(trifluoromethyl-sulfonyl) imide ([IPBMIM][NTf2 ]), were deposited on these surfaces by physical vapor deposition (PVD). Time-resolved and temperature-programmed infrared reflection absorption spectroscopy (TR-IRAS, TP-IRAS) were applied to monitor in situ the adsorption, film growth, and thermally induced desorption. By TP-IRAS, we determined the multilayer desorption temperature of [BMIM][NTf2 ] (360±5 K), [MBMIM][NTf2 ] (380 K) and [IPBMIM][NTf2 ] (380 K). Upon deposition below the multilayer desorption temperature, all three ILs physisorb on both cobalt oxide surfaces. However, strong orientation effects are observed in the first monolayer, where the [NTf2 ]- ion interacts with the surface through the SO2 groups and the CF3 groups point towards the vacuum. For the two functionalized ILs, the [MBMIM]+ and [IPBMIM]+ interact with the surface Co2+ ions of both surfaces via the CO group of their ester function. A very different behavior is found, if the ILs are deposited above the multilayer desorption temperature (400 K). While for [BMIM][NTf2 ] and [MBMIM][NTf2 ] a molecularly adsorbed monolayer film is formed, [IPBMIM][NTf2 ] undergoes a chemical transformation on the CoO(100) surface. Here, the ester group is cleaved and the cation is chemically linked to the surface by formation of a surface carboxylate. The IL-derived species in the monolayer desorb at temperatures around 500 to 550 K.

A Cell-Based High-Throughput Method for Identifying Modulators of Alternative Splicing.

Alternative splicing, a key regulatory process of gene expression, is controlled by trans-acting factors that recognize cis-elements in premature RNA transcripts to affect spliceosome assembly and splice site choices. Extracellular stimuli and signaling cascades can converge on RNA binding splicing regulators to affect alternative splicing. Defects in splicing regulation have been associated with various human diseases, and modification of disease-causing splicing events presents great therapeutic promise. Determining splicing regulators and/or upstream modulators has been difficult with low throughput, low sensitivity, and low specificity. IRAS (identifying regulators of alternative splicing) is a novel cell-based high-throughput screening strategy designed specifically to address these challenges and has achieved high throughput, high sensitivity, and high specificity. Here, we describe the IRAS method in detail with a pair of dual-fluorescence minigene reporters that produces GFP and RFP fluorescent signals to assay the two spliced isoforms exclusively. These two complementary mini-gene reporters alter GFP/RFP output ratios in the opposite direction in response to only a true splicing change. False positives from a signal screen do not stimulate opposite changes in GFP/RFP ratios. The reporter pair in conjunction with robotic liquid handlers and arrayed libraries allows IRAS to screen for both positive and negative splicing regulators with high sensitivity and specificity in a high-throughput manner.

Complex Organic Molecules tracing shocks along the outflow cavity in the high-mass protostar IRAS 20126+4104.

We report on subarcsecond observations of complex organic molecules (COMs) in the high-mass protostar IRAS 20126+4104 with the Plateau de Bure Interferometer in its most extended configurations. In addition to the simple molecules SO, HNCO and H213CO, we detect emission from CH3CN, CH3OH, HCOOH, HCOOCH3, CH3OCH3, CH3CH2CN, CH3COCH3, NH2CN, and (CH2OH)2. SO and HNCO present a X-shaped morphology consistent with tracing the outflow cavity walls. Most of the COMs have their peak emission at the putative position of the protostar, but also show an extension towards the south(east), coinciding with an H2 knot from the jet at about 800-1000 au from the protostar. This is especially clear in the case of H213CO and CH3OCH3. We fitted the spectra at representative positions for the disc and the outflow, and found that the abundances of most COMs are comparable at both positions, suggesting that COMs are enhanced in shocks as a result of the passage of the outflow. By coupling a parametric shock model to a large gas-grain chemical network including COMs, we find that the observed COMs should survive in the gas phase for ∼ 2000 yr, comparable to the shock lifetime estimated from the water masers at the outflow position. Overall, our data indicate that COMs in IRAS 20126+4104 may arise not only from the disc, but also from dense and hot regions associated with the outflow.

Upregulation of IRAS/nischarin (I1-imidazoline receptor), a regulatory protein of µ-opioid receptor trafficking, in postmortem prefrontal cortex of long-term opiate and mixed opiate/cocaine abusers.

Imidazoline receptor antisera-selected (IRAS)/nischarin, a putative I1-imidazoline receptor, has recently been shown to regulate µ-opioid receptor (OR) trafficking and resensitisation. To study a possible involvement of this µ-OR regulator in opiate dependence, the present study assessed by Western blot analysis the contents of IRAS/nischarin and µ-OR in total homogenates and subcellular preparations of postmortem human prefrontal cortex (PFC/BA9) of long-term opiate and mixed opiate/cocaine abusers as well as of matched healthy control subjects. In the PFC/BA9 of long-term opiate/cocaine abusers (all subjects together) IRAS/nischarin content was increased (+67%, p < 0.01, n = 11) when compared with matched controls (n = 10). Similar increases were found for the subgroups of opiate (+72%, n = 6) and mixed opiate/cocaine (+61%, n = 5) abusers. IRAS/nischarin immunocontents were also found increased in subcellular membrane preparations (+61%, p < 0.05, n = 10) of PFC/BA9 from opiate addicts. In the same brain samples, the levels of µ-OR were not different to those in control subjects. Based on the increased contents in brains of opiate abusers and the reported function as µ-OR regulator, IRAS/nischarin could represent a new promising target for treatment of opiate use disorder.

ALMA Compact Array observations of the Fried Egg nebula: Evidence for large-scale asymmetric mass-loss from the yellow hypergiant IRAS 17163-3907.

Yellow hypergiants are rare and represent a fast evolutionary stage of massive evolved stars. That evolutionary phase is characterised by a very intense mass loss, the understanding of which is still very limited. Here we report ALMA Compact Array observations of a 50″-mosaic toward the Fried Egg nebula, around one of the few Galactic yellow hypergiants IRAS 17163-3907. The emission from the 12CO J=2-1 line, H30α recombination line, and continuum is imaged at a resolution of ~8″, revealing the morphology of the molecular environment around the star. The continuum emission is unresolved and peaks at the position of the star. The radio recombination line H30α shows unresolved emission at the star, with an approximately gaussian spectrum centered on a velocity of 21±3 km s-1 with a width of 57±6 km s-1. In contrast, the CO 2-1 emission is complex and decomposes into several components beyond the contamination from interstellar gas in the line of sight. The CO spectrum toward the star is a broad plateau, centered at the systemic velocity of +18 km s-1 and with an expansion velocity of 100±10 km s-1. Assuming isotropic and constant mass-loss, we estimate a mass-loss rate of 8±1.5 ×10-5 M⊙ yr-1. At a radius of 25″ from the star, we detect CO emission associated with the dust ring previously imaged by Herschel. The kinematics of this ring, however, is not consistent with an expanding shell, but show a velocity gradient of vsys ±20 km s-1. In addition, we find a puzzling bright feature radially connecting the star to the CO ring, at a velocity of +40 km s-1 relative to the star. This spur feature may trace a unidirectional ejection event from the star. Our ACA observations reveal the complex morphology around IRAS 17163 and illustrate the breakthroughs that ALMA will bring to the field of massive stellar evolution.

ALMA Observations of the Water Fountain Pre-Planetary Nebula IRAS 16342-3814: High-Velocity Bipolar Jets and an Expanding Torus.

We have mapped 12CO J=3-2 and other molecular lines from the "water-fountain" bipolar pre-planetary nebula (PPN) IRAS 16342-3814 with [Formula: see text] resolution using ALMA. We find (i) two very high-speed knotty, jet-like molecular outflows, (ii) a central high-density (> few × 106 cm-3), expanding torus of diameter 1300 AU, and (iii) the circumstellar envelope of the progenitor AGB, generated by a sudden, very large increase in the mass-loss rate to > 3.5 × 10-4M⊙ yr-1 in the past ~455 yr. Strong continuum emission at 0.89 mm from a central source (690 mJy), if due to thermally-emitting dust, implies a substantial mass (0.017 M⊙) of very large (~mm-sized) grains. The measured expansion ages of the above structural components imply that the torus (age~160 yr) and the younger high-velocity outflow (age~110 yr) were formed soon after the sharp increase in the AGB mass-loss rate. Assuming a binary model for the jets in IRAS 16342, the high momentum rate for the dominant jet-outflow in IRAS 16342 implies a high minimum accretion rate, ruling out standard Bondi-Hoyle-Lyttleton wind accretion and wind Roche lobe overflow (RLOF) models with white-dwarf or main-sequence companions. Most likely, enhanced RLOF from the primary or accretion modes operating within common envelope evolution are needed.

A Molecular-Line Study of the Interstellar Bullet Engine IRAS05506+2414.

We present interferometric and single-dish molecular line observations of the interstellar bullet-outflow source IRAS05506+2414, whose wide-angle bullet spray is similar to the Orion BN/KL explosive outflow and likely arises from an entirely different mechanism than the classical accretion-disk-driven bipolar flows in young stellar objects. The bullet-outflow source is associated with a large pseudo-disk and three molecular outflows - a high-velocity outflow (HVO), a medium-velocity outflow (MVO), and a slow, extended outflow (SEO). The size (mass) of the pseudo-disk is 10,350 AU×6,400 AU (0.64-0.17M⊙); from a model-fit assuming infall and rotation we derive a central stellar mass of 8-19 M⊙. The HVO (MVO) has an angular size ~ 5180 (~ 3330) AU, and a projected outflow velocity of ~ 140 km s-1 (~ 30 km s-1). The SEO size (outflow speed) is ~ 0.9 pc (~ 6 km s-1). The HVO's axis is aligned with (orthogonal to) that of the SEO (pseudo-disk). The velocity structure of the MVO is unresolved. The scalar momenta in the HVO and SEO are very similar, suggesting that the SEO has resulted from the HVO interacting with ambient cloud material. The bullet spray shares a common axis with the pseudo-disk, and has an age comparable to that of MVO (few hundred years), suggesting that these three structures are intimately linked together. We discuss several models for the outflows in IRAS 05506+2414 (including dynamical decay of a stellar cluster, chance encounter of a runaway star with a dense cloud, and close passage of two protostars), and conclude that 2nd-epoch imaging to derive proper motions of the bullets and nearby stars can help to discriminate between them.