20 research outputs found

    Pseudouridine at position 55 in tRNA controls the contents of other modified nucleotides for low-temperature adaptation in the extreme-thermophilic eubacterium Thermus thermophilus

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    Pseudouridine at position 55 (Ψ55) in eubacterial tRNA is produced by TruB. To clarify the role of the Ψ55 modification, we constructed a truB gene disruptant (ΔtruB) strain of Thermus thermophilus which is an extreme-thermophilic eubacterium. Unexpectedly, the ΔtruB strain exhibited severe growth retardation at 50°C. We assumed that these phenomena might be caused by lack of RNA chaperone activity of TruB, which was previously hypothetically proposed by others. To confirm this idea, we replaced the truB gene in the genome with mutant genes, which express TruB proteins with very weak or no enzymatic activity. However the growth retardation at 50°C was not rescued by these mutant proteins. Nucleoside analysis revealed that Gm18, m5s2U54 and m1A58 in tRNA from the ΔtruB strain were abnormally increased. An in vitro assay using purified tRNA modification enzymes demonstrated that the Ψ55 modification has a negative effect on Gm18 formation by TrmH. These experimental results show that the Ψ55 modification is required for low-temperature adaptation to control other modified. 35S-Met incorporation analysis showed that the protein synthesis activity of the ΔtruB strain was inferior to that of the wild-type strain and that the cold-shock proteins were absence in the ΔtruB cells at 50°C

    Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation: an individual patient data meta‑analysis

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    Background Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaave’s syndrome (BS). Methods We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (≤ 24 h) and late (> 24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission. Results Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8–5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2–7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2–6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, p < 0.001), compared with late TOD. In BS, no associations between TOD and outcomes were found. When combining IEP and BS, early TOD was associated with a 6% decrease in overall mortality (10% vs. 16%, OR 2.1, 95% CI 1.1–3.9), a 19% decrease in re-interventions (26% vs. 45%, OR 1.9, 95% CI 1.1–3.2) and a 35% decrease in mean length of hospital stay (16 vs. 22 days, p = 0.001), compared with late TOD. Conclusions This individual patient data meta-analysis confirms the general opinion that an early (≤ 24 h) compared to a late diagnosis (> 24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome.publishedVersio

    Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation: an individual patient data meta-anal

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    Background: Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaave’s syndrome (BS). Methods: We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (≤ 24 h) and late (> 24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission. Results: Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8–5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2–7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2–6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, p 24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome

    Predictors for failure of stent treatment for benign esophageal perforations - a single center 10-year experience

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    VARFÖR BLIR PATIENTER FELMEDICINERADE NÄR DE ÄR INLAGDA PÅ SOMATISK SLUTENVÅRD?

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    Felmedicineringar inom somatisk slutenvård är ett allvarligt hot mot patientsäkerheten. Läkemedelsbehandling är en central del av modern sjukvård och ett viktigt ansvarsområde för sjuksköterskan. Syftet med denna litteraturstudie var att undersöka vilka faktorer som påverkar patientsäkerheten vid sjuksköterskans läkemedelshantering inom somatisk slutenvård. Sjuksköterskans arbetsmiljö kan på olika sätt antingen medverka till eller motverka patientsäkerheten vid läkemedelhantering då många faktorer interagerar i denna komplexa miljö och process. Denna litteraturstudie är deskriptiv med en systematisk ansats med avsikt att sammanställa och lokalisera aktuell forskning. Via databassökningar på PubMed och CHINAL har relevanta artiklar identifierats. Resultatet, som baseras på tio vetenskapliga studier visar hur dynamisk och multifaktoriell sjuksköterskans arbetsmiljö är, och hur detta kan påverka patientsäkerheten vid läkemedelshanteringen. Flera faktorer som påverkar hanteringen, bl a, avbrott och distraktioner, kunskap och kommunikation, har identifierats i studierna.Medication errors in somatic inpatient care are a serious threat to patient safety. Drug therapy is often an essential part of modern health care and an important responsibility for the nurse. The purpose of this study was to investigate witch factors that affect the patient safety during the nurse’s drug handling process in hospital settings. Nurse´s work environment can, in various ways, contribute to or counteract the safety of drug management thus multiple factors interact in this complex and dynamic environment. This study is a descriptive literature review with a systematic approach with the intent to compile and locate current research. Through database searches using PubMed and CHINAL relevant articles have been identified. The results based on ten different scientific studies show how multifactorial and dynamic the work environment of the nurse is and how this may affect patient safety during drug therapy. Several factors have been identified in studies that affect drug handling e g interruptions and distractions, knowledge and communication

    More or less of me and you: self-relevance augments the effects of item probability on stimulus prioritization

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    Self-relevance exerts a powerful influence on information processing. Compared to material associated with other people, personally meaningful stimuli are prioritized during decision-making. Further exploring the character of this effect, here we considered the extent to which stimulus enhancement is impacted by the frequency of self-relevant versus friend-relevant material. In a matching task, participants reported whether shape-label stimulus pairs corresponded to previously learned associations (e.g., triangle = self, square = friend). Crucially however, before the task commenced, stimulus-based expectancies were provided indicating the probability with which both self- and friend-related shapes would be encountered. The results revealed that task performance was impacted by the frequency of stimulus presentation in combination with the personal relevance of the items. When self- and friend-related shapes appeared with equal frequencies, a self-prioritization effect emerged (Expt. 1). Additionally, in both confirmatory (Expt. 2) and dis-confirmatory (Expt. 3) task contexts, stimuli that were encountered frequently (vs. infrequently) were prioritized, an effect that was most pronounced for self-relevant (vs. friend-relevant) items. Further computational analyses indicated that, in each of the reported experiments, differences in performance were underpinned by variation in the rate of information uptake, with evidence extracted more rapidly from self-relevant compared to friend-relevant stimuli. These findings advance our understanding of the emergence and origin of stimulus-prioritization effects during decisional processing. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00426-021-01562-x

    Mutation of the LUNATIC FRINGE Gene in Humans Causes Spondylocostal Dysostosis with a Severe Vertebral Phenotype

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    The spondylocostal dysostoses (SCDs) are a heterogeneous group of vertebral malsegmentation disorders that arise during embryonic development by a disruption of somitogenesis. Previously, we had identified two genes that cause a subset of autosomal recessive forms of this disease: DLL3 (SCD1) and MESP2 (SCD2). These genes are important components of the Notch signaling pathway, which has multiple roles in development and disease. Here, we have used a candidate-gene approach to identify a mutation in a third Notch pathway gene, LUNATIC FRINGE (LFNG), in a family with autosomal recessive SCD. LFNG encodes a glycosyltransferase that modifies the Notch family of cell-surface receptors, a key step in the regulation of this signaling pathway. A missense mutation was identified in a highly conserved phenylalanine close to the active site of the enzyme. Functional analysis revealed that the mutant LFNG was not localized to the correct compartment of the cell, was unable to modulate Notch signaling in a cell-based assay, and was enzymatically inactive. This represents the first known mutation in the human LFNG gene and reinforces the hypothesis that proper regulation of the Notch signaling pathway is an absolute requirement for the correct patterning of the axial skeleton
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