4,170 research outputs found
Simultaneous bilateral aqueous misdirection following certolizumab therapy for rheumatoid arthritis
Aqueous misdirection syndrome is a rare, incompletely understood, sight-threatening eye condition that is difficult to diagnose and treat. We present a case of simultaneous bilateral aqueous misdirection following the administration of certolizumab in a 41-year-old women with rheumatoid arthritis and no known risk factors. To our knowledge, aqueous misdirection has not previously been associated with the use of tumour necrosis factor-alpha inhibitors.publishedVersio
World Wide Web Without Walls
Today's Web is built upon a particular symbiotic relationship betweensites and users: the sites invest capital to create and market a setof features, and users gain access to the sites often in exchange fortheir data (e.g., photos, personal information, creative musings,etc.). This paper imagines a very different Web ecosystem, in whichusers retain control of their data and developers can justify theirexistence without hoarding user data
Toward Secure Services from Untrusted Developers
We present a secure service prototype built from untrusted,contributed code.The service manages private data for a variety of different users, anduser programs frequently require access to other users' private data.However, aside from covert timing channels, no part of the service cancorrupt private data or leak it between users or outside the systemwithout permission from the data's owners.Instead, owners may choose to reveal their data in a controlled manner.This application model is demonstrated by Muenster, a job searchwebsite that protects both the integrity and secrecy of each user's data.In spite of running untrusted code, Muenster and other services canprevent overt leaks because the untrusted modules are constrained bythe operating system to follow pre-specified security policies, whichare nevertheless flexible enough for programmers to do useful work.We build Muenster atop Asbestos, a recently described operating systembased on a form of decentralized information flowcontrol
Health benefits of microalgae and their microbiomes
Microalgae comprise a phylogenetically very diverse group of photosynthetic unicellular pro- and eukaryotic organisms growing in marine and other aquatic environments. While they are well explored for the generation of biofuels, their potential as a source of antimicrobial and prebiotic substances have recently received increasing interest. Within this framework, microalgae may offer solutions to the societal challenge we face, concerning the lack of antibiotics treating the growing level of antimicrobial resistant bacteria and fungi in clinical settings. While the vast majority of microalgae and their associated microbiota remain unstudied, they may be a fascinating and rewarding source for novel and more sustainable antimicrobials and alternative molecules and compounds. In this review, we present an overview of the current knowledge on health benefits of microalgae and their associated microbiota. Finally, we describe remaining issues and limitation, and suggest several promising research potentials that should be given attention.publishedVersio
Implementing an interprofessional point-of-care ultrasound protocol for dyspneic patients in an emergency department as a blended learning concept—Feasibility of Employing Thoracic Ultrasound in Shortness of Breath
ObjectiveDyspnea is a common symptom in the Emergency Department, with a wide variety of differential diagnoses. Previous research has demonstrated the diagnostic accuracy of Point-of-Care Ultrasound (POCUS) in this field of interest. Our goal was to better establish sonography in our emergency department with a practicable and time effective method. Therefore, we implemented a sonography protocol in an interprofessional emergency team using blended learning as a modern didactic approach and evaluated the learning and teaching success. We named the study FETUS, which stands for “Feasibility of Employing Thoracic Ultrasound in Shortness of Breath.”MethodsA demonstration of the POCUS protocol was given, followed by individual supervision during clinical routine. A written manual, a pocket card, and further materials for personal training supplemented the training. A post-training questionnaire measured several parameters regarding the training, e.g., subjective skill-acquisition or media use.Results32 medical and nursing staff participated in this study, 14 of whom completed the questionnaire. All training modalities offered were well received. A pre-post comparison of subjective sonographic competence shows a significant increase in both medical and nursing staff.The other items surveyed also indicate the success of the intervention undertaken.ConclusionThe use of different media as a blended learning approach can support the implementation of new measures in the ongoing working routine within an interprofessional team
Adiponectin expression in patients with inflammatory cardiomyopathy indicates favourable outcome and inflammation control
Aims Circulating adiponectin (APN) is an immunomodulatory, pro-angiogenic, and anti-apoptotic adipocytokine protecting against acute viral heart disease and preventing pathological remodelling after cardiac injury. The purpose of this study was to describe the regulation and effects of APN in patients with inflammatory cardiomyopathy (DCMi). Methods and results Adiponectin expression and outcome were assessed in 173 patients with DCMi, 30 patients with non-inflammatory DCM, and 30 controls. Mechanistic background of these findings was addressed in murine experimental autoimmune myocarditis (EAM), a model of human DCMi, and further elucidated in vitro. Adiponectin plasma concentrations were significantly higher in DCMi compared with DCM or controls, i.e. 6.8 ± 3.9 µg/mL vs. 5.4 ± 3.6 vs. 4.76 ± 2.5 µg/mL (P< 0.05, respectively) and correlated significantly with cardiac mononuclear infiltrates (CD3+: r2= 0.025, P= 0.038; CD45R0+: r2= 0.058, P= 0.018). At follow-up, DCMi patients with high APN levels showed significantly increased left ventricular ejection fraction improvement, decreased left ventricular end-diastolic diameter, and reduced cardiac inflammatory infiltrates compared with patients with low APN levels. A multivariate linear regression analysis implicated APN as an independent prognostic factor for inhibition of cardiac inflammation. In accordance with these findings in human DCMi, EAM mice exhibited elevated plasma APN. Adiponectin gene transfer led to significant downregulation of key inflammatory mediators promoting disease. Mechanistically, APN acted as a negative regulator of T cells by reducing antigen specific expansion (P< 0.01) and suppressed TNFα-mediated NFκB activation (P< 0.01) as well as release of reactive oxygen species in cardiomyocytes. Conclusion Our results implicate that APN acts as endogenously upregulated anti-inflammatory cytokine confining cardiac inflammation and progression in DCM
ISO 50001: 2018 and Its Application in a Comprehensive Management System with an Energy-Performance Focus
[EN] Business progress and human development are linked to the efficient management of energy resources. The research in this paper contributes to the generalized application of good practices that reduce the vulnerability of companies. The research focuses on energy efficiency through comprehensive management systems (CMS), and "thought based on risks and opportunities", considering the discussion about the revision of ISO 50001:2018, the basic approach of the model and the route to implement CMS for quality, safety and health in the workplace, environmental management, energy efficiency, and other risk components. This implementation route, with the acronym CMS QHSE3+, places special emphasis on the functions of strategic planning, operational and risk management, and controls, as well as on deliverables and references to examples, templates, standards, and documents, to facilitate its application general in small and medium enterprises and in the management of energy efficiency.We express our gratitude for the support received, to CAJACOPI ATLÁNTICO, QUARA
Group, ASTEQ Technology, Simón Bolivar University, the Universitat Politècnica de València, SANTO TORIBIO
Business Group, and to all the personalities and companies who offered us their contributions and their valuable
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Maternal and infant outcomes associated with lithium use in pregnancy
Background Concerns about teratogenicity and offspring complications limit use of lithium in pregnancy. We aimed to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity and congenital malformations. Methods Meta-analysis of primary data analyzed using a shared protocol. Six study sites participated: Denmark, Canada, Netherlands, Sweden, UK, and US, totaling 727 lithium-exposed pregnancies compared to 21,397 reference pregnancies in mothers with a mood disorder, but unexposed to lithium. Main outcome measures included: (1) pregnancy complications, (2) delivery outcomes, (3) neonatal readmission to hospital within 28 days of birth, and (4) congenital malformations (major malformations and cardiac malformations). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were generated using logistic regression models. Site-specific prevalence rates and ORs were pooled using random-effects meta-analytic models. Findings Lithium exposure was not associated with any of the pre-defined pregnancy complications or delivery outcomes. There was an increased risk for neonatal readmission in lithium exposed (27·5%) versus reference group (14·3%) (Pooled aOR1·62; 95% CI: 1·12–2·33). Lithium exposure during first trimester was associated with increased risk of major malformations (7·4% versus 4·3%; pooled aOR 1·71, 95% CI: 1·07–2·72). Similarly, more lithium exposed children had major cardiac malformations, albeit not stasticially significant (2·1% versus 1·6%; pooled aOR 1·54, 95% CI: 0·64–3·70). Limitations in our study include: Serum lithium 5 levels were not available, hence no analyses related to dose-response effects could be performed, and residual confounding from e.g. substance abuse cannot be ruled out. Interpretation Treatment decisions must weigh the potential for increased risks, considering both effct sizes and the precision of the estimates, in particular associated with first-trimester lithium use against its effectiveness at reducing relapse
Causes and Consequences of A Glutamine Induced Normoxic HIF1 Activity for the Tumor Metabolism
The transcription factor hypoxia-inducible factor 1 (HIF1) is the crucial regulator of
genes that are involved in metabolism under hypoxic conditions, but information regarding the
transcriptional activity of HIF1 in normoxic metabolism is limited. Different tumor cells were treated
under normoxic and hypoxic conditions with various drugs that affect cellular metabolism. HIF1ff
was silenced by siRNA in normoxic/hypoxic tumor cells, before RNA sequencing and bioinformatics
analyses were performed while using the breast cancer cell line MDA-MB-231 as a model. Differentially
expressed genes were further analyzed and validated by qPCR, while the activity of the metabolites
was determined by enzyme assays. Under normoxic conditions, HIF1 activity was significantly
increased by (i) glutamine metabolism, which was associated with the release of ammonium, and
it was decreased by (ii) acetylation via acetyl CoA synthetase (ACSS2) or ATP citrate lyase (ACLY), respectively, and (iii) the presence of L-ascorbic acid, citrate, or acetyl-CoA. Interestingly, acetylsalicylic
acid, ibuprofen, L-ascorbic acid, and citrate each significantly destabilized HIF1ff only under normoxia.
The results from the deep sequence analyses indicated that, in HIF1-siRNA silenced MDA-MB-231
cells, 231 genes under normoxia and 1384 genes under hypoxia were transcriptionally significant
deregulated in a HIF1-dependent manner. Focusing on glycolysis genes, it was confirmed that HIF1
significantly regulated six normoxic and 16 hypoxic glycolysis-associated gene transcripts. However,
the results from the targeted metabolome analyses revealed that HIF1 activity affected neither the
consumption of glucose nor the release of ammonium or lactate; however, it significantly inhibited
the release of the amino acid alanine. This study comprehensively investigated, for the first time,
how normoxic HIF1 is stabilized, and it analyzed the possible function of normoxic HIF1 in the
transcriptome and metabolic processes of tumor cells in a breast cancer cell model. Furthermore, these
data imply that HIF1 compensates for the metabolic outcomes of glutaminolysis and, subsequently,
theWarburg effect might be a direct consequence of the altered amino acid metabolism in tumor cells
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