Simulation of droplet-based microfluidic lab-on-a-chip applications

This paper was presented at the 3rd Micro and Nano Flows Conference (MNF2011), which was held at the Makedonia Palace Hotel, Thessaloniki in Greece. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, Aristotle University of Thessaloniki, University of Thessaly, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute.Miniaturization of biological and chemical assays in lab-on-a-chip systems is a highly topical field of research. Droplet-based microfluidic chips are types of these miniaturized systems. They expand the capability of assays with special features that are unreached by traditional workflows. In particular, small sample volumes, independent separated reaction units, high throughput, automation and parallelization of assays are prominent features of droplet-based microfluidic devices. Full custom centric design of droplet-based microfluidic lab-on-a-chip technology implicates a high system integration level and design complexity. Therefore advanced development methodologies are needed, comparable with the methods in electronic design automation. Our design and simulation toolkit meets these requirements for an agile and low-risk development of custom lab-on-a-chip devices. The system simulation approach enables a fast and precise prediction of complex microfluidic networks. This fact is confirmed by reference and benchmark experiments. The results show that the simulation correctly reproduces the experimental measurements.The German BMBF and the EU in the projects DiNaMiD, signature 0315591B and NoE Photonics4Life, Grant Agreement number: 224014

Embedding Ethical Impact Assessment in Nanosafety Decision Support

Nanotechnology is a key enabling technology, which is developing fast and influences many aspects of life. Nanomaterials are already included in a broad range of products and industrial sectors. Nanosafety issues are still a matter of concern for policy makers and stakeholders, but currently, there is no platform where all stakeholders can meet and discuss these issues. A comprehensive overview of all the issues in one single dashboard presenting the output of a decision support system is also lacking. This article outlines a strategy for developing one innovative part of a modular decision support system, designed to support the work of a new Risk Governance Council (RGC) for nanomaterials which will be established through the combined efforts of the GOV4NANO, NANORIGO, and RiskGONE H2020 projects. This new module will consist of guidelines for Ethical Impact Assessment (EIA) for nanomaterials and nanoenabled products. This article offers recommendations for adapting the European Committee for Standardization (CEN) prestandard on Ethical Impact Assessment CWA (CEN Workshop Agreement) 17145-2:2017 (E), to fit into the more-encompassing decision support system for risk governance of nanomaterials within the RiskGONE project

Gene transcripts associated with muscle strength: a CHARGE meta-analysis of 7,781 persons

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Background: Lower muscle strength in midlife predicts disability and mortality in later life. Bloodborne factors, including growth differentiation factor 11 (GDF11), have been linked to muscle regeneration in animal models. We aimed to identify gene transcripts associated with muscle strength in adults. Methods: Meta-analysis of whole blood gene expression (overall 17,534 unique genes measured by microarray) and hand-grip strength in four independent cohorts (n=7,781, ages: 20-104 years, weighted mean=56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, male/female). Results: Expression levels of 221 genes were associated with strength after adjustment for cofactors and for multiple statistical testing, including ALAS2 (rate limiting enzyme in heme synthesis), PRF1 (perforin, a cytotoxic protein associated with inflammation), IGF1R and IGF2BP2 (both insulin like growth factor related). We identified statistical enrichment for hemoglobin biosynthesis, innate immune activation and the stress response. Ten genes were only associated in younger individuals, four in males only and one in females only. For example PIK3R2 (a negative regulator of PI3K/AKT growth pathway) was negatively associated with muscle strength in younger (=60 years). We also show that 115 genes (52%) have not previously been linked to muscle in NCBI PubMed abstracts Conclusions: This first large-scale transcriptome study of muscle strength in human adults confirmed associations with known pathways and provides new evidence for over half of the genes identified. There may be age and sex specific gene expression signatures in blood for muscle strength.Wellcome TrustFHS gene expression profiling was funded through the Division of Intramural Research (Principal Investigator, Daniel Levy), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Dr. Murabito is supported by NIH grant R01AG029451. Dr. Kiel is supported by NIH R01 AR41398. The Framingham Heart Study is supported by National Heart, Lung, and Blood Institute contract N01-HC-25195.The InCHIANTI study was supported in part by the Intramural Research Program, National Institute on Aging, NIH, Baltimore MD USA. D.M. and L.W.H. were generously supported by a Wellcome Trust Institutional Strategic Support Award (WT097835MF). W.E.H. was funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health in EnglandThe infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-Mw, grant number 10-000-1002) and is supported by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Scientific Institute for Quality of Healthcare (IQ healthcare), Netherlands Institute for Health Services Research (NIVEL) and Netherlands Institute of Mental Health and Addiction (Trimbos Institute).The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93- 28 015; RIDE2), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of RNA-expression array data for the Rotterdam Study was executed and funded by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Netherlands. We thank Marjolein Peters, MSc, Ms. Mila Jhamai, Ms. Jeannette M. Vergeer-Drop, Ms. Bernadette van Ast-Copier, Mr. Marijn Verkerk and Jeroen van Rooij, BSc for their help in creating the RNA array expression databaseSHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald Approach to Individualized Medicine (GANI_MED)’ funded by the Federal Ministry of Education and Research (grant 03IS2061A). The University of Greifswald is a member of the 'Center of Knowledge Interchange' program of the Siemens AG and the Caché Campus program of the InterSystems GmbH

Risk Governance of Emerging Technologies Demonstrated in Terms of its Applicability to Nanomaterials

Nanotechnologies have reached maturity and market penetration that require nano-specific changes in legislation and harmonization among legislation domains, such as the amendments to REACH for nanomaterials (NMs) which came into force in 2020. Thus, an assessment of the components and regulatory boundaries of NMs risk governance is timely, alongside related methods and tools, as part of the global efforts to optimise nanosafety and integrate it into product design processes, via Safe(r)-by-Design (SbD) concepts. This paper provides an overview of the state-of-the-art regarding risk governance of NMs and lays out the theoretical basis for the development and implementation of an effective, trustworthy and transparent risk governance framework for NMs. The proposed framework enables continuous integration of the evolving state of the science, leverages best practice from contiguous disciplines and facilitates responsive re-thinking of nanosafety governance to meet future needs. To achieve and operationalise such framework, a science-based Risk Governance Council (RGC) for NMs is being developed. The framework will provide a toolkit for independent NMs' risk governance and integrates needs and views of stakeholders. An extension of this framework to relevant advanced materials and emerging technologies is also envisaged, in view of future foundations of risk research in Europe and globally

Calmodulin is responsible for Ca2+-dependent regulation of TRPA1 channels

TRPA1 is a Ca2+-permeable ion channel involved in many sensory disorders such as pain, itch and neuropathy. Notably, the function of TRPA1 depends on Ca2+, with low Ca2+ potentiating and high Ca2+ inactivating TRPA1. However, it remains unknown how Ca2+ exerts such contrasting effects. Here, we show that Ca2+ regulates TRPA1 through calmodulin, which binds to TRPA1 in a Ca2+-dependent manner. Calmodulin binding enhanced TRPA1 sensitivity and Ca2+-evoked potentiation of TRPA1 at low Ca2+, but inhibited TRPA1 sensitivity and promoted TRPA1 desensitization at high Ca2+. Ca2+-dependent potentiation and inactivation of TRPA1 were selectively prevented by disrupting the interaction of the carboxy-lobe of calmodulin with a calmodulin-binding domain in the C-terminus of TRPA1. Calmodulin is thus a critical Ca2+ sensor enabling TRPA1 to respond to diverse Ca2+ signals distinctly

Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review

<p>Abstract</p> <p>Background</p> <p>Over the past several decades, complementary and alternative medications have increasingly become a part of everyday treatment. With the rising cost of prescription medications and their production of unwanted side effects, patients are exploring herbal and other natural remedies for the management and treatment of psychological conditions. Psychological disorders are one of the most frequent conditions seen by clinicians, and often require a long-term regimen of prescription medications. Approximately 6.8 million Americans suffer from generalized anxiety disorder. Many also suffer from the spectrum of behavioural and physical side effects that often accompany its treatment. It is not surprising that there is universal interest in finding effective natural anxiolytic (anti-anxiety) treatments with a lower risk of adverse effects or withdrawal.</p> <p>Methods</p> <p>An electronic and manual search was performed through MEDLINE/PubMed and EBSCO. Articles were not discriminated by date of publication. Available clinical studies published in English that used human participants and examined the anxiolytic potential of dietary and herbal supplements were included. Data were extracted and compiled into tables that included the study design, sample population, intervention, control, length of treatment, outcomes, direction of evidence, and reported adverse events.</p> <p>Results</p> <p>A total of 24 studies that investigated five different CAM monotherapies and eight different combination treatments and involved 2619 participants met the inclusion criteria and were analyzed. There were 21 randomized controlled trials and three open-label, uncontrolled observational studies. Most studies involved patients who had been diagnosed with either an anxiety disorder or depression (n = 1786). However, eight studies used healthy volunteers (n = 877) who had normal levels of anxiety, were undergoing surgery, tested at the upper limit of the normal range of a trait anxiety scale, had adverse premenstrual symptoms or were peri-menopausal, reported anxiety and insomnia, or had one month or more of elevated generalized anxiety. Heterogeneity and the small number of studies for each supplement or combination therapy prevented a formal meta-analysis. Of the randomized controlled trials reviewed, 71% (15 out of 21) showed a positive direction of evidence. Any reported side effects were mild to moderate.</p> <p>Conclusions</p> <p>Based on the available evidence, it appears that nutritional and herbal supplementation is an effective method for treating anxiety and anxiety-related conditions without the risk of serious side effects. There is the possibility that any positive effects seen could be due to a placebo effect, which may have a significant psychological impact on participants with mental disorders. However, based on this systematic review, strong evidence exists for the use of herbal supplements containing extracts of passionflower or kava and combinations of L-lysine and L-arginine as treatments for anxiety symptoms and disorders. Magnesium-containing supplements and other herbal combinations may hold promise, but more research is needed before these products can be recommended to patients. St. John's wort monotherapy has insufficient evidence for use as an effective anxiolytic treatment.</p