Τρίτη 3 Νοεμβρίου 2020

End-stage renal disease as a risk factor for epiglottitis

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Objectives

Patients with uremia are prone to infection; however, end-stage renal disease (ESRD) as a risk factor for acute epiglottitis warrants study. We investigated the risk of severe epiglottitis requiring hospitalisation in patients with ESRD.

Setting

We conducted a retrospective matched cohort study by using the claims data of Taiwan's National Health Insurance Research Database.

Participants

We identified an ESRD cohort with 87 908 patients newly diagnosed in 2000–2013 and underwent dialysis. The non-ESRD cohort comprised patients who had not received a diagnosis of ESRD, and they were matches to the ESRD cohort (1:1) by sex, age, residence urbanisation level, monthly income, and diabetes and hypertension status.

Primary and secondary outcome measures

The cumulative incidence of epiglottitis at the end of 2013 was analysed with Kaplan-Meier methods and log-rank tests. The HR of epiglottitis was calculated using the Cox proportional hazards model after adjustment for confounding factors.

Results

The overall epiglottitis incidence rate was 94% greater in the ESRD cohort than in the non-ESRD cohort (10.3 vs 5.3 cases per 100 000 person-years, p=0.002), with an adjusted HR of 1.89 (95% CI: 1.23 to 2.91, p=0.004). In the log-rank analysis, compared with the non-ESRD group, the epiglottitis cumulative incidence was significantly higher in the ESRD group (p=0.003). Epiglottitis did not exhibit an association with higher rates of airway interventions, intensive care unit admissions or longer hospitalisation in patients with ESRD than in controls.

Conclusions

This nationwide matched cohort study indicated that ESRD patients should be monitored for the risk of severe epiglottitis requiring hospitalisation.

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Δευτέρα 2 Νοεμβρίου 2020

Comparable human reconstitution following Cesium-137 versus X-ray irradiation preconditioning in immunodeficient NOG mice

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journal.pone.0241375.g005&size=inline

by Anna Halling Folkmar Andersen, Stine Sofie Frank Nielsen, Rikke Olesen, Jakob Le Fèvre Harslund, Ole Schmeltz Søgaard, Lars Østergaard, Paul W. Denton, Martin Tolstrup

Humanized mouse models are used extensively in research involving human pathogens and diseases. However, most of these models require preconditioning. Radio-active sources have been used routinely for this purpose but safety issues have motivated researchers to transition to chemical or X-ray based preconditioning. In this study, we directly compare 350 kV X-ray and Cs-137 low-dose precondition of NOG mice before human stem cell transplantation. Based on flow cytometry data, we found that engraftment of human cells into the mouse bone marrow was similar between radiation sources. Likewise, human engraftment in the peripheral blood was comparable between Cs-137 and three different X-ray doses with equal chimerization kinetics. In primary lymphoid organs such as the thymus and lymph nodes, and spleen, liver and lung, human-to-mouse chimerization was also comparable between irradiation sources. Development of different CD4 and CD8 T cells as well as these cells' maturation stages, i.e . from naïve to effector and memory subsets were generally analogous. Based on our results, we conclude that there are no discernable differences between the two sources in the low-dose spectrum investigated. However, while we encourage the transition to X-ray-based sources, we recommend all research groups to consider technical specifications and dose-finding studies.
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Development of the life change adaptation scale for family caregivers of individuals with acquired brain injury

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journal.pone.0241386.g001&size=inline

by Yuka Shindo, Etsuko Tadaka

Aim

Life changes due to the sudden onset of acquired brain injury (ABI) are drastic personal and social changes that require adaptation and are also an important indicator of the quality of life of family caregivers. However, there are no instruments for evaluating life change adaptation among family caregivers of individuals with acquired brain injury. This study aimed to develop the Life Change Adaptation Scale (LCAS) for family caregivers of individuals with ABI and examine its reliability and validity.

Methods

A cross-sectional study was conducted using a self-reported questionnaire. A total of 1622 family caregivers of individuals with ABI who belonged to 82 associations for families of individuals with ABI were selected as eligible participants. The construct validity was evaluated using a confirmatory factor analysis. Internal consistency was calculated using Cronbach's alpha. The K6 was also administered to assess the criterion-related validity of the LCAS.

Re sults

In total, 339 valid responses were received. The confirmatory factor analysis identified eight items from two domains, "Changes in the appraisal of caregiving resources" and "Changes in the health belief as a caregiver" (goodness of fit index = 0.963, adjusted goodness of fit index = 0.926, comparative fit index = 0.986, root mean square error of approximation  = 0.043.) Cronbach's alpha was 0.84. The LCAS was negatively correlated with the K6 (r = -0.504; P Conclusions

The LCAS is a brief, easy-to-administer instrument that is reliable and valid for family caregivers of individuals with ABI. This study contributes to the assessment and identification by family caregivers of individuals with ABI who require aid in adapting to life changes. Further research should be undertaken to verify the predictive value in a longitudinal study and to attempt to apply the LCAS to assess a broader range of subjects in a wider range of settings.

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Adult-onset temporal lobe epilepsy suspicious for autoimmune pathogenesis: Autoantibody prevalence and clinical correlates

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journal.pone.0241289.g004&size=inline

by Julia C. Kuehn, Carolin Meschede, Christoph Helmstaedter, Rainer Surges, Randi von Wrede, Elke Hattingen, Hartmut Vatter, Christian E. Elger, Susanne Schoch, Albert J. Becker, Julika Pitsch

Temporal lobe adult-onset seizures (TAOS) related to autoimmunity represent an increasingly recognized disease syndrome within the spectrum of epilepsies. In this context, certain autoantibodies (autoABs) were often associated with limbic encephalitis (LE). Here, we aimed to gain insights into (a) the distribution of 'neurological' autoABs (neuroABs, defined as autoABs targeting neuronal surface structures or 'onconeuronal' ABs or anti-glutamate acid decarboxylase 65 (GAD65) autoABs) in a large consecutive TAOS patient cohort, to characterize (b) clinical profiles of seropositive versus seronegative individuals and to find (c) potential evidence for other autoABs. Blood sera/cerebrospinal fluid (CSF) of TAOS patients (n = 800) and healthy donors (n = 27) were analyzed for neuroABs and screened for other autoABs by indirect immunofluorescence on hippocampal/cerebellar sections and immunoblots of whole brain and synaptosome lysates. Serological results were correlated with clin ico-neuropsychological features. 13% of TAOS patients (n = 105) were neuroAB+, with anti-GAD65 and anti-N-methyl-D-aspartate receptors (NMDAR) as most frequent autoABs in this group. In our screening tests 25% of neuroAB- patients (n = 199) were positive (screening+), whereas all control samples were negative (n = 27). Intriguingly, key clinico-neuropsychological characteristics including magnetic resonance imaging (MRI) findings, epileptiform electroencephalographic (EEG) activity, and inflammatory cellular infiltrates in CSF were shared to a greater extent by neuroAB+ with neuroAB-/screening+ patients than with neuroAB-/screening- patients. Serological testing in a large consecutive TAOS patient series revealed seropositivity for anti-GAD65 autoABs as the most frequent neuroAB. Intriguingly, neuroAB+ individuals were virtually indistinguishable from neuroAB-/screening + patients in several major clinical features. In contrast, neuroAB-/screening- TAOS patients differed in many parameters. These data support the potential presence of so far unrecognized autoABs in patients with TAOS.
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Prostate cancer survivors with symptoms of radiation cystitis have elevated fibrotic and vascular proteins in urine

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journal.pone.0241388.g004&size=inline

by Bernadette M. M. Zwaans, Heinz E. Nicolai, Michael B. Chancellor, Laura E. Lamb

Radiation for pelvic cancers can result in severe bladder damage and radiation cystitis (RC), which is characterized by chronic inflammation, fibrosis, and vascular damage. RC development is poorly understood because bladder biopsies are difficult to obtain. The goal of this study is to gain understanding of molecular changes that drive radiation-induced cystitis in cancer survivors using urine samples from prostate cancer survivors with history of radiation therapy. 94 urine samples were collected from prostate cancer survivors with (n = 85) and without (n = 9) history of radiation therapy. 15 patients with radiation history were officially diagnosed with radiation cystitis. Levels of 47 different proteins were measured using Multiplex Luminex. Comparisons were made between non-irradiated and irradiated samples, and within irradiated samples based on radiation cystitis diagnosis, symptom scores or hematuria. Statistical analysis was performed using Welch's t-test. In prostate canc er survivors with history of radiation therapy, elevated levels of PAI 1, TIMP1, TIMP2, HGF and VEGF-A were detected in patients that received a radiation cystitis diagnosis. These proteins were also increased in patients suffering from hematuria or high symptom scores. No inflammatory proteins were detected in the urine, except in patients with gross hematuria and end stage radiation cystitis. Active fibrosis and vascular distress is detectable in the urine through elevated levels of associated proteins. Inflammation is only detected in urine of patients with end-stage radiation cystitis disease. These results suggest that fibrosis and vascular damage drive the development of radiation cystitis and could lead to the development of more targeted treatments.
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Mesenchymal stem cells promote metastasis through activation of an ABL-MMP9 signaling axis in lung cancer cells

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journal.pone.0241423.g007&size=inline

by Jing Jin Gu, Jacob Hoj, Clay Rouse, Ann Marie Pendergast

Mesenchymal stem cells (MSCs) are recruited and activated by solid tumors and play a role in tumor progression and metastasis. Here we show that MSCs promote metastasis in a panel of non-small cell lung cancer (NSCLC) cells. MSCs elicit transcriptional alterations in lung cancer cells leading to increased expression of factors implicated in the epithelial-to-mesenchymal transition (EMT) and secreted proteins including matrix metalloproteinase-9 (MMP9). MSCs enhance secretion of enzymatically active MMP9 in a panel of lung adenocarcinoma cells. High expression of MMP9 is linked to low survival rates in lung adenocarcinoma patients. Notably, we found that ABL tyrosine kinases are activated in MSC-primed lung cancer cells and functional ABL kinases are required for MSC-induced MMP9 expression, secretion and proteolytic activity. Importantly, ABL kinases are required for MSC-induced NSCLC metastasis. These data reveal an actionable target for inhibiting MSC-induced metastatic acti vity of lung adenocarcinoma cells through disruption of an ABL kinase-MMP9 signaling axis activated in MSC-primed lung cancer cells.
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Comparative proteomic analysis of silica-induced pulmonary fibrosis

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journal.pone.0241310.g006&size=inline

by Cunxiang Bo, Xiao Geng, Juan Zhang, Linlin Sai, Yu Zhang, Gongchang Yu, Zhenling Zhang, Kai Liu, Zhongjun Du, Cheng Peng, Qiang Jia, Hua Shao

Silicosis is a systemic disease characterized by chronic persistent inflammation and incurable pulmonary fibrosis with the underlying molecular mechanisms to be fully elucidated. In this study, we employed tandem mass tag (TMT) based on quantitative proteomics technology to detect differentially expressed proteins (DEPs) in lung tissues of silica-exposed rats. A total of 285 DEPs (145 upregulated and 140 downregulated) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the biological pathway and functional classification of the proteins. Results showed that these DEPs were mainly enriched in the phagosome, lysosome function, complement and the coagulation cascade, glutathione metabolism, focal adhesion and ECM-receptor interactions. To validate the proteomics data, we selected and analyzed the expression trends of six proteins including CD14, PSAP, GM2A, COL1A1, ITGA8 and CLDN5 using parallel reaction monitoring ( PRM). The consistent result between PRM and TMT indicated the reliability of our proteomic data. These findings will help to reveal the pathogenesis of silicosis and provide potential therapeutic targets. Data are available via ProteomeXchange with identifier PXD020625.
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