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Interlaboratory evaluations of Mucorales qPCR assays were developed to assess the reproducibility and performance of methods currently used. The participants comprised 12 laboratories from French university hospitals (nine of them participating in the Modimucor study) and 11 laboratories participating in the Fungal PCR Initiative. For panel 1, three sera were each spiked with DNA from three different species (Rhizomucor pusillus, Lichtheimia corymbifera, Rhizopus oryzae). For panel 2, six sera with three concentrations of R. pusillus and L. corymbifera (1, 10, and 100 genomes/ml) were prepared. Each panel included a blind negative-control serum. A form was distributed with each panel to collect results and required technical information, including DNA extraction method, sample volume used, DNA elution volume, qPCR method, qPCR template input volume, qPCR total reaction volume, qPCR platform, and qPCR reagents used. For panel 1, assessing 18 different protocols, qualitative results (positive or negative) were correct in 97% of cases (70/72). A very low interlaboratory variability in Cq values (SD = 1.89 cycles) were observed. For panel 2 assessing 26 different protocols, the detection rates were high (77-100%) for 5/6 of spiked serum. There was a significant association between the qPCR platform and performance. However, certain technical steps and optimal combinations of factors may also impact performance. The good reproducibility and performance demonstrated in this study support the use of Mucorales qPCR as part of the diagnostic strategy for mucormycosis.
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Técnicas de Laboratorio Clínico/normas , ADN de Hongos/genética , Técnicas de Diagnóstico Molecular/normas , Mucorales/genética , Mucormicosis/sangre , Mucormicosis/diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Técnicas de Laboratorio Clínico/instrumentación , Técnicas de Laboratorio Clínico/métodos , Francia , Hospitales Universitarios/estadística & datos numéricos , Humanos , Variaciones Dependientes del Observador , Reproducibilidad de los ResultadosRESUMEN
The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.
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Susceptibilidad a Enfermedades , Variación Genética , Inmunidad/genética , Leucemia Mieloide Aguda/etiología , Adulto , Anciano , Alelos , Biomarcadores de Tumor , Susceptibilidad a Enfermedades/inmunología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Inmunomodulación/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Medición de Riesgo , Factores de Riesgo , Esteroides/metabolismoRESUMEN
Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10-7) and primary monocytes (P = 4.31 · 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development.
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Translocador Nuclear del Receptor de Aril Hidrocarburo/genética , Aspergillus/inmunología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Receptor 1 de Quimiocinas CX3C/genética , Predisposición Genética a la Enfermedad , Aspergilosis Pulmonar Invasiva/genética , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Genotipo , Enfermedades Hematológicas/complicaciones , Humanos , Medición de RiesgoRESUMEN
AIM: Patients with inflammatory bowel disease (IBD) are at increased risk of postoperative venous thromboembolism (VTE) following major abdominal surgery. The pathogenesis is multifactorial and not fully understood. A combination of pathophysiology, patient and surgical risk factors increase the risk of postoperative VTE in these patients. Despite being at increased risk, IBD patients are not regularly prescribed extended pharmacological thromboprophylaxis following colorectal surgery. Currently, there is a paucity of evidence-based guidelines. Thus, the aim of this review is to evaluate the role of extended pharmacological thromboprophylaxis in IBD patients undergoing colorectal surgery. METHOD: A search of Ovid Medline, EMBASE and PubMed databases was performed. A qualitative analysis was performed using 10 clinical questions developed by colorectal surgeons and a thrombosis haematologist. The Newcastle-Ottawa Scale was utilized to assess the quality of evidence. RESULTS: A total of 1229 studies were identified, 38 of which met the final inclusion criteria (37 retrospective, one case-control). Rates of postoperative VTE ranged between 0.6% and 8.9%. Patient-specific risk factors for postoperative VTE included ulcerative colitis, increased age and obesity. Surgery-specific risk factors for postoperative VTE included open surgery, emergent surgery and ileostomy creation. Patients with IBD were more frequently at increased risk in the included studies for postoperative VTE than patients with colorectal cancer. The risk of bias assessment demonstrated low risk of bias in patient selection and comparability, with variable risk of bias in reported outcomes. CONCLUSION: There is a lack of evidence regarding the use of extended pharmacological thromboprophylaxis in patients with IBD following colorectal surgery. As these patients are at heightened risk of postoperative VTE, future study and consideration of the use of extended pharmacological thromboprophylaxis is warranted.
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Cirugía Colorrectal , Enfermedades Inflamatorias del Intestino , Tromboembolia Venosa , Anticoagulantes , Humanos , Enfermedades Inflamatorias del Intestino/cirugía , Complicaciones Posoperatorias , Estudios RetrospectivosRESUMEN
Establishing the etiology of invasive fungal infections is important to guide therapeutic options and for epidemiologic purposes. Formalin-fixed, paraffin-embedded (FFPE) tissue specimens from patients with proven invasive fungal infections are valuable to determine the etiology of systemic fungal infections. We compared different polymerase chain reaction (PCR) amplification strategies from FFPE tissue blocks to identify agents of invasive fungal infections. We found that specific PCR assays show superior sensitivity in the identification of DNA of Mucorales and Aspergillus and mixed infections caused by both as compared to broad-range PCR assays. Shorter amplicon lengths and less detection of contaminating fungal DNA are potential factors involved. However, detection of fungal DNA by highly sensitive specific PCR assays in the absence of demonstration of fungal elements in tissue suggests that PCR results should be interpreted in the context of the histopathology and clinical findings.
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Aspergillus/genética , Coinfección/diagnóstico , Mucorales/genética , Micosis/diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Aspergillus/aislamiento & purificación , Coinfección/microbiología , ADN de Hongos/genética , Fijadores , Formaldehído/química , Humanos , Infecciones Fúngicas Invasoras/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Mucorales/aislamiento & purificación , Mucormicosis/diagnóstico , Adhesión en ParafinaRESUMEN
In this study, stearoyl-ACP desaturase (SAD), the enzyme that converts stearic acid into oleic acid, is silenced by artificial microRNA in the green microalga Chlamydomonas reinhardtii. Two different constructs, which target different positions on the mRNA of stearoyl-ACP desaturase, were tested. The mRNA levels for SAD were reduced after the silencing construct was induced. In one of the strains, the reduction in SAD mRNA resulted in a doubling of the stearic acid content in triacylglycerol molecules, which shows that stearic acid production in microalgae is possible.
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Chlamydomonas reinhardtii , Silenciador del Gen , Ácidos Esteáricos , Ácido Graso Desaturasas , Ácido OléicoRESUMEN
BACKGROUND: Frontal aslant tract (FAT) is a white matter bundle connecting the pre-supplementary motor area (pre-SMA) and the supplementary motor area (SMA) with the inferior frontal gyrus (IFG). The purpose of the present study was to evaluate the anatomical variability of FAT. MATERIALS AND METHODS: Total number of fibres and the lateralisation index (LI) were calculated. We attempted to find factors contributing to the diversity of FAT regarding IFG terminations to the pars opercularis (IFG-Op) and to the pars triangularis (IFG-Tr). Magnetic resonance imaging of adult patients with diffusion tensor imaging (DTI) with total number of 98 hemispheres composed a cohort. V-shaped operculum was the most common (60.5%). RESULTS: Total number of FAT fibres had widespread and unimodal distribution (6 to 1765; median: 160). Left lateralisation was noted in 64.3% of cases and was positively correlated with total number of FAT fibres and the bundle projecting to IFG-Op (p < 0.01). LI correlated with total number of FAT fibres (r = 0.43, p < 0.01). FAT projected predominantly to IFG-Op (88.9%; 88 of 99). Only in 3 (3.1%) cases more fibres terminated in IFG-Tr than in IFG-Op. Total number of FAT fibres and number of fibres terminating at IFG-Op did not correlate with the ratio of fibre numbers: FAT/IFG-Op, FAT/IFG-Tr and IFG-Op/IFG-Tr (p > 0.05). The greater total number of fibres to IFG-Tr was, the higher were the ratios of IFG-Tr/ /FAT (r = 0.57, p < 0.01) and IFG-Tr/IFG-Op (r = 0.32, p = 0.04). CONCLUSIONS: Among the IFG, the major termination of FAT is IFG-Op. Whereas the IFG-Tr projection seems to be related to the expansion of the entire FAT bundle regardless of side, domination and handedness. Nevertheless, FAT features a significant anatomical variability which cannot be explained in terms of DTI findings.
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Approximately 40-50% of the population over 80years of age suffers from sarcopenia making this condition a major geriatric clinical disorder and a key challenge to healthy aging. The hallmark symptom of sarcopenia is the loss of muscle mass and strength without the loss of overall body weight. Sarcopenic patients are likely to have worse clinical outcomes and higher mortality compared to healthy individuals. This review will focus on animal models designed to study sarcopenia including hind-limb unloading, de-nervation, and immobilization by using casts or wire strategies, as well as using aged rodents. Currently there are no registered treatments for sarcopenia. Most sarcopenic individuals show signs of physical frailty, which leads to increases the prevalence of balance disorders, falls, fractures and pain. Therefore, is it essential to develop and use relevant animal models to further the research on sarcopenia therapy?
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Modelos Animales de Enfermedad , Músculo Esquelético/fisiopatología , Sarcopenia/fisiopatología , Anciano , Envejecimiento/patología , Envejecimiento/fisiología , Animales , Anciano Frágil , Suspensión Trasera/métodos , Humanos , Músculo Esquelético/patología , Sarcopenia/diagnósticoRESUMEN
The microalgae Tetradesmus obliquus is able to maintain a high photosynthetic efficiency under nitrogen limitation and is considered a promising green microalgae for sustainable production of diverse compounds, including biofuels. Here, we report the first draft whole-genome shotgun sequencing of T. obliquus The final assembly comprises 108,715,903 bp with over 1,368 scaffolds.
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BACKGROUND: Persistent pain is frequent after thoracotomy, with a reported prevalence of up to 60%. It remains unclear why some patients develop pain, whereas others do not. We therefore examined patients with and without pain after thoracotomy to identify pathophysiological contributors to persistent pain. METHODS: Twenty patients with persistent pain, 12 patients without pain and 20 healthy controls underwent detailed functional and structural assessment including psychometric and neuropathic pain questionnaires, bedside examination for pinprick hyperalgesia and brush allodynia, quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain, measurement of capsaicin-evoked flare response, intradermal nerve density as determined by skin biopsies and laser- and heat-evoked potentials. RESULTS: Bedside testing revealed evoked pain in 16 of 20 patients with pain, but only in 2 of 12 patients without pain (p < 0.001). Quantitative sensory testing showed increased mechanical pain sensitivity (p = 0.018) on the operated side in patients with pain, but there were no differences between the two patient groups with regard to intradermal nerve fibre density, area and flux following capsaicin application and laser- and heat-evoked potentials. CONCLUSION: Different and individual pathophysiological mechanisms of pain may obscure the clinical picture and thus preclude identification of a specific pain profile in patients with persistent post-thoracotomy pain. SIGNIFICANCE: Evoked pain is more frequent in patients with pain. Assessment of intradermal nerve density, capsaicin-induced flare response and contact and laser heat-evoked potentials revealed no differences between pain patients and pain-free patients.
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Hiperalgesia/etiología , Dolor Postoperatorio/etiología , Toracotomía/efectos adversos , Adulto , Potenciales Evocados/fisiología , Femenino , Calor , Humanos , Hiperalgesia/fisiopatología , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodos , Dolor Postoperatorio/fisiopatología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Piel/inervaciónRESUMEN
Invasive aspergillosis (IA) is associated with significant morbidity and mortality, and, among other factors, this is due to a delay in diagnosis performed with conventional techniques. A prospective, multicentre study was conducted to evaluate the efficacy of Aspergillus DNA screening in the early diagnosis of IA. Patients undergoing haematopoietic stem cell transplantation or chemotherapy for acute leukaemia were enrolled for biomarker screening. Three centres applied the same protocol for in-house PCR, which was compliant with the European Aspergillus PCR Initiative recommendations, to guarantee the highest diagnostic standards. Two thousand one hundred and twenty-eight sera from 213 patients were investigated and stratified according to the revised European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria for invasive fungal disease. The incidence rates of probable and possible IA were 18% and 38%, respectively. The sensitivity, specificity and positive predictive value (PPV) of PCR were superior in antifungal drug-naive patients, being 71.4%, 92.3%, and 62.5%, respectively. The last of these key performance indicators (PPV) was moderate in patients receiving primary prophylaxis, at 5.4%. Negative predictive values for both strategies applied were 100% with and 98.3% without antifungal mould prophylaxis. PCR has the potential to play a decisive role in the diagnosis and management of Aspergillus infections in centres not applying primary antifungal mould prophylaxis.
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Aspergilosis/diagnóstico , Aspergillus/aislamiento & purificación , ADN de Hongos/análisis , Tamizaje Masivo/métodos , Técnicas de Diagnóstico Molecular/métodos , Reacción en Cadena de la Polimerasa/métodos , Adulto , Anciano , Aspergilosis/epidemiología , Aspergilosis/microbiología , Aspergillus/genética , ADN de Hongos/genética , Diagnóstico Precoz , Femenino , Humanos , Huésped Inmunocomprometido , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Recent studies suggest that immune-modulating single-nucleotide polymorphisms (SNPs) influence the risk of developing cancer-related infections. Here, we evaluated whether 36 SNPs within 14 immune-related genes are associated with the risk of invasive aspergillosis (IA) and whether genotyping of these variants might improve disease risk prediction. We conducted a case-control association study of 781 immunocompromised patients, 149 of whom were diagnosed with IA. Association analysis showed that the IL4Rrs2107356 and IL8rs2227307 SNPs (using dbSNP numbering) were associated with an increased risk of IA (IL4Rrs2107356 odds ratio [OR], 1.92; 95% confidence interval [CI], 1.20 to 3.09; IL8rs2227307 OR, 1.73; 95% CI, 1.06 to 2.81), whereas the IL12Brs3212227 and IFNγrs2069705 variants were significantly associated with a decreased risk of developing the infection (IL12Brs3212227 OR, 0.60; 95% CI, 0.38 to 0.96; IFNγrs2069705 OR, 0.63; 95% CI, 0.41 to 0.97). An allogeneic hematopoietic stem cell transplantation (allo-HSCT)-stratified analysis revealed that the effect observed for the IL4Rrs2107356 and IFNγrs2069705 SNPs was stronger in allo-HSCT (IL4Rrs2107356 OR, 5.63; 95% CI, 1.20 to 3.09; IFNγrs2069705 OR, 0.24; 95% CI, 0.10 to 0.59) than in non-HSCT patients, suggesting that the presence of these SNPs renders patients more vulnerable to infection, especially under severe and prolonged immunosuppressive conditions. Importantly, in vitro studies revealed that carriers of the IFNγrs2069705C allele showed a significantly increased macrophage-mediated neutralization of fungal conidia (P = 0.0003) and, under stimulation conditions, produced higher levels of gamma interferon (IFNγ) mRNA (P = 0.049) and IFNγ and tumor necrosis factor alpha (TNF-α) cytokines (P value for 96 h of treatment with lipopolysaccharide [PLPS-96 h], 0.057; P value for 96 h of treatment with phytohemagglutinin [PPHA-96 h], 0.036; PLPS+PHA-96 h = 0.030; PPHA-72 h = 0.045; PLPS+PHA-72 h = 0.018; PLPS-96 h = 0.058; PLPS+PHA-96 h = 0.0058). Finally, we also observed that the addition of SNPs significantly associated with IA to a model including clinical variables led to a substantial improvement in the discriminatory ability to predict disease (area under the concentration-time curve [AUC] of 0.659 versus AUC of 0.564; P-2 log likehood ratio test = 5.2 · 10(-4) and P50.000 permutation test = 9.34 · 10(-5)). These findings suggest that the IFNγrs2069705 SNP influences the risk of IA and that predictive models built with IFNγ, IL8, IL12p70, and VEGFA variants can used to predict disease risk and to implement risk-adapted prophylaxis or diagnostic strategies.
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Aspergilosis/genética , Aspergilosis/inmunología , Predisposición Genética a la Enfermedad , Interferón gamma/genética , Subunidad p40 de la Interleucina-12/genética , Subunidad alfa del Receptor de Interleucina-4/genética , Interleucina-8/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Alelos , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Huésped Inmunocomprometido/genética , Interferón gamma/inmunología , Subunidad p40 de la Interleucina-12/inmunología , Subunidad alfa del Receptor de Interleucina-4/inmunología , Interleucina-8/inmunología , Masculino , Persona de Mediana EdadRESUMEN
This study investigates the phase shift induced by Laue transmission in a perfect Si crystal blade in unprecedented detail. This `Laue phase' was measured at two wavelengths in the vicinity of the Bragg condition within a neutron interferometer. In particular, the sensitivity of the Laue phase to the alignment of the monochromator and interferometer (rocking angle) and beam divergence has been verified. However, the influence of fundamental quantities, such as the neutron-electron scattering length, on the Laue phase is rather small. The fascinating steep phase slope of 5.5° [(220) Bragg peak] and 11.5° [(440) Bragg peak] per 0.001â arcsec deviation from the Bragg angle has been achieved. The results are analysed using an upgraded simulation tool.
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BACKGROUND: Nasal polyposis frequently occurs within the clinical picture of aspirin-exacerbated respiratory disease (AERD). A derailed arachidonic acid metabolism is regarded to be part of the pathophysiology of AERD, and aspirin desensitization is the only causal therapeutic option, so far. The optimal maintenance dose of aspirin desensitization to prevent nasal polyp recurrence on the one hand and to minimize aspirin-related side-effects, on the other hand, is still a matter of debate. The aim of this trial was to investigate the efficacy and safety of a low-dose aspirin desensitization protocol. METHODS: After sinus surgery, 70 individuals with AERD were randomly allocated to a prospective double-blind placebo-controlled aspirin desensitization protocol with a maintenance dose of 100 mg daily. The primary outcome was polyp relapse after 36 months. Nasal endoscopy status, quality of life, and patients' symptom score as well as aspirin-related side-effects were monitored. RESULTS: Due to the high dropout rate, only 31 individuals were evaluated. After 36 months, nasal polyp relapse was less frequent (P = 0.0785) and the polyposis score was lower (P = 0.0702) in the therapy group. Quality of life obviously improved (P = 0.0324), clinical complaints (P = 0.0083) were significantly reduced, and no severe aspirin-related side-effects were observed. CONCLUSION: Aspirin desensitization with a maintenance dose of 100 mg daily has a positive impact on nasal polyp relapse and seems to be a safe and suitable therapy to improve clinical complaints and the quality of life of individuals with AERD.
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Aspirina/administración & dosificación , Desensibilización Inmunológica , Hipersensibilidad a las Drogas/terapia , Hipersensibilidad Respiratoria/terapia , Adulto , Aspirina/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Recurrencia , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Anesthesiologists have a well-known increased risk of substance abuse including the intravenous administration of opioids and propofol. However, katamnestic reports from the point of view of propofol-addicted anesthesiologists themselves are missing which would aid a better understanding of the dynamics and progress of addiction. This article presents an interview with a formerly addicted female anesthesiologist who after long-term abuse with oral tilidine combined with naloxone switched to intravenous administration of fentanyl and later on propofol. Several life-threatening incidents occurred but after some severe setbacks occupational rehabilitation outside the field of anesthesiology was successful following inpatient treatment. This case shows exemplarily in accordance with the current literature that warning signs in addicted physicians are often ignored by colleagues and supervisors and rehabilitation is possible under professional therapy and continuous surveillance. Additionally, this case emphasizes the necessity of controlling the distribution of propofol to reduce the life-threatening professional risk to anesthesiologists.
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Analgésicos Opioides , Anestésicos Intravenosos , Fentanilo , Trastornos Relacionados con Opioides/terapia , Inhabilitación Médica/psicología , Médicos , Propofol , Trastornos Relacionados con Sustancias/terapia , Adulto , Anestesiología , Femenino , Humanos , Naloxona , Trastornos Relacionados con Opioides/rehabilitación , Desvío de Medicamentos bajo Prescripción , Abuso de Sustancias por Vía Intravenosa , Trastornos Relacionados con Sustancias/rehabilitación , Sobrevivientes , TilidinaRESUMEN
The currently largest perfect-crystal neutron interferometer with six beam splitters and two interference loops offers novel applications in neutron interferometry. The two additional lamellas can be used for quantitative measurements of a phase shift due to crystal diffraction in the vicinity of a Bragg condition. The arising phase, referred to as "Laue phase," reveals an extreme angular sensitivity, which allows the detection of beam deflections of the order of 10(-6) s of arc. Furthermore, a precise measurement of the Laue phase at different reflections might constitute an interesting opportunity for the extraction of fundamental quantities like the neutron-electron scattering length, gravitational short-range interactions in the sub-micron range and the Debye Waller factor. For that purpose several harmonics can be utilized at the interferometer instrument ILL-S18.
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The occurrence of infections due to previously rare opportunistic pathogens is increasing despite the use of novel treatment strategies for immunocompromised patients. Here, we report the case of a patient presenting with fever, muscle pain, and bilateral endophthalmitis after allogeneic hematopoietic stem cell transplantation. Fusarium solani was isolated from peripheral blood samples and identified as the cause of gradual bilateral vision loss, despite appropriate antifungal prophylaxis, and therapy including vitrectomy and intraocular instillation of antifungal agents. The patient became comatose; basal meningitis involving both optic nerves was suspected based on magnetic resonance tomography. The patient died 8 days later due to septic multi-organ failure. Autopsy revealed that both kidneys, but no other organs, were infiltrated by Fusarium. No fungus was found in cerebral tissues or cerebrospinal fluid. Our case demonstrates some of the typical clinical features of systemic fusariosis and its potentially fatal outcome. The clinical observations reported here may help clinicians caring for immunocompromised patients to accelerate diagnosis and initiate treatment early at the onset of this fatal complication, and highlight the urgent need for interdisciplinary management of invasive fusariosis.
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Endoftalmitis/microbiología , Infecciones Fúngicas del Ojo/microbiología , Fusariosis/patología , Fusarium/patogenicidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante Homólogo/efectos adversos , Anciano , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Endoftalmitis/tratamiento farmacológico , Endoftalmitis/patología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/patología , Resultado Fatal , Fusariosis/tratamiento farmacológico , Fusariosis/microbiología , Fusarium/efectos de los fármacos , Fusarium/aislamiento & purificación , Humanos , Huésped Inmunocomprometido , Masculino , Triazoles/uso terapéuticoRESUMEN
BACKGROUND: Real science has the potential to not only amaze, but also transform the way one thinks of the world and oneself. This is because the process of science is little different from the deeply resonant, natural processes of play. Play enables humans (and other mammals) to discover (and create) relationships and patterns. When one adds rules to play, a game is created. THIS IS SCIENCE: the process of playing with rules that enables one to reveal previously unseen patterns of relationships that extend our collective understanding of nature and human nature. When thought of in this way, science education becomes a more enlightened and intuitive process of asking questions and devising games to address those questions. But, because the outcome of all game-playing is unpredictable, supporting this 'messyness', which is the engine of science, is critical to good science education (and indeed creative education generally). Indeed, we have learned that doing 'real' science in public spaces can stimulate tremendous interest in children and adults in understanding the processes by which we make sense of the world. The present study (on the vision of bumble-bees) goes even further, since it was not only performed outside my laboratory (in a Norman church in the southwest of England), but the 'games' were themselves devised in collaboration with 25 8- to 10-year-old children. They asked the questions, hypothesized the answers, designed the games (in other words, the experiments) to test these hypotheses and analysed the data. They also drew the figures (in coloured pencil) and wrote the paper. Their headteacher (Dave Strudwick) and I devised the educational programme (we call 'i,scientist'), and I trained the bees and transcribed the childrens' words into text (which was done with smaller groups of children at the school's local village pub). So what follows is a novel study (scientifically and conceptually) in 'kids speak' without references to past literature, which is a challenge. Although the historical context of any study is of course important, including references in this instance would be disingenuous for two reasons. First, given the way scientific data are naturally reported, the relevant information is simply inaccessible to the literate ability of 8- to 10-year-old children, and second, the true motivation for any scientific study (at least one of integrity) is one's own curiousity, which for the children was not inspired by the scientific literature, but their own observations of the world. This lack of historical, scientific context does not diminish the resulting data, scientific methodology or merit of the discovery for the scientific and 'non-scientific' audience. On the contrary, it reveals science in its truest (most naive) form, and in this way makes explicit the commonality between science, art and indeed all creative activities. PRINCIPAL FINDING: 'We discovered that bumble-bees can use a combination of colour and spatial relationships in deciding which colour of flower to forage from. We also discovered that science is cool and fun because you get to do stuff that no one has ever done before. (Children from Blackawton)'.
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Abejas/fisiología , Visión de Colores , Reconocimiento Visual de Modelos , Animales , Conducta Animal , Conducta EspacialRESUMEN
The phenomenon of a neutron phase shift due to Laue transmission in a perfect crystal blade is discussed. Quantitative measurements of this phase shift are presented in the vicinity of the Bragg condition well in agreement with numerical calculations. The phase shift shows a strong angular sensitivity and might constitute an interesting opportunity for precision measurements of fundamental quantities like the neutron-electron scattering length or gravitational short-range interactions.
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This study adds to the limited research on the potential importance of the quality of the relationship between adult prevention service providers and youth participants in enhancing social skills and strengthening prevention outcomes. Study subjects were drawn from seven prevention programs funded under a Youth Mentoring Initiative by the Center for Substance Abuse Prevention in the Substance Abuse and Mental Health Services Administration. These programs maintain a relationship-based service focus but use a variety of one-on-one, group, volunteer, and paid staff service formats. Study results showed that youth who perceived a higher level of trust, mutuality and empathy in their relationship with providers experienced significantly greater improvements in social skills (i.e., cooperation, self-control, assertiveness, and empathy) than program participants who perceived a lower quality relationship with adult providers. These findings underscore the importance of recruitment, training and supervisory practices that promote staff and volunteer skills in achieving high quality relationships with youth participants regardless of the specific intervention strategy. Editors' Strategic Implications: Practitioners and policymakers should review the authors' findings about the importance of individual adult skills in building protective mentoring relationships. The impact of relationship quality, rather than setting, suggests that the scope of effective prevention practice can be broadened beyond the confines of formal prevention programming to any place in which caring and skilled adults interact with youth.