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Confocal micro-X-ray fluorescence (micro-XRF) spectroscopy facilitates three-dimensional (3D) elemental imaging of heterogeneous samples in the micrometer range. Laboratory setups using X-ray tube excitation render the method accessible for diverse research fields but interpretation of results and quantification remain challenging. The attenuation of X-rays in composites depends on the photon energy as well as on the composition and density of the material. For confocal micro-XRF, attenuation severely impacts elemental distribution information, as the signal from deeper layers is distorted by superficial layers. Absorption correction and quantification of fluorescence measurements in heterogeneous composite samples have so far not been reported. Here, an absorption correction approach for confocal micro-XRF combining density information from microcomputed tomography (micro-CT) data with laboratory X-ray absorption spectroscopy (XAS) and synchrotron transmission measurements is presented. The energy dependency of the probing volume is considered during the correction. The methodology is demonstrated on a model composite sample consisting of a bovine tooth with a clinically used restoration material.
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The enantioselective hydrogenation of cyclic enamides has been achieved using an earth-abundant cobalt-bisphosphine catalyst. Using CoCl2 /(S,S)-Ph-BPE, several trisubstituted carbocyclic enamides were reduced with high activity and excellent enantioselectivity (up to 99 %) to the corresponding saturated amides. The methodology can be extended to the synthesis of chiral amines by base hydrolysis of the hydrogenation products. Preliminary mechanistic investigations reveal the presence of a high spin cobalt (II) species in the catalytic cycle. We propose that the hydrogenation of the carbon-carbon double bond proceeds via a sigma-bond-metathesis pathway.
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Amidas , Cobalto , Amidas/química , Hidrogenación , Estereoisomerismo , Catálisis , CarbonoRESUMEN
PURPOSE: Curative radiotherapy for cancer may lead to severe late radiation tissue injuries (LRTIs). However, limited knowledge exists about pelvic cancer survivors' LRTI symptoms, distress, and health-related quality of life (HRQOL). We sought to assess the symptom burden, distress, and HRQOL in survivors with established pelvic LRTIs compared to norm populations and to investigate the relation between these factors. METHODS: Cancer survivors referred for treatment of established pelvic LRTIs were recruited nationwide. LTRIs were assessed with the Expanded Prostate Cancer Index Composite (EPIC), psychological distress was assessed with the General Health Questionnaire (GHQ-12), and HRQOL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORCT-QLQ-C30). RESULTS: A total of 107 participants (mean age 64, 53% men) were included. Compared to norms, participants reported more urinary (mean 68.7 vs. 89.5; p = 0.00; d = 1.4) and bowel symptoms (mean 62.5 vs. 92.4; p = 0.00; d = 2.7), increased psychological distress (mean 13.4 vs. 10.3; p = 0.00; d = 0.6), and overall poorer HRQOL (mean 54.9 vs. 71.2; p = 0.00; d = 0.7). Higher symptom burden and higher levels of psychological distress were associated with lower HRQOL (r2 = 46%), but psychological distress did not moderate the influence of symptoms on HRQOL. CONCLUSION: Cancer survivors with established pelvic LRTIs are highly burdened compared to norms. The association of the LRTI-related symptom burden with HRQOL is independent of the level of psychological distress. Both coping and treatment interventions are crucial to promoting long-term health and HRQOL. TRIAL REGISTRATION: NCT03570229.
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Supervivientes de Cáncer , Neoplasias , Distrés Psicológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y Cuestionarios , SobrevivientesRESUMEN
PURPOSE: Late radiation tissue injuries (LRTIs) after treatment for pelvic cancer may impair health related quality of life (HRQoL). Hyperbaric oxygen therapy is an adjuvant therapy for LRTIs, but limited studied. The aim of this study was to explore the development and association between symptoms of LRTI and HRQoL following hyperbaric oxygen treatment. METHODS: A pretest-posttest design was used to evaluate the changes in pelvic LRTIs and HRQoL from baseline (T1), immediately after treatment (T2) and at six-month follow-up (T3). EPIC and EORTC-QLQ-C30 were used to assess LRTIs and HRQoL. Changes were analysed with t-tests, and associations with Pearson's correlation and multiple regression analyses. RESULTS: Ninety-five participants (mean age 65 years, 52.6% men) were included. Scores for urinary and bowel symptoms, overall HRQoL, all function scales and the symptoms scales sleep, diarrhoea, pain and fatigue were significantly improved six months after treatment (P-range = 0.00-0.04). Changes were present already at T2 and maintained or further improved to T3. Only a weak significant correlation between changes in symptoms and overall HRQoL was found (Pearson r-range 0.20-0.27). CONCLUSION: The results indicate improvement of pelvic LRTIs and HRQoL following hyperbaric oxygen therapy, corresponding to minimal or moderate important changes. Cancer survivors with pelvic LRTIs and impaired HRQoL may benefit from undergoing hyperbaric oxygen therapy. Especially the reduced symptom-severity and improved social- and role function can influence daily living positively. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03570229. Released 2. May 2018.
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Supervivientes de Cáncer , Oxigenoterapia Hiperbárica , Neoplasias Pélvicas , Traumatismos por Radiación , Anciano , Femenino , Humanos , Masculino , Neoplasias Pélvicas/radioterapia , Calidad de Vida , Traumatismos por Radiación/etiología , Traumatismos por Radiación/terapiaRESUMEN
A convenient synthesis of enantiopure P-chirogenic diphosphazanes incorporating bulky bisphenol and 1,1'-bi-2-naphthol-derived substituents via the functionalization of a readily accessible enantiopure lithium phosphinoamide with chlorophosphoridites was developed. Since the product requires no subsequent deprotection, the protocol provides an easy, convenient synthesis of P-chirogenic ligands on the gram scale. The ligands were applied in the Rh-catalyzed asymmetric hydrogenation of benchmark substrates furnishing enantiomeric excess values up to 96%.
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BACKGROUND: Late radiation cystitis is an adverse effect of cancer treatment with radiotherapy in the pelvic region. Symptoms of late radiation cystitis can be assessed with the Expanded Prostate Index Composite Score (EPIC). Previous reports indicate that hyperbaric oxygen therapy reduces symptoms from late radiation cystitis, but the evidence is predominantly based on non-randomised and retrospective studies. We aimed to assess whether hyperbaric oxygen therapy would mitigate symptoms of late radiation cystitis. METHODS: We did a randomised, controlled, phase 2-3 trial (RICH-ART [Radiation Induced Cystitis treated with Hyperbaric oxygen-A Randomised controlled Trial]) at five Nordic university hospitals. All patients aged 18-80 years, with pelvic radiotherapy completed at least 6 months previously, a score of less than 80 in the urinary domain of the Expanded Prostate Index Composite Score (EPIC), and referred to participating hyperbaric clinics due to symptoms of late radiation cystitis, were eligible for inclusion. Exclusion criteria were ongoing bleeding requiring blood transfusion exceeding 500 mL in the past 4 weeks, permanent urinary catheter, bladder capacity less than 100 mL, fistula in the urinary bladder, previous treatment with hyperbaric oxygen therapy for late radiation injuries, and contraindications to hyperbaric oxygen therapy. After computer-generated 1:1 randomisation with block sizes of four for each stratification group (sex, time from radiotherapy to inclusion, and previous invasive surgery in the pelvic area), patients received hyperbaric oxygen therapy (30-40 sessions, 100% oxygen, breathed at a pressure of 240-250 kPa, for 80-90 min daily) or standard care with no restrictions for other medications or interventions. No masking was applied. The primary outcome was change in patient-perceived urinary symptoms assessed with EPIC from inclusion to follow-up at visit 4 (6-8 months later), measured as absolute change in EPIC urinary total score. RICH-ART closed enrolment on Dec 31, 2017; the last follow-up data will be compiled in 2023. RICH-ART is registered with ClinicalTrials.gov, number NCT01659723, and with the European Medicines Agency, number EudraCT 2012-001381-15. FINDINGS: Of 223 patients screened between May 9, 2012, and Dec 20, 2017, 87 patients were enrolled and randomly assigned to either hyperbaric oxygen therapy (n=42) or standard care (n=45). After excluding eight patients who withdrew consent directly after randomisation (one in the hyperbaric oxygen therapy group and seven in the standard care group), 79 were included in the intention-to-treat analyses (n=41 in the hyperbaric oxygen therapy group, n=38 in the standard care group). Median time from randomisation to visit 4 was 234 days (IQR 210-262) in the hyperbaric oxygen therapy group and 217 days (195-237) in the standard care group. The difference between change in group mean of EPIC urinary total score at visit 4 was 10·1 points (95% CI 2·2-18·1; p=0·013; 17·8 points [SD 18·4] in the hyperbaric oxygen therapy group vs 7·7 points [15·5] in the standard care group). 17 (41%) of 41 patients in the hyperbaric oxygen therapy group experienced transient grade 1-2 adverse events, related to sight and hearing, during the period of hyperbaric oxygen therapy. INTERPRETATION: Our results suggest that hyperbaric oxygen therapy relieves symptoms of late radiation cystitis. We conclude that hyperbaric oxygen therapy is a safe and well tolerated treatment. FUNDING: The regional research fund of Region Västra Götaland, Sweden, the regional Health Technology Assessment Centre at Sahlgrenska University Hospital, Sweden, and Lions Cancer Research Fund of Western Sweden.
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Braquiterapia/efectos adversos , Cistitis/terapia , Oxigenoterapia Hiperbárica , Neoplasias Pélvicas/radioterapia , Dosis de Radiación , Traumatismos por Radiación/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cistitis/diagnóstico , Cistitis/etiología , Femenino , Humanos , Oxigenoterapia Hiperbárica/efectos adversos , Masculino , Persona de Mediana Edad , Neoplasias Pélvicas/patología , Traumatismos por Radiación/diagnóstico , Traumatismos por Radiación/etiología , Países Escandinavos y Nórdicos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Cerebral gas embolism is a complication of several medical procedures and occurs when gas enters the cerebral circulation. Knowledge about etiology and outcome in affected patients is limited, and prospective trials on management and treatment are hardly feasible. Case reports are therefore an important source of information. METHODS: A systematic literature search was conducted in June 2016 and May 2018, supplemented by a manual search. Titles and abstracts were systematically assessed for eligibility, followed by full-text screening for included papers. Screening and data extraction were performed independently by two researchers. Cases of cerebral gas embolism due to any iatrogenic cause were included. Criteria for exclusion were: animal studies, non-cerebral localization, extravascular gas only, and non-iatrogenic causes. 264 cases reported in 189 papers were included. RESULTS: A broad range of procedures leading to iatrogenic cerebral gas embolism (ICGE) were identified and a comprehensive list is presented in this article. Procedures were mostly reported as conducted correctly, but procedure related error, patient activity, or defective equipment were also reported as causes. Neurological, neuropsychological, and cardiopulmonary symptoms were common. The diagnosis was frequently based on or confirmed by radiology, usually CT. Hyperbaric oxygen therapy was applied in a large number of cases. CONCLUSION: The reported causes, symptoms and signs, and outcomes of ICGE vary significantly, and awareness of the condition in the medical community is essential. A standardized method of reporting could facilitate higher quality research in the field.
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Embolia Aérea/terapia , Enfermedad Iatrogénica , Embolia Aérea/epidemiología , Embolia Aérea/etiología , Humanos , Periodo Perioperatorio , Resultado del TratamientoRESUMEN
OBJECTIVES: Olfactory dysfunction has been related to cognitive deficits in Parkinson's disease (PD), but evidence is conflicting and little is known about the relationship between these symptoms in early PD. Our objective was to study the association between smell deficits measured with a simple odor identification test at diagnosis of PD and the subsequent risk of cognitive decline. MATERIALS & METHODS: One hundred and ninety two PD patients from a population-based study were examined at time of diagnosis, before initiation of dopaminergic treatment, with follow-up of 177 patients after 3 years, 162 patients after 5 years and 146 patients after 7 years. Cognitive function was assessed repeatedly with tests of global cognition, verbal memory, visuospatial abilities, processing speed, and executive function. Olfactory function was tested with a simple odor identification test at baseline. Associations between outcome measures and hyposmia were assessed by linear mixed effects models. RESULTS: After 7 years, there were significant differences in global cognition (B: 1.96 (95% CI: 0.68, 3.24), P = 0.0031), verbal memory including immediate recall (B: 5.36 (95% CI: 2.04, 8.67), P = 0.0018) and delayed recall (B: 1.55 (95% CI: 0.51, 2.59), P = 0.0041) and word reading speed (B: 6.90 (95% CI: 2.17, 11.63), P = 0.0048) between hyposmic and normosmic PD patients. CONCLUSIONS: The decline of cognitive function in early PD is more rapid in patients with hyposmia at diagnosis, compared to normosmic ones. A simple smell test may contribute to identify patients at risk of accelerated decline in global cognition, verbal memory, and processing speed within the first 7 years from diagnosis.
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Disfunción Cognitiva/etiología , Trastornos del Olfato/etiología , Enfermedad de Parkinson/complicaciones , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , OlfatoRESUMEN
To date, a plethora of λ3 -P nitrogen-containing compounds is known. A large number of them are used as ligands in coordination chemistry and homogeneous catalysis. PN-containing compounds tend to build up cyclic moieties, which have received less attention in regard to their application as ligands in transition metal chemistry. Hence, different dehalogenation reactions of N,N-bis{chloro(aryl)-phosphino}-amines have been developed to synthesize different P-N-P containing cyclic compounds. Their coordination behavior to groupâ VI transition metal carbonyls was explored.
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Inhalation uptake of carbon black nanoparticles (CBNP) bears the risk of morphological and functional lung impairment attributed to the highly reactive particle surface area. Chemical particle surface modifications might affect particle-cell interactions; however, thus far these alterations have not been determined. This is the first in vivo study comparing particle-induced acute lung injury using Printex(®)90 (Pr90, 7 µg), Printex®90 covered by benzo[a]pyrene or 9-nitroanthracene (BaP-Pr90, NA-Pr90, 7 µg, 15% BaP or NA by weight), and acetylene carbon black (CB) with polycyclic aromatic hydrocarbons (PAH-AB, 7 µg, 20% PAH by weight). All particles were suspended in distilled water with bovine serum albumin (BSA). In addition, the influence of suspension media was tested using Printex®90 suspended without BSA (Pr90(-BSA), 7 µg). Quartz (DQ12, 7 µg), 70 µl saline (NaCl), and distilled water with or without BSA (H2O(+/-BSA)) were used as reference and controls. It was postulated that CBNP surface modifications trigger pulmonary responses. After oropharyngeal particle aspiration, lung functions were measured 2 d postexposure, followed by lung preparation for histological or bronchoalveolar lavage fluid (BALF) examinations and type II pneumocyte isolation on d 3. Head-out body plethysmography revealed reduced flow rates induced by PAH-AB. Examinations of BALF demonstrated reduced influx of macrophages after exposure to Pr90(-BSA) and decreased lymphocyte levels after Pr90(+BSA) or BaP-Pr90 treatment. Further, CBNP induced changes in mRNA expressions (surfactant proteins) in type II pneumocytes. These findings indicate that CBNP surface area and media modulate interactions between NP and lung cells in short-term experiments.
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Lesión Pulmonar Aguda/fisiopatología , Células Epiteliales Alveolares/efectos de los fármacos , Nanopartículas/toxicidad , Hollín/toxicidad , Acetileno/toxicidad , Lesión Pulmonar Aguda/inducido químicamente , Células Epiteliales Alveolares/fisiología , Animales , Antracenos/toxicidad , Benzo(a)pireno/toxicidad , Femenino , Homeostasis , Ratones , Ratones Endogámicos BALB C , Nanopartículas/química , Hidrocarburos Policíclicos Aromáticos/toxicidad , Hollín/química , Organismos Libres de Patógenos EspecíficosRESUMEN
BACKGROUND: Despite the unprecedented and increasing amount of data, relatively little progress has been made in molecular characterization of mechanisms underlying Parkinson's disease. In the area of Parkinson's research, there is a pressing need to integrate various pieces of information into a meaningful context of presumed disease mechanism(s). Disease ontologies provide a novel means for organizing, integrating, and standardizing the knowledge domains specific to disease in a compact, formalized and computer-readable form and serve as a reference for knowledge exchange or systems modeling of disease mechanism. METHODS: The Parkinson's disease ontology was built according to the life cycle of ontology building. Structural, functional, and expert evaluation of the ontology was performed to ensure the quality and usability of the ontology. A novelty metric has been introduced to measure the gain of new knowledge using the ontology. Finally, a cause-and-effect model was built around PINK1 and two gene expression studies from the Gene Expression Omnibus database were re-annotated to demonstrate the usability of the ontology. RESULTS: The Parkinson's disease ontology with a subclass-based taxonomic hierarchy covers the broad spectrum of major biomedical concepts from molecular to clinical features of the disease, and also reflects different views on disease features held by molecular biologists, clinicians and drug developers. The current version of the ontology contains 632 concepts, which are organized under nine views. The structural evaluation showed the balanced dispersion of concept classes throughout the ontology. The functional evaluation demonstrated that the ontology-driven literature search could gain novel knowledge not present in the reference Parkinson's knowledge map. The ontology was able to answer specific questions related to Parkinson's when evaluated by experts. Finally, the added value of the Parkinson's disease ontology is demonstrated by ontology-driven modeling of PINK1 and re-annotation of gene expression datasets relevant to Parkinson's disease. CONCLUSIONS: Parkinson's disease ontology delivers the knowledge domain of Parkinson's disease in a compact, computer-readable form, which can be further edited and enriched by the scientific community and also to be used to construct, represent and automatically extend Parkinson's-related computable models. A practical version of the Parkinson's disease ontology for browsing and editing can be publicly accessed at http://bioportal.bioontology.org/ontologies/PDON .
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Ontología de Genes , Conocimiento , Enfermedad de Parkinson/genética , Programas Informáticos , Animales , Bases de Datos Genéticas , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Anotación de Secuencia Molecular , Enfermedad de Parkinson/etiologíaAsunto(s)
Embolia Aérea , Oxigenoterapia Hiperbárica , Embolia Intracraneal , Humanos , Enfermedad IatrogénicaRESUMEN
Inhalation of nitrogen and reactive oxygen species (ROS) is known to induce lung inflammation, which is prevented by enzymatic and nonenzymatic antioxidant systems. These agents form nitrated allergens that were shown to enhance allergenicity. The aim of this study was to examine the influence of nitrated proteins on inflammation and antioxidant status of the lung. Ovalbumin (OVA) in nitrated form (nOVA) was intraperitoneally (ip) injected in mice for sensitization and in nitrated or unmodified form for challenge to induce allergic bronchial inflammation. To study the allergen potential of unrelated protein and verify cross-reactivity, nitrated and unmodified keyhole limpet hemocyanin (nKLH, KLH) was used for challenge. Challenge with OVA or nOVA reduced lung function and increased eosinophilia and protein content in bronchoalveolar lavage fluid (BALF). Challenge with nitrated or native OVA or KLH elevated glutathione (GSH) ratio in type II pneumocytes. Reduced mRNA expression of glutathione peroxidase (GPX) 3, glutathione reductase (GR), superoxide dismutase (SOD) 2, and catalase (CAT) was most prominent after challenge with nitrated OVA and nitrated KLH, respectively. Challenge with nOVA enhanced SOD1 mRNA reduction. Immunostaining of GPX 3 and SOD2 increased after challenge with OVA or nOVA, while reactivity of GR and reactivity of SOD2 were reduced after challenge with KLH or nKLH. SOD1 immunostaining was diminished after challenge with nonnitrated OVA or KLH. CAT immunoreaction was similar in all groups. Nitrated proteins without allergenic potential triggered mRNA reduction of antioxidants in type II cells after sensitization with a nitrated allergen but did not induce bronchial inflammation.
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Alérgenos/inmunología , Células Epiteliales Alveolares/inmunología , Antioxidantes/metabolismo , Neumonía/inmunología , Alcohol Deshidrogenasa , Células Epiteliales Alveolares/metabolismo , Animales , Líquido del Lavado Bronquioalveolar , Catalasa/metabolismo , Reacciones Cruzadas , Eosinofilia/inmunología , Femenino , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Hemocianinas/administración & dosificación , Hemocianinas/química , Ratones , Ratones Endogámicos BALB C , Nitrógeno/química , Ovalbúmina/administración & dosificación , Ovalbúmina/química , Neumonía/inducido químicamente , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/administración & dosificación , Especies Reactivas de Oxígeno/efectos adversos , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: Biomedical ontologies offer the capability to structure and represent domain-specific knowledge semantically. Disease-specific ontologies can facilitate knowledge exchange across multiple disciplines, and ontology-driven mining approaches can generate great value for modeling disease mechanisms. However, in the case of neurodegenerative diseases such as Alzheimer's disease, there is a lack of formal representation of the relevant knowledge domain. METHODS: Alzheimer's disease ontology (ADO) is constructed in accordance to the ontology building life cycle. The Protégé OWL editor was used as a tool for building ADO in Ontology Web Language format. RESULTS: ADO was developed with the purpose of containing information relevant to four main biological views-preclinical, clinical, etiological, and molecular/cellular mechanisms-and was enriched by adding synonyms and references. Validation of the lexicalized ontology by means of named entity recognition-based methods showed a satisfactory performance (F score = 72%). In addition to structural and functional evaluation, a clinical expert in the field performed a manual evaluation and curation of ADO. Through integration of ADO into an information retrieval environment, we show that the ontology supports semantic search in scientific text. The usefulness of ADO is authenticated by dedicated use case scenarios. CONCLUSIONS: Development of ADO as an open ADO is a first attempt to organize information related to Alzheimer's disease in a formalized, structured manner. We demonstrate that ADO is able to capture both established and scattered knowledge existing in scientific text.
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Enfermedad de Alzheimer , Almacenamiento y Recuperación de la Información , Modelos Biológicos , Biología Computacional , HumanosRESUMEN
The role of reactive oxygen and nitrogen species in local and systemic defense reactions is well documented. NPR1 and TGA1 are key redox-controlled regulators of systemic acquired resistance in plants. NPR1 monomers interact with the reduced form of TGA1, which targets the activation sequence-1 (as-1) element of the promoter region of defense proteins. Here, we report the effect of the physiological nitric oxide donor S-nitrosoglutathione on the NPR1/TGA1 regulation system in Arabidopsis thaliana. Using the biotin switch method, we demonstrate that both NPR1 and TGA1 are S-nitrosylated after treatment with S-nitrosoglutathione. Mass spectrometry analyses revealed that the Cys residues 260 and 266 of TGA1 are S-nitrosylated and S-glutathionylated even at GSNO concentrations in the low micromolar range. Furthermore, we showed that S-nitrosoglutathione protects TGA1 from oxygen-mediated modifications and enhances the DNA binding activity of TGA1 to the as-1 element in the presence of NPR1. In addition, we observed that the translocation of NPR1 into the nucleus is promoted by nitric oxide. Taken together, our results suggest that nitric oxide is a redox regulator of the NPR1/TGA1 system and that they underline the importance of nitric oxide in the plant defense response.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Unión al ADN/metabolismo , Óxido Nítrico/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Unión al ADN/genética , Regulación de la Expresión Génica de las Plantas , Mutagénesis Sitio-Dirigida , Oxidación-Reducción , ARN de Planta/genética , S-Nitrosoglutatión/farmacologíaRESUMEN
Carbon black nanoparticle (CBNP) applications in high doses have been shown to be harmful to the lung. It is postulated that even small, environmentally relevant concentrations induce changes on lung homeostasis. The present study determined the impact of low-dose single and multiple CBNP (Printex 90) applications on mouse alveolar cell metabolism, especially inflammatory and oxidative stress parameters. Nanoparticles were administered to mice by a single or 8 oropharyngeal aspirations at wk 1, 2, 3, 5, 7, 9, 11, and 12 using 7 µg Printex 90, 7 µg DQ12 quartz (positive control), with water vehicle and saline as negative controls. After 2 d or 3 mo lung function was analyzed. Further lung histology, bronchoalveolar lavage fluid (BALF) parameters, and mRNA expression of cytokines and antioxidants enzymes in type II pneumocytes were measured on d 3 or after 3 mo. Single low-dose Printex 90 application induced no marked alterations in lung functions or BALF phospholipid levels but significant decrease in superoxide dismutase 2 and numerically elevated glutathione peroxidase 3 mRNA expression levels in type II pneumocytes. Multiple CBNP applications produced reduced lung function, collagen accumulation, elevated phospholipid levels in BALF, and a massive infiltration of macrophages. Type II pneumocyte mRNA expression of antioxidative enzymes remained unchanged throughout the subchronic experiment, but showed a significant decrease in interleukin (IL)-6Rα mRNA expression. This study demonstrates that an environmentally relevant CBNP concentration induced an acute inflammatory response, an effect that is exacerbated throughout the subchronic duration.
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Exposición por Inhalación , Pulmón/efectos de los fármacos , Nanopartículas/toxicidad , Alveolos Pulmonares/efectos de los fármacos , Hollín/toxicidad , Células Epiteliales Alveolares/citología , Células Epiteliales Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/enzimología , Células Epiteliales Alveolares/metabolismo , Animales , Antioxidantes/metabolismo , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Citocinas/genética , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Pulmón/inmunología , Pulmón/fisiopatología , Ratones , Ratones Endogámicos BALB C , Pletismografía Total , Reacción en Cadena de la Polimerasa , Alveolos Pulmonares/inmunología , Alveolos Pulmonares/fisiopatología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Organismos Libres de Patógenos Específicos , Factores de TiempoRESUMEN
BACKGROUND: Previous cross-sectional findings from the European Nurses Early Exit Study (NEXT) show that nurses who were dissatisfied with their work schedule tended to consider leaving the nursing profession. Mediating factors in this decision process may be caused by self-perceived poor work ability and/or health. The aim of this paper is to investigate changes in work ability and general health among nurses in relation to requested, forced and denied change of shift schedule. METHODS: Longitudinal data from the NEXT Study was used. In total 11,102 nurses from Belgium, Germany, Finland, the Netherlands, Poland, Slovakia, France and Italy completed both the 'basic questionnaire' (t1) and the '12 month follow-up questionnaire' (t2). To examine the time-effect (repeated measures) and the group-effect of five defined groups of nurses on the Work Ability Index (WAI) and general health (SF36), an adjusted 2-way analysis of covariance (ANCOVA) was performed. RESULTS: The nurses who wanted to, but could not change their shifts during the 12 month follow-up had the lowest initial and follow-up scores for WAI (t1: 37.6, t2: 36.6, p <0.001), lowest general health (t1: 63.9, t2: 59.2, p <0.001) and showed the highest decrease in both outcomes. Shift pattern change in line with the nurses' wishes was associated with improved work ability and to a lesser comparatively low extent with increased decline in health scores. A forced change of shift against the nurses' will was significantly associated with a deteriorating work ability and health. CONCLUSIONS: The findings would suggest that nurses' desire to change their shift patterns may be an indicator for perceived low work ability and/or low health. The results also indicate that fulfilling nurses' wishes with respect to their shift work pattern may improve their personal resources such as work ability and - to somewhat lesser extent - health. Disregarding nurses' preferences, however, bears the risk for further resource deterioration. The findings imply that shift schedule organization may constitute a valuable preventive tool to promote nurses' work ability and - to lesser extent - their perceived health, not least in aging nursing work forces.
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Enfermeras y Enfermeros/estadística & datos numéricos , Admisión y Programación de Personal/estadística & datos numéricos , Tolerancia al Trabajo Programado , Adulto , Europa (Continente)/epidemiología , Femenino , Estado de Salud , Humanos , Satisfacción en el Trabajo , Masculino , Enfermeras y Enfermeros/psicología , Encuestas y Cuestionarios , Tolerancia al Trabajo Programado/psicologíaRESUMEN
BACKGROUND: Aggressive behavior and violence in patients, residents or clients are growing challenges in nursing. Aggressive behavior can have both, physical and psychological consequences for nurses and can lead to a reduced performance at work, demotivation, sickness absence and the premature exit from the nursing profession. To develop purposive strategies and to deal with aggressive behavior and health promotion programs, it is crucial to know more about the prevalence of aggressive behavior from patients and the effect on the work ability of nurses in different types of institutions. METHOD: Data of 1735 German nurses was derived from the European NEXT-Study. Description and analysis of variance for each working area (hospital ward, Intensive Care Unit, psychiatric ward, nursing home and home care) were conducted. The work ability was measured with the Work Ability Index (WAI). The aggressive behavior was measured by one item developed by the NEXT Study Group. Linear regression models were applied to analyze the effect of aggressive behavior on the work ability of nurses in a comparison of the five different working areas. RESULTS: A total of 84.9 percent of the nurses were "sometimes" or "often/always" confronted with aggressive behavior from patients. In the comparison of the five working areas, nurses were exposed to different levels of aggressive behavior, while differences in the work ability of nurses were also observed. It was found that aggressive behavior from patients was associated with reduced work ability in nurses working in hospital wards, nursing homes and home care, but not nurses working in ICUs and psychiatric wards. CONCLUSIONS: The findings indicate that many nurses in Germany are exposed to aggressive behavior from patients, which has negative effect on the nurses' work ability. However, it is assumed that strategies to deal with aggressive behavior could play a buffer role between aggressive behavior and work ability of nurses, highlighting one possibility of intervention in future.