421 results on '"Pietro Ghezzi"'
Search Results
2. Use of immunology in news and YouTube videos in the context of COVID-19: politicisation and information bubbles
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Rachel Surrage George, Hannah Goodey, Maria Antonietta Russo, Rovena Tula, and Pietro Ghezzi
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COVID-19 ,YouTube ,news ,science communication ,scientific journalism ,health information ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundThe COVID-19 pandemic propelled immunology into global news and social media, resulting in the potential for misinterpreting and misusing complex scientific concepts.ObjectiveTo study the extent to which immunology is discussed in news articles and YouTube videos in English and Italian, and if related scientific concepts are used to support specific political or ideological narratives in the context of COVID-19.MethodsIn English and Italian we searched the period 11/09/2019 to 11/09/2022 on YouTube, using the software Mozdeh, for videos mentioning COVID-19 and one of nine immunological concepts: antibody-dependent enhancement, anergy, cytokine storm, herd immunity, hygiene hypothesis, immunity debt, original antigenic sin, oxidative stress and viral interference. We repeated this using MediaCloud for news articles.Four samples of 200 articles/videos were obtained from the randomised data gathered and analysed for mentions of concepts, stance on vaccines, masks, lockdown, social distancing, and political signifiers.ResultsVaccine-negative information was higher in videos than news (8-fold in English, 6-fold in Italian) and higher in Italian than English (4-fold in news, 3-fold in videos). We also observed the existence of information bubbles, where a negative stance towards one intervention was associated with a negative stance to other linked ideas. Some immunological concepts (immunity debt, viral interference, anergy and original antigenic sin) were associated with anti-vaccine or anti-NPI (non-pharmacological intervention) views. Videos in English mentioned politics more frequently than those in Italian and, in all media and languages, politics was more frequently mentioned in anti-guidelines and anti-vaccine media by a factor of 3 in video and of 3–5 in news.ConclusionThere is evidence that some immunological concepts are used to provide credibility to specific narratives and ideological views. The existence of information bubbles supports the concept of the “rabbit hole” effect, where interest in unconventional views/media leads to ever more extreme algorithmic recommendations.
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- 2024
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3. Editorial: Insights in inflammation: 2022
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Pietro Ghezzi, Rudolf Lucas, Simone Mader, Pierre Miossec, and Sandra Sacre
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inflammation ,signallig ,musculoskeletal diseases ,allergy ,transcription factors ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2023
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4. Editorial: Community series in translational insights into mechanisms and therapy of organ dysfunction in sepsis and trauma, volume II
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Borna Relja, Sina Maren Coldewey, Pietro Ghezzi, Lukas Martin, and Christoph Thiemermann
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sepsis ,trauma ,infections ,complications ,therapy ,outcome ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2023
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5. Perspective: Daniela Novick, cytokines and their receptors
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Pietro Ghezzi, Giamila Fantuzzi, and Charles A. Dinarello
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cytokines ,cytokine receptors ,cytokine antagonists ,antibodies ,interferon ,interleukin - 1 ,Immunologic diseases. Allergy ,RC581-607 - Abstract
This Perspective highlights the work of Dr. Daniela Novick in the field of cytokine biology. Using affinity chromatography to characterize cytokine-binding proteins, she identified soluble forms of the receptors as well as binding proteins for several cytokines, including tumor necrosis factor, interleukin (IL) 6, IL-18 and IL-32. Importantly, her work has been key in the development of monoclonal antibodies against interferons and cytokines. This Perspective discusses her contribution to the field and highlights her recent review on this topic.
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- 2023
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6. Online information on medical cannabis is not always aligned with scientific evidence and may raise unrealistic expectations
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Arthur Cassa Macedo, André Oliveira Vilela de Faria, Isabella Bizzi, Fabrício A. Moreira, Alessandro Colasanti, and Pietro Ghezzi
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Cannabis ,Health information ,Websites ,Consumer health information ,Pharmacy and materia medica ,RS1-441 ,Plant culture ,SB1-1110 - Abstract
Abstract Background There is a growing literature on the potential medical uses of Cannabis sativa and cannabinoid compounds. Although these have only been approved by regulatory agencies for a few indications, there is a hype about their possible benefits in a variety of conditions and a large market in the wellness industry. As in many cases patients search for information on cannabis products online, we have analyzed the information on medical cannabis available on the Internet. Therefore, this study aims at assessing the quality of the information available online on medical cannabis. Methods We searched “medical cannabis” on June 2019 using google.com and downloaded the first 243 websites. After excluding dead links or websites with no information about cannabis, 176 websites were included. They were then classified for their typology (e.g., commercial, government, news outlets). As an indicator of trustworthiness, we used the Journal of American Medical Association (JAMA) score, which assesses the indication of date, author, ownership of the website, and the presence of references. We also considered if a website is certified by Health-On-the-Net (HON), an independent organization, by displaying a HONCode symbol. Subsequently, we performed a content analysis to assess both the medical cannabis indications mentioned by webpages and the completeness of the information provided (whether they mentioned potential side effects and legal/regulatory issues or not). Results Analyzing 176 webpages returned by a search engine, we found that 52% of them were news websites. Pain, epilepsy, and multiple sclerosis were the most frequently mentioned therapeutic areas (cited in 92, 84 and 80 webpages, respectively), which did not always match those for which there is regulatory approval. Information was also incomplete, with only 22% of the webpages mentioning potential side effects. Health portal websites provided the most complete information, with all of them (n = 7) reporting side effects. On average, 80% of webpages had a neutral stance on the potential benefits of medical cannabis, with commercial websites having more frequently a positive stance (67%). Conclusions We conclude that the information that can be found online is not always aligned in terms of the therapeutic areas for which science-based evidence is often still weak.
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- 2022
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7. FRailty and Arterial stiffness – the role of oXidative stress and Inflammation (FRAXI study)
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Ekow Mensah, Khalid Ali, Winston Banya, Frances Ann Kirkham, Manuela Mengozzi, Pietro Ghezzi, and Chakravarthi Rajkumar
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Medicine (General) ,R5-920 - Abstract
Objective: There is an association between frailty and arterial stiffness. However, arterial stiffness does not uniformly correlate with the spectrum of frailty states. Both oxidative stress and inflammaging contribute to vascular ageing. There are no human studies exploring links between arterial stiffness, oxidative stress, inflammaging and frailty. Our objective is to investigate arterial stiffness and inflammaging as predictors of frailty states. Methods: An observational longitudinal cohort study will be used to examine the association between arterial stiffness, oxidative stress and inflammation in 50 older adults (⩾70 years) with clinical frailty scores (CFS) ⩽6 over 6 months. All study measurements will be taken at baseline. Frailty assessment will include hand-grip strength, timed-up and go test, mini-mental state examination, geriatric depression scale and sarcopenia using body composition measurements with Tanita ® . Arterial stiffness measurements will include carotid-femoral pulse wave velocity (cfPWV) and carotid-radial pulse wave velocity (crPWV) using Complior (Alam Medical, France). CAVI device will measure Cardio-ankle vascular index and ankle brachial index (ABI). Oxidative stress blood markers nitrotyrosine (NT) and 8-hydroxy-2’-deoxyguanosin (8-oxo-dG) and inflammation markers high-sensitive C-reactive protein (hs-CRP) and interlukin-6(IL-6) will be measured at baseline and 6 month along with lipid profile and glycated haemoglobin. Results (data analysis plan): Descriptive statistics for continuous data using means and standard deviations for normality distributed variables or medians and inter-quartile ranges for skewed variables will be used. Participants will be categorised into CFS 1-3, and CFS 4-6. Categorical data will use frequencies and comparison between groups. Change in frailty between the groups over 6 months will be compared using paired t-test. Simple linear regression will be done between frailty measures, arterial stiffness, inflammation and oxidative stress biomarkers. Significance will be at P < .05. Conclusion: This study data will inform a larger, multi-centre study exploring further the interplay between frailty, biomarkers and arterial stiffness parameters.
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- 2022
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8. Vitamins D3 and D2 have marked but different global effects on gene expression in a rat oligodendrocyte precursor cell line
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Manuela Mengozzi, Andrew Hesketh, Giselda Bucca, Pietro Ghezzi, and Colin P. Smith
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Myelination ,Multiple sclerosis ,Microarrays ,Cell differentiation ,Central glia-4 ,Therapeutics. Pharmacology ,RM1-950 ,Biochemistry ,QD415-436 - Abstract
Abstract Background Vitamin D deficiency increases the risk of developing multiple sclerosis (MS) but it is unclear whether vitamin D supplementation improves the clinical course of MS, and there is uncertainty about the dose and form of vitamin D (D2 or D3) to be used. The mechanisms underlying the effects of vitamin D in MS are not clear. Vitamin D3 increases the rate of differentiation of primary oligodendrocyte precursor cells (OPCs), suggesting that it might help remyelination in addition to modulating the immune response. Here we analyzed the transcriptome of differentiating rat CG4 OPCs treated with vitamin D2 or with vitamin D3 at 24 h and 72 h following onset of differentiation. Methods Gene expression in differentiating CG4 cells in response to vitamin D2 or D3 was quantified using Agilent DNA microarrays (n = 4 replicates), and the transcriptome data were processed and analysed using the R software environment. Differential expression between the experimental conditions was determined using LIMMA, applying the Benjamini and Hochberg multiple testing correction to p-values, and significant genes were grouped into co-expression clusters by hierarchical clustering. The functional significance of gene groups was explored by pathway enrichment analysis using the clusterProfiler package. Results Differentiation alone changed the expression of about 10% of the genes at 72 h compared to 24 h. Vitamin D2 and D3 exerted different effects on gene expression, with D3 influencing 1272 genes and D2 574 at 24 h. The expression of the vast majority of these genes was either not changed in differentiating cells not exposed to vitamin D or followed the same trajectory as the latter. D3-repressed genes were enriched for Gene Ontology (GO) categories including transcription factors and the Notch pathway, while D3-induced genes were enriched for the Ras pathway. Conclusions This study shows that vitamin D3, compared with D2, changes the expression of a larger number of genes in OLs. Identification of genes affected by D3 in OLs should help to identify mechanisms mediating its action in MS.
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- 2020
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9. The effect of radiofrequency electromagnetic fields (RF-EMF) on biomarkers of oxidative stress in vivo and in vitro: A protocol for a systematic review
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Bernd Henschenmacher, Annette Bitsch, Tonia de las Heras Gala, Henry Jay Forman, Athanassios Fragoulis, Pietro Ghezzi, Rupert Kellner, Wolfgang Koch, Jens Kuhne, Dmitrij Sachno, Gernot Schmid, Katya Tsaioun, Jos Verbeek, and Robert Wright
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SAR ,W/kg ,Oxidative stress ,Radiofrequency electromagnetic fields ,High frequency electromagnetic fields ,ROS ,Environmental sciences ,GE1-350 - Abstract
Background: Oxidative stress is conjectured to be related to many diseases. Furthermore, it is hypothesized that radiofrequency fields may induce oxidative stress in various cell types and thereby compromise human and animal health. This systematic review (SR) aims to summarize and evaluate the literature related to this hypothesis. Objectives: The main objective of this SR is to evaluate the associations between the exposure to radiofrequency electromagnetic fields and oxidative stress in experimental models (in vivo and in vitro). Methods: The SR framework has been developed following the guidelines established in the WHO Handbook for Guideline Development and the Handbook for Conducting a Literature-Based Health Assessment). We will include controlled in vivo and in vitro laboratory studies that assess the effects of an exposure to RF-EMF on valid markers for oxidative stress compared to no or sham exposure. The protocol is registered in PROSPERO.We will search the following databases: PubMed, Embase, Web of Science Core Collection, Scopus, and the EMF-Portal. The reference lists of included studies and retrieved review articles will also be manually searched. Study appraisal and synthesis method: Data will be extracted according to a pre-defined set of forms developed in the DistillerSR online software and synthesized in a meta-analysis when studies are judged sufficiently similar to be combined. If a meta-analysis is not possible, we will describe the effects of the exposure in a narrative way. Risk of bias: The risk of bias will be assessed with the NTP/OHAT risk of bias rating tool for human and animal studies.We will use GRADE to assess the certainty of the conclusions (high, moderate, low, or inadequate) regarding the association between radiofrequency electromagnetic fields and oxidative stress. Funding: This work was funded by the World Health Organization (WHO). Registration: The protocol was registered on the PROSPERO webpage on July 8, 2021.
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- 2022
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10. Redox regulation of immunity and the role of small molecular weight thiols
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Pietro Ghezzi
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Glutathione ,Innate immunity ,Nrf2 ,NF-kB ,HIF-1α ,Inflammation ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
It is thought that excessive production of reactive oxygen species (ROS) can be a causal component in many diseases, some of which have an inflammatory component. This led to an oversimplification whereby ROS are seen as inflammatory and antioxidants anti-inflammatory. This paper aims at reviewing some of the literature on thiols in host defense. The review will first summarize the mechanisms by which we survive infections by pathogens. Then we will consider how the redox field evolved from the concept of oxidative stress to that of redox regulation and how it intersects the field of innate immunity. A third section will analyze how an oversimplified oxidative stress theory of disease led to a hypothesis on the role of ROS and glutathione (GSH) in immunity, respectively as pro- and anti-inflammatory mediators. Finally, we will discuss some recent research and how to think out of the box of that oversimplification and link the role of thiols in redox regulation to the mechanisms by which we survive an infection outlined in the first section.
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- 2021
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11. Online information on face masks: analysis of websites in Italian and English returned by different search engines
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Pietro Ghezzi, Shaily Mehta, Daria Ghezzi, Alessia Catalani, and Tania Vanzolini
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Medicine - Abstract
Objective Countries have major differences in the acceptance of face mask use for the prevention of COVID-19. This work aims at studying the information online in different countries in terms of information quality and content.Design Content analysis.Method We analysed 450 webpages returned by searching the string ‘are face masks dangerous’ in Italy, the UK and the USA using three search engines (Bing, Duckduckgo and Google) in August 2020. The type of website and the stance about masks were assessed by two raters for each language and inter-rater agreement reported as Cohen’s kappa. The text of the webpages was collected from the web using WebBootCaT and analysed using a corpus analysis software to identify issues mentioned.Results Most pages were news outlets, and few (2%–6%) from public health agencies. Webpages with a negative stance on masks were more frequent in Italian (28%) than English (19%). Google returned the highest number of mask-positive pages and Duckduckgo the lowest. Google also returned the lowest number of pages mentioning conspiracy theories and Duckduckgo the highest. Webpages in Italian scored lower than those in English in transparency (reporting authors, their credentials and backing the information with references). When issues about the use of face masks were analysed, mask effectiveness was the most discussed followed by hypercapnia (accumulation of carbon dioxide), contraindication in respiratory disease and hypoxia, with issues related to their contraindications in mental health conditions and disability mentioned by very few pages.Conclusions This study suggests that: (1) public health agencies should increase their web presence in providing correct information on face masks; (2) search engines should improve the information quality criteria in their ranking; (3) the public should be more informed on issues related to the use of masks and disabilities, mental health and stigma arising for those people who cannot wear masks.
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- 2021
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12. Mitochondrial ROS, ER Stress, and Nrf2 Crosstalk in the Regulation of Mitochondrial Apoptosis Induced by Arsenite
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Orazio Cantoni, Ester Zito, Andrea Guidarelli, Mara Fiorani, and Pietro Ghezzi
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arsenic ,arsenite ,mitochondrial ROS ,endoplasmic reticulum stress ,toxicity ,Nrf2 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Long-term ingestion of arsenicals, a heterogeneous group of toxic compounds, has been associated with a wide spectrum of human pathologies, which include various malignancies. Although their mechanism of toxicity remains largely unknown, it is generally believed that arsenicals mainly produce their effects via direct binding to protein thiols and ROS formation in different subcellular compartments. The generality of these mechanisms most probably accounts for the different effects mediated by different forms of the metalloid in a variety of cells and tissues. In order to learn more about the molecular mechanisms of cyto- and genotoxicity, there is a need to focus on specific arsenic compounds under tightly controlled conditions. This review focuses on the mechanisms regulating the mitochondrial formation of ROS after exposure to low concentrations of a specific arsenic compound, NaAsO2, and their crosstalk with the nuclear factor (erythroid-2 related) factor 2 antioxidant signaling and the endoplasmic reticulum stress response.
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- 2022
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13. Automatic Identification of Information Quality Metrics in Health News Stories
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Majed Al-Jefri, Roger Evans, Joon Lee, and Pietro Ghezzi
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online health information ,machine learning ,health information quality assessment ,text classification ,natural language processing ,Public aspects of medicine ,RA1-1270 - Abstract
Objective: Many online and printed media publish health news of questionable trustworthiness and it may be difficult for laypersons to determine the information quality of such articles. The purpose of this work was to propose a methodology for the automatic assessment of the quality of health-related news stories using natural language processing and machine learning.Materials and Methods: We used a database from the website HealthNewsReview.org that aims to improve the public dialogue about health care. HealthNewsReview.org developed a set of criteria to critically analyze health care interventions' claims. In this work, we attempt to automate the evaluation process by identifying the indicators of those criteria using natural language processing-based machine learning on a corpus of more than 1,300 news stories. We explored features ranging from simple n-grams to more advanced linguistic features and optimized the feature selection for each task. Additionally, we experimented with the use of pre-trained natural language model BERT.Results: For some criteria, such as mention of costs, benefits, harms, and “disease-mongering,” the evaluation results were promising with an F1 measure reaching 81.94%, while for others the results were less satisfactory due to the dataset size, the need of external knowledge, or the subjectivity in the evaluation process.Conclusion: These used criteria are more challenging than those addressed by previous work, and our aim was to investigate how much more difficult the machine learning task was, and how and why it varied between criteria. For some criteria, the obtained results were promising; however, automated evaluation of the other criteria may not yet replace the manual evaluation process where human experts interpret text senses and make use of external knowledge in their assessment.
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- 2020
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14. Editorial: Medicine and Society
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Pietro Ghezzi, Arianne Shahvisi, and Hilde Stevens
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pseudoscience ,ethics ,health information ,genetic testing ,patient involvement ,Medicine (General) ,R5-920 - Published
- 2020
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15. Editorial: Translational Insights Into Mechanisms and Therapy of Organ Dysfunction in Sepsis and Trauma
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Peter Radermacher, Timothy R. Billiar, Pietro Ghezzi, Lukas Martin, and Christoph Thiemermann
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sepsis ,trauma ,multiple organ failure ,SIRS ,animal models ,translational studies ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2020
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16. Online Information of Vaccines: Information Quality, Not Only Privacy, Is an Ethical Responsibility of Search Engines
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Pietro Ghezzi, Peter G. Bannister, Gonzalo Casino, Alessia Catalani, Michel Goldman, Jessica Morley, Marie Neunez, Andreu Prados-Bo, Pierre R. Smeesters, Mariarosaria Taddeo, Tania Vanzolini, and Luciano Floridi
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search engines ,vaccines ,health information ,information quality ,privacy ,misinformation ,Medicine (General) ,R5-920 - Abstract
The fact that Internet companies may record our personal data and track our online behavior for commercial or political purpose has emphasized aspects related to online privacy. This has also led to the development of search engines that promise no tracking and privacy. Search engines also have a major role in spreading low-quality health information such as that of anti-vaccine websites. This study investigates the relationship between search engines' approach to privacy and the scientific quality of the information they return. We analyzed the first 30 webpages returned searching “vaccines autism” in English, Spanish, Italian, and French. The results show that not only “alternative” search engines (Duckduckgo, Ecosia, Qwant, Swisscows, and Mojeek) but also other commercial engines (Bing, Yahoo) often return more anti-vaccine pages (10–53%) than Google.com (0%). Some localized versions of Google, however, returned more anti-vaccine webpages (up to 10%) than Google.com. Health information returned by search engines has an impact on public health and, specifically, in the acceptance of vaccines. The issue of information quality when seeking information for making health-related decisions also impact the ethical aspect represented by the right to an informed consent. Our study suggests that designing a search engine that is privacy savvy and avoids issues with filter bubbles that can result from user-tracking is necessary but insufficient; instead, mechanisms should be developed to test search engines from the perspective of information quality (particularly for health-related webpages) before they can be deemed trustworthy providers of public health information.
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- 2020
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17. Environmental risk factors and their footprints in vivo – A proposal for the classification of oxidative stress biomarkers
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Pietro Ghezzi
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Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Environmental agents, including socioeconomic condition, and host factors can act as causal agents and risk factors in disease. We use biomarkers and sociomarkers to study causal factors, such as overproduction of reactive oxygen species (ROS) which could play a role in disease through oxidative stress. It is therefore important to define the exact meaning of the biomarker we measure. In this review we attempt a classification of biomarkers related to oxidative stress based on their biological meaning. We define as type zero biomarkers the direct measurement of ROS in vivo in patients. Type 1 biomarkers are the most frequently used indicators of oxidative stress, represented by oxidized lipids, proteins or nucleic acids and their bases. Type 2 biomarkers are indicators of the activation of biochemical pathways that can lead to the formation of ROS. Type 3 biomarkers are host factors such as small-molecular weight antioxidants and antioxidant enzymes, while type 4 biomarkers measure genetic factors and mutations that could modify the susceptibility of an individual to oxidative stress. We also discuss whether biomarkers are actionable or not, that is if the specific blockade of these molecules can ameliorate disease or if they are just surrogate markers.The proposed classification of biomarkers of oxidative stress based on their meaning and ambiguities, within the theoretical framework of the oxidative stress theory of disease may help identify those diseases, and individuals, where oxidative stress has a causal role, to allow targeted therapy and personalized medicine.
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- 2020
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18. C-Reactive Protein Predicts Further Ischemic Events in Patients With Transient Ischemic Attack or Lacunar Stroke
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Manuela Mengozzi, Frances A. Kirkham, Esme E. R. Girdwood, Eva Bunting, Erin Drazich, Jean Timeyin, Pietro Ghezzi, and Chakravarthi Rajkumar
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TIA ,lacunar stroke ,cerebral ischemia ,inflammation ,oxidative stress ,CRP ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Patients who have experienced a first cerebral ischemic event are at increased risk of recurrent stroke. There is strong evidence that low-level inflammation as measured by high sensitivity C-reactive protein (hs-CRP) is a predictor of further ischemic events. Other mechanisms implicated in the pathogenesis of stroke may play a role in determining the risk of secondary events, including oxidative stress and the adaptive response to it and activation of neuroprotective pathways by hypoxia, for instance through induction of erythropoietin (EPO). This study investigated the association of the levels of CRP, peroxiredoxin 1 (PRDX1, an indicator of the physiological response to oxidative stress) and EPO (a neuroprotective factor produced in response to hypoxia) with the risk of a second ischemic event. Eighty patients with a diagnosis of lacunar stroke or transient ischemic attack (TIA) were included in the study and a blood sample was collected within 14 days from the initial event. Hs-CRP, PRDX1, and EPO were measured by ELISA. Further ischemic events were recorded with a mean follow-up of 42 months (min 24, max 64). Multivariate analysis showed that only CRP was an independent predictor of further events with an observed risk (OR) of 1.14 (P = 0.034, 95% CI 1.01–1.29). No association was observed with the levels of PRDX1 or EPO. A receiver operating curve (ROC) determined a cut-off CRP level of 3.25 μg/ml, with a 46% sensitivity and 81% specificity. Low-level inflammation as detected by hs-CRP is an independent predictor of recurrent cerebrovascular ischemic events.
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- 2020
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19. Editorial: Dimensions of Health Information Quality
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Pietro Ghezzi and Elizabeth Ford
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health records ,patient data ,websites ,social media ,literacy ,Public aspects of medicine ,RA1-1270 - Published
- 2020
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20. Online Information on Probiotics: Does It Match Scientific Evidence?
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Marie Neunez, Michel Goldman, and Pietro Ghezzi
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probiotics ,safety ,regulatory ,health claims ,online ,evidence-based medicine ,Medicine (General) ,R5-920 - Abstract
Probiotics are over-the-counter products marketed for enhancing human health. Online information has been key in promoting probiotics worldwide. However, only few rigorous clinical studies have met the stringent criteria required to establish the efficacy and safety of probiotics. The present study was undertaken to assess the information quality of webpages referring to probiotics and to compare the recommendations available online with the information collected from trusted scientific sources. We evaluated 150 webpages returned by Google searching “probiotics” in terms of typology of website, health information quality based on the JAMA score and the HONcode certification, as well as completeness of the information based on the presence of four criteria: (1) links to scientific references supporting health claims, (2) cautionary notes about level of evidence for alleged benefits, (3) safety considerations, and (4) regulatory status. We then enumerated the health claims mentioned online and the corresponding clinical trials and reviews registered in the Cochrane library. Finally, the conclusions of Cochrane reviews were used to assess the level of scientific evidence of the information available through Google search. HON-certified websites were significantly more frequent in the top 10 websites than in the remaining websites. In terms of completeness of information, only 10% of webpages met all four criteria, 40% had a cautionary note on benefits, 35% referred to scientific literature, and only 25% mentioned potential side effects. The results of the content analysis led us to conclude that: (1) the most frequent typologies of webpages returned by Google are commercial and news, (2) commercial websites on average provide the least reliable information, and (3) significant numbers of claimed benefits of probiotics are not supported by scientific evidence. This study highlights important biases in the probiotics information available online, underlining the need to improve the quality and objectivity of information provided to the public.
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- 2020
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21. Leukemia inhibitory factor inhibits erythropoietin-induced myelin gene expression in oligodendrocytes
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Georgina Gyetvai, Cieron Roe, Lamia Heikal, Pietro Ghezzi, and Manuela Mengozzi
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Central glia-4 ,Multiple sclerosis ,Myelin oligodendrocyte glycoprotein ,SOCS3 ,TLR2 ,Therapeutics. Pharmacology ,RM1-950 ,Biochemistry ,QD415-436 - Abstract
Abstract Background The pro-myelinating effects of leukemia inhibitory factor (LIF) and other cytokines of the gp130 family, including oncostatin M (OSM) and ciliary neurotrophic factor (CNTF), have long been known, but controversial results have also been reported. We recently overexpressed erythropoietin receptor (EPOR) in rat central glia-4 (CG4) oligodendrocyte progenitor cells (OPCs) to study the mechanisms mediating the pro-myelinating effects of erythropoietin (EPO). In this study, we investigated the effect of co-treatment with EPO and LIF. Methods Gene expression in undifferentiated and differentiating CG4 cells in response to EPO and LIF was analysed by DNA microarrays and by RT-qPCR. Experiments were performed in biological replicates of N ≥ 4. Functional annotation and biological term enrichment was performed using DAVID (Database for Annotation, Visualization and Integrated Discovery). The gene-gene interaction network was visualised using STRING (Search Tool for the Retrieval of Interacting Genes). Results In CG4 cells treated with 10 ng/ml of EPO and 10 ng/ml of LIF, EPO-induced myelin oligodendrocyte glycoprotein (MOG) expression, measured at day 3 of differentiation, was inhibited ≥4-fold (N = 5, P
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- 2018
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22. Assessment of HIF-1α expression and release following endothelial injury in-vitro and in-vivo
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Lamia Heikal, Pietro Ghezzi, Manuela Mengozzi, and Gordon Ferns
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HIF-1α ,Injury ,Endothelial cells ,ELISA ,Angioplasty ,Therapeutics. Pharmacology ,RM1-950 ,Biochemistry ,QD415-436 - Abstract
Abstract Background Endothelial injury is an early and enduring feature of cardiovascular disease. Inflammation and hypoxia may be responsible for this, and are often associated with the up-regulation of several transcriptional factors that include Hypoxia Inducible Factor-1 (HIF-1). Although it has been reported that HIF-1α is detectable in plasma, it is known to be unstable. Our aim was to optimize an assay for HIF-1α to be applied to in vitro and in vivo applications, and to use this assay to assess the release kinetics of HIF-1α following endothelial injury. Methods An ELISA for the measurement of HIF-1α in cell-culture medium and plasma was optimized, and the assay was used to determine the best conditions for sample collection and storage. The results of the ELISA were validated using Western blotting and immunohistochemistry (IHC). In vitro, a standardized injury was produced in a monolayer of rat aortic endothelial cells (RAECs) and intracellular HIF-1α was measured at intervals over 24 h. In vivo, a rat angioplasty model was used. The right carotid artery was injured using a 2F Fogarty balloon catheter. HIF-1α was measured in the plasma and in the arterial tissue (0, 1, 2, 3 and 5 days post injury). Results The HIF-1α ELISA had a limit of detection of 2.7 pg/mL and was linear up to 1000 pg/ mL. Between and within-assay, the coefficient of variation values were less than 15%. HIF-1α was unstable in cell lysates and plasma, and it was necessary to add a protease inhibitor immediately after collection, and to store samples at -80 °C prior to analysis. The dynamics of HIF-1α release were different for the in vitro and in vivo models. In vitro, HIF-1α reached maximum concentrations approximately 2 h post injury, whereas peak values in plasma and tissues occurred approximately 2 days post injury, in the balloon injury model. Conclusion HIF-1α can be measured in plasma, but this requires careful sample collection and storage. The carotid artery balloon injury model is associated with the transient release of HIF-1α into the circulation that probably reflects the hypoxia induced in the artery wall.
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- 2018
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23. European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)
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Javier Egea, Isabel Fabregat, Yves M. Frapart, Pietro Ghezzi, Agnes Görlach, Thomas Kietzmann, Kateryna Kubaichuk, Ulla G. Knaus, Manuela G. Lopez, Gloria Olaso-Gonzalez, Andreas Petry, Rainer Schulz, Jose Vina, Paul Winyard, Kahina Abbas, Opeyemi S. Ademowo, Catarina B. Afonso, Ioanna Andreadou, Haike Antelmann, Fernando Antunes, Mutay Aslan, Markus M. Bachschmid, Rui M. Barbosa, Vsevolod Belousov, Carsten Berndt, David Bernlohr, Esther Bertrán, Alberto Bindoli, Serge P. Bottari, Paula M. Brito, Guia Carrara, Ana I. Casas, Afroditi Chatzi, Niki Chondrogianni, Marcus Conrad, Marcus S. Cooke, João G. Costa, Antonio Cuadrado, Pham My-Chan Dang, Barbara De Smet, Bilge Debelec–Butuner, Irundika H.K. Dias, Joe Dan Dunn, Amanda J. Edson, Mariam El Assar, Jamel El-Benna, Péter Ferdinandy, Ana S. Fernandes, Kari E. Fladmark, Ulrich Förstermann, Rashid Giniatullin, Zoltán Giricz, Anikó Görbe, Helen Griffiths, Vaclav Hampl, Alina Hanf, Jan Herget, Pablo Hernansanz-Agustín, Melanie Hillion, Jingjing Huang, Serap Ilikay, Pidder Jansen-Dürr, Vincent Jaquet, Jaap A. Joles, Balaraman Kalyanaraman, Danylo Kaminskyy, Mahsa Karbaschi, Marina Kleanthous, Lars-Oliver Klotz, Bato Korac, Kemal Sami Korkmaz, Rafal Koziel, Damir Kračun, Karl-Heinz Krause, Vladimír Křen, Thomas Krieg, João Laranjinha, Antigone Lazou, Huige Li, Antonio Martínez-Ruiz, Reiko Matsui, Gethin J. McBean, Stuart P. Meredith, Joris Messens, Verónica Miguel, Yuliya Mikhed, Irina Milisav, Lidija Milković, Antonio Miranda-Vizuete, Miloš Mojović, María Monsalve, Pierre-Alexis Mouthuy, John Mulvey, Thomas Münzel, Vladimir Muzykantov, Isabel T.N. Nguyen, Matthias Oelze, Nuno G. Oliveira, Carlos M. Palmeira, Nikoletta Papaevgeniou, Aleksandra Pavićević, Brandán Pedre, Fabienne Peyrot, Marios Phylactides, Gratiela G. Pircalabioru, Andrew R. Pitt, Henrik E. Poulsen, Ignacio Prieto, Maria Pia Rigobello, Natalia Robledinos-Antón, Leocadio Rodríguez-Mañas, Anabela P. Rolo, Francis Rousset, Tatjana Ruskovska, Nuno Saraiva, Shlomo Sasson, Katrin Schröder, Khrystyna Semen, Tamara Seredenina, Anastasia Shakirzyanova, Geoffrey L. Smith, Thierry Soldati, Bebiana C. Sousa, Corinne M. Spickett, Ana Stancic, Marie José Stasia, Holger Steinbrenner, Višnja Stepanić, Sebastian Steven, Kostas Tokatlidis, Erkan Tuncay, Belma Turan, Fulvio Ursini, Jan Vacek, Olga Vajnerova, Kateřina Valentová, Frank Van Breusegem, Lokman Varisli, Elizabeth A. Veal, A. Suha Yalçın, Olha Yelisyeyeva, Neven Žarković, Martina Zatloukalová, Jacek Zielonka, Rhian M. Touyz, Andreas Papapetropoulos, Tilman Grune, Santiago Lamas, Harald H.H.W. Schmidt, Fabio Di Lisa, and Andreas Daiber
- Subjects
Reactive oxygen species ,Reactive nitrogen species ,Redox signaling ,Oxidative stress ,Antioxidants ,Redox therapeutics ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.
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- 2017
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24. Corrigendum: Fake News or Weak Science? Visibility and Characterization of Antivaccine Webpages Returned by Google in Different Languages and Countries
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Nadia Arif, Majed Al-Jefri, Isabella Harb Bizzi, Gianni Boitano Perano, Michel Goldman, Inam Haq, Kee Leng Chua, Manuela Mengozzi, Marie Neunez, Helen Smith, and Pietro Ghezzi
- Subjects
information quality ,google ,Internet ,news ,news media ,vaccines ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2019
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25. Boosting the Immune System, From Science to Myth: Analysis the Infosphere With Google
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Arthur Cassa Macedo, André Oliveira Vilela de Faria, and Pietro Ghezzi
- Subjects
internet ,immunity ,vaccines ,antioxidants ,google ,vitamins ,Medicine (General) ,R5-920 - Abstract
Background: The concept that one can “boost” immunity is a popular one. Although the only evidence-based approach to this is vaccination, the lay public is exposed to a wide range of information on how to boost immunity. The aim of this study was to analyze such information available on the Internet.Methods and findings: We visited 185 webpages returned from a Google search on “boost immunity” and classified them by typology (blogs, commercial, government, no-profit, news, professional, scientific journals) and by using standard indicators of health information quality (JAMA score, HONCode). We then analyzed their content in terms of disease and “boosters” mentioned. Commercial and news websites represented one third of the results each. Of the 37 approaches to boost immunity recorded, the top ones were diet (77% of webpages), fruit (69%), vitamins (67%), antioxidants (52%), probiotics (51%), minerals (50%), and vitamin C (49%). Interestingly, vaccines ranked 27th, with only 12% of webpages mentioning them.Conclusions: Commercial websites are an important component of the information available to the public on the topic, and thus contribute providing biased information.
- Published
- 2019
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26. Secretion of IL-1β From Monocytes in Gout Is Redox Independent
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Ben M. Alberts, Connor Bruce, Kolitha Basnayake, Pietro Ghezzi, Kevin A. Davies, and Lisa M. Mullen
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IL-1β ,gout ,chronic kidney disease ,NLRP3 inflammasome ,antioxidant capacity ,redox regulation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The pro-inflammatory cytokine interleukin-1β (IL-1β) plays important roles in immunity but is also implicated in autoimmune disease. The most well-established mechanism of IL-1β secretion is via activation of the NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome which requires an initial priming signal followed by an activating signal. However, the precise mechanism by which the inflammasome is activated remains unclear. The role of reactive oxygen species (ROS) in this process is contradictory, with some studies suggesting that ROS are crucial while others describe opposite effects. In this study, we evaluated the effects of oxidative stress on IL-1β secretion. Gout is a disease driven solely by IL-1β secretion in response to monosodium urate (MSU) crystals which form during periods of hyperuricemia and thus presents an opportunity to study factors contributing to IL-1β secretion. Sera and monocytes were isolated from patients with gout to determine whether differences in antioxidant status could explain the susceptibility of these individuals to gout attacks. In addition, sera and monocytes were collected from patients with chronic kidney disease (CKD) for comparison as this condition is associated with high levels of oxidative stress and disturbances in serum uric acid levels. There were differences in some aspects of antioxidant defenses in gout patients and these were mainly due to higher serum uric acid. Monocytes from gout patients were more responsive to priming, but not activation, of the NLRP3 inflammasome. However, expression of the components of the NLRP3 inflammasome were unaffected by priming or activation of the inflammasome, nor were these expression levels differentially regulated in gout patients. Inhibition of ROS by N-Acetyl Cysteine inhibited TLR2-induced priming of the NLRP3 inflammasome, but had no effect on MSU-induced activation. Together these findings demonstrate that oxidative stress only affects priming of the NLRP3 inflammasome but does not influence activation.
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- 2019
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27. Correction to: Leukemia inhibitory factor inhibits erythropoietin-induced myelin gene expression in oligodendrocytes
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Georgina Gyetvai, Cieron Roe, Lamia Heikal, Pietro Ghezzi, and Manuela Mengozzi
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Therapeutics. Pharmacology ,RM1-950 ,Biochemistry ,QD415-436 - Abstract
An amendment to this paper has been published and can be accessed via the original article.
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- 2020
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28. Correction to: Assessment of HIF-1α expression and release following endothelial injury in-vitro and in-vivo
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Lamia Heikal, Pietro Ghezzi, Manuela Mengozzi, and Gordon Ferns
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Therapeutics. Pharmacology ,RM1-950 ,Biochemistry ,QD415-436 - Abstract
An amendment to this paper has been published and can be accessed via the original article.
- Published
- 2020
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29. What Is Health Information Quality? Ethical Dimension and Perception by Users
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Majed Al-Jefri, Roger Evans, Gulden Uchyigit, and Pietro Ghezzi
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internet ,information quality ,ethics ,online information ,public health ,Medicine (General) ,R5-920 - Abstract
Introduction: The popularity of seeking health information online makes information quality (IQ) a public health issue. The present study aims at building a theoretical framework of health information quality (HIQ) that can be applied to websites and defines which IQ criteria are important for a website to be trustworthy and meet users' expectations.Methods: We have identified a list of HIQ criteria from existing tools and assessment criteria and elaborated them into a questionnaire that was promoted via social media and mainly the University. Responses (329) were used to rank the different criteria for their importance in trusting a website and to identify patterns of criteria using hierarchical cluster analysis.Results: HIQ criteria were organized in five dimensions based on previous theoretical frameworks as well as on how they cluster together in the questionnaire response. We could identify a top-ranking dimension (scientific completeness) that describes what the user is expecting to know from the websites (in particular: description of symptoms, treatments, side effects). Cluster analysis also identified a number of criteria borrowed from existing tools for assessing HIQ that could be subsumed to a broad “ethical” dimension (such as conflict of interests, privacy, advertising policies) that were, in general, ranked of low importance by the participants. Subgroup analysis revealed significant differences in the importance assigned to the various criteria based on gender, language and whether or not of biomedical educational background.Conclusions: We identified criteria of HIQ and organized them in dimensions. We observed that ethical criteria, while regarded highly in the academic and medical environment, are not considered highly by the public.
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- 2018
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30. 3D Bioprinting of Novel Biocompatible Scaffolds for Endothelial Cell Repair
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Yan Wu, Lamia Heikal, Gordon Ferns, Pietro Ghezzi, Ali Nokhodchi, and Mohammed Maniruzzaman
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3d bioprinting ,biocompatible ,endothelial cell ,dmog ,epo ,scaffolds ,polylactic acid ,Organic chemistry ,QD241-441 - Abstract
The aim of this study was to develop and evaluate an optimized 3D bioprinting technology in order to fabricate novel scaffolds for the application of endothelial cell repair. Various biocompatible and biodegradable macroporous scaffolds (D = 10 mm) with interconnected pores (D = ~500 µm) were fabricated using a commercially available 3D bioprinter (r3bEL mini, SE3D, USA). The resolution of the printing layers was set at ~100 µm for all scaffolds. Various compositions of polylactic acid (PLA), polyethylene glycol (PEG) and pluronic F127 (F127) formulations were prepared and optimized to develop semi-solid viscous bioinks. Either dimethyloxalylglycine (DMOG) or erythroprotein (EPO) was used as a model drug and loaded in the viscous biocompatible ink formulations with a final concentration of 30% (w/w). The surface analysis of the bioinks via a spectroscopic analysis revealed a homogenous distribution of the forming materials throughout the surface, whereas SEM imaging of the scaffolds showed a smooth surface with homogenous macro-porous texture and precise pore size. The rheological and mechanical analyses showed optimum rheological and mechanical properties of each scaffold. As the drug, DMOG, is a HIF-1 inducer, its release from the scaffolds into PBS solution was measured indirectly using a bioassay for HIF-1α. This showed that the release of DMOG was sustained over 48 h. The release of DMOG was enough to cause a significant increase in HIF-1α levels in the bioassay, and when incubated with rat aortic endothelial cells (RAECs) for 2 h resulted in transcriptional activation of a HIF-1α target gene (VEGF). The optimum time for the increased expression of VEGF gene was approximately 30 min and was a 3-4-fold increase above baseline. This study provides a proof of concept, that a novel bioprinting platform can be exploited to develop biodegradable composite scaffolds for potential clinical applications in endothelial cell repair in cardiovascular disease (CVD), or in other conditions in which endothelial damage occurs.
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- 2019
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31. Fake News or Weak Science? Visibility and Characterization of Antivaccine Webpages Returned by Google in Different Languages and Countries
- Author
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Nadia Arif, Majed Al-Jefri, Isabella Harb Bizzi, Gianni Boitano Perano, Michel Goldman, Inam Haq, Kee Leng Chua, Manuela Mengozzi, Marie Neunez, Helen Smith, and Pietro Ghezzi
- Subjects
information quality ,google ,Internet ,news ,news media ,vaccines ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The 1998 Lancet paper by Wakefield et al., despite subsequent retraction and evidence indicating no causal link between vaccinations and autism, triggered significant parental concern. The aim of this study was to analyze the online information available on this topic. Using localized versions of Google, we searched “autism vaccine” in English, French, Italian, Portuguese, Mandarin, and Arabic and analyzed 200 websites for each search engine result page (SERP). A common feature was the newsworthiness of the topic, with news outlets representing 25–50% of the SERP, followed by unaffiliated websites (blogs, social media) that represented 27–41% and included most of the vaccine-negative websites. Between 12 and 24% of websites had a negative stance on vaccines, while most websites were pro-vaccine (43–70%). However, their ranking by Google varied. While in Google.com, the first vaccine-negative website was the 43rd in the SERP, there was one vaccine-negative webpage in the top 10 websites in both the British and Australian localized versions and in French and two in Italian, Portuguese, and Mandarin, suggesting that the information quality algorithm used by Google may work better in English. Many webpages mentioned celebrities in the context of the link between vaccines and autism, with Donald Trump most frequently. Few websites (1–5%) promoted complementary and alternative medicine (CAM) but 50–100% of these were also vaccine-negative suggesting that CAM users are more exposed to vaccine-negative information. This analysis highlights the need for monitoring the web for information impacting on vaccine uptake.
- Published
- 2018
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32. Severity of Systemic Inflammatory Response Syndrome Affects the Blood Levels of Circulating Inflammatory-Relevant MicroRNAs
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Stefano Caserta, Manuela Mengozzi, Florian Kern, Sarah F. Newbury, Pietro Ghezzi, and Martin J. Llewelyn
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systemic inflammatory response syndrome ,sepsis ,microRNA ,inflammation ,immune cells ,sequential organ failure assessment score ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The systemic inflammatory response syndrome (SIRS) is a potentially lethal response triggered by diverse forms of tissue injury and infection. When systemic inflammation is triggered by infection, the term sepsis is used. Understanding how inflammation is mediated and regulated is of enormous medical importance. We previously demonstrated that circulating inflammatory-relevant microRNAs (CIR-miRNAs) are candidate biomarkers for differentiating sepsis from SIRS. Here, we set out to determine how CIR-miRNA levels reflect SIRS severity and whether they derive from activated immune cells. Clinical disease severity scores and markers of red blood cell (RBC) damage or immune cell activation were correlated with CIR-miRNA levels in patients with SIRS and sepsis. The release of CIR-miRNAs modulated during SIRS was assessed in immune cell cultures. We show that severity of non-infective SIRS, but not sepsis is reflected in the levels of miR-378a-3p, miR-30a-5p, miR-30d-5p, and miR-192-5p. These CIR-miRNA levels positively correlate with levels of the redox biomarker, peroxiredoxin-1 (Prdx-1), which has previously been shown to be released by immune cells during inflammation. Furthermore, in vitro activated immune cells produce SIRS-associated miR-378a-3p, miR-30a-5p, miR-30d-5p, and miR-192-5p. Our study furthers the understanding of the origin, role, and trafficking of CIR-miRNAs as potential regulators of inflammation.
- Published
- 2018
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33. P30 THE ROLE OF NOVEL BIOMARKERS IN ARTERIAL STIFFNESS, AND IN PREDICTING FURTHER VASCULAR EVENTS AFTER TIA AND LACUNAR STROKE
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Esme Girdwood, Manuela Mengozzi, Eva Bunting, Jean Timeyin, Pietro Ghezzi, and Chakravarthi Rajkumar
- Subjects
Specialties of internal medicine ,RC581-951 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Objective: To explore the role of biomarkers (hsCRP, sRANKL, PRDX1 and EPO) in arterial stiffness and in predicting further vascular events. Methods: Patients from the ongoing ASIST study each attended a laboratory visit within fourteen days of their diagnosed TIA or lacunar stroke. Arterial stiffness was calculated using cfPWV (carotid-femoral pulse wave velocity) measured with Complior ®Artech, France, and with the CAVI ®Fukuda, Japan (cardio-ankle vascular index) method. Blood samples were taken for ELISA assays. Analysis was completed with SPSS software Results: Forty patients were evaluated in this preliminary project (29 male/11 female, mean age 70.7±11.99), with four experiencing a further event during the six month follow up (10%). All biomarkers and both measurements for arterial stiffness had a higher mean value in patients with a further event (hsCRP 3.89 vs 1.42, P = 0.08; EPO 9.06 vs 9.01, P = 0.85; sRANKL 0.05 vs 0.03, P = 0.31; PRDX1 6.27 vs 6.21, P = 0.95; CAVI 11.13 vs 9.69, P = 0.15; cfPWV 10.82 vs 10.2, P = 0.55), however none were statistically significant. Levels of PRDX1 were elevated acutely post-event before falling significantly (R = −0.475, P = 0.002), while hsCRP and EPO continued to be elevated at >10 days post- event. In addition, CAVI correlated closely with hsCRP (R = 0.28, P = 0.09) and EPO (R = 0.29, P = 0.08), but cfPWV was not closely related to any of the biomarkers. Conclusions: This preliminary data suggests that biomarkers, particularly EPO and hsCRP, are more closely related to CAVI than cfPWV. hsCRP was the most relevant as an independent predictive factor for further vascular events.
- Published
- 2017
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34. Erythropoietin Increases Myelination in Oligodendrocytes: Gene Expression Profiling Reveals Early Induction of Genes Involved in Lipid Transport and Metabolism
- Author
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Georgina Gyetvai, Trisha Hughes, Florence Wedmore, Cieron Roe, Lamia Heikal, Pietro Ghezzi, and Manuela Mengozzi
- Subjects
central glia-4 ,microarrays ,CD36 ,Pnlip ,IGF-1 ,tissue-protective cytokines ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Several studies have shown that erythropoietin (EPO) has neuroprotective or neuroreparative actions on diseases of the nervous system and that improves oligodendrocyte (OL) differentiation and myelination in vivo and in vitro. This study aims at investigating the early molecular mechanisms for the pro-myelinating action of EPO at the gene expression level. For this purpose, we used a differentiating OL precursor cell line, rat central glia-4 cells. Cells were differentiated or not, and then treated with EPO for 1 or 20 h. RNA was extracted and changes in the gene expression profile were assessed using microarray analysis. Experiments were performed in biological replicates of n = 4. Differentiation alone changed the expression of 11% of transcripts (2,663 out of 24,272), representing 2,436 genes, half of which were upregulated and half downregulated. At 20 h of treatment, EPO significantly affected the expression of 99 genes that were already regulated by differentiation and of 150 genes that were not influenced by differentiation alone. Analysis of the transcripts most upregulated by EPO identified several genes involved in lipid transport (e.g., Cd36) and lipid metabolism (Ppargc1a/Pgc1alpha, Lpin1, Pnlip, Lpin2, Ppard, Plin2) along with Igf1 and Igf2, growth factors known for their pro-myelinating action. All these genes were only induced by EPO and not by differentiation alone, except for Pnlip which was highly induced by differentiation and augmented by EPO. Results were validated by quantitative PCR. These findings suggest that EPO might increase remyelination by inducing insulin-like growth factors and increasing lipid metabolism.
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- 2017
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35. Glutathione Fine-Tunes the Innate Immune Response toward Antiviral Pathways in a Macrophage Cell Line Independently of Its Antioxidant Properties
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Marina Diotallevi, Paola Checconi, Anna Teresa Palamara, Ignacio Celestino, Lucia Coppo, Arne Holmgren, Kahina Abbas, Fabienne Peyrot, Manuela Mengozzi, and Pietro Ghezzi
- Subjects
inflammation ,innate immunity ,TLR4 ,macrophages ,glutathione ,redox regulation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Glutathione (GSH), a major cellular antioxidant, is considered an inhibitor of the inflammatory response involving reactive oxygen species (ROS). However, evidence is largely based on experiments with exogenously added antioxidants/reducing agents or pro-oxidants. We show that depleting macrophages of 99% of GSH does not exacerbate the inflammatory gene expression profile in the RAW264 macrophage cell line or increase expression of inflammatory cytokines in response to the toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS); only two small patterns of LPS-induced genes were sensitive to GSH depletion. One group, mapping to innate immunity and antiviral responses (Oas2, Oas3, Mx2, Irf7, Irf9, STAT1, il1b), required GSH for optimal induction. Consequently, GSH depletion prevented the LPS-induced activation of antiviral response and its inhibition of influenza virus infection. LPS induction of a second group of genes (Prdx1, Srxn1, Hmox1, GSH synthase, cysteine transporters), mapping to nrf2 and the oxidative stress response, was increased by GSH depletion. We conclude that the main function of endogenous GSH is not to limit inflammation but to fine-tune the innate immune response to infection.
- Published
- 2017
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36. Online Information on Antioxidants: Information Quality Indicators, Commercial Interests, and Ranking by Google
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Pietro Ghezzi, Romaan Aslam, and Daniel Gibbons
- Subjects
Internet ,information quality ,Google ,websites ,antioxidants ,supplements ,Public aspects of medicine ,RA1-1270 - Abstract
The idea that antioxidant supplements can prevent or cure many diseases is extremely popular. To study the public understanding of antioxidants on the Web, we searched the term “antioxidants” in http://Google.com and analyzed 200 websites in terms of typology (news, commercial, professional, health portal, no-profit or government organization, scientific journals), disease or biological process mentioned (aging, immunity, neurological disease, diabetes, arthritis, etc.), and stance toward antioxidants, whether neutral, positive, or negative. Commercial and news websites were prevalent (over half of the total) but not in the top 10 returned by Google, where the most frequent were health portals, government, and professional websites. Among the diseases mentioned, cancer was the first, followed by vascular and eye diseases. A negative stance toward supplements was prevalent in the whole search, and this was even more evident for cancer. Information on aging or immunity had the largest proportion of pro-supplement and commercial websites. This study shows that some diseases are highly associated with antioxidants on the Internet and that information on antioxidants in aging and immunity is more likely to describe the positive effects of antioxidant supplements.
- Published
- 2017
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37. Erythropoietin (EPO) Increases Myelin Gene Expression in CG4 Oligodendrocyte Cells through the Classical EPO Receptor
- Author
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Ilaria Cervellini, Alexander Annenkov, Thomas Brenton, Yuti Chernajovsky, Pietro Ghezzi, and Manuela Mengozzi
- Subjects
Myelin Gene ,Medulla ,Early Growth Response Gene ,Myelin Oligodendrocyte Glycoprotein (MOG) ,Myelin Basic Protein (MBP) ,Therapeutics. Pharmacology ,RM1-950 ,Biochemistry ,QD415-436 - Abstract
Abstract Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in nonhematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP)). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by Western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects.
- Published
- 2013
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38. Is erythropoietin a worthy candidate for traumatic brain injury or are we heading the wrong way? [version 1; referees: 2 approved]
- Author
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Giovanni Grasso, Concetta Alafaci, and Pietro Ghezzi
- Subjects
Molecular Pharmacology ,Neuropharmacology & Psychopharmacology ,Medicine ,Science - Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability in the modern society. Although primary prevention is the only strategy that can counteract the primary brain damage, numerous preclinical studies have been accumulated in order to find therapeutic strategies against the secondary damage. In this scenario erythropoietin (EPO) has been shown to be a promising candidate as neuroprotective agent. A recent clinical trial, however, has shown that EPO has not an overall effect on outcomes following TBI thus renewing old concerns. However, the results of a prespecified sensitivity analysis indicate that the effect of EPO on mortality remains still unclear. In the light of these observations, further investigations are needed to resolve doubts on EPO effectiveness in order to provide a more solid base for tailoring conclusive clinical trials.
- Published
- 2016
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39. Role of glutathione in immunity and inflammation in the lung
- Author
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Pietro Ghezzi
- Subjects
Medicine (General) ,R5-920 - Abstract
Pietro GhezziBrighton and Sussex Medical School, Trafford Centre, Falmer, Brighton, UKAbstract: Reactive oxygen species and thiol antioxidants, including glutathione (GSH), regulate innate immunity at various levels. This review outlines the redox-sensitive steps of the cellular mechanisms implicated in inflammation and host defense against infection, and describes how GSH is not only important as an antioxidant but also as a signaling molecule. There is an extensive literature of the role of GSH in immunity. Most reviews are biased by an oversimplified picture where “bad” free radicals cause all sorts of diseases and “good” antioxidants protect from them and prevent oxidative stress. While this may be the case in certain fields (eg, toxicology), the role of thiols (the topic of this review) in immunity certainly requires wearing scientist’s goggles and being prepared to accept a more complex picture. This review aims at describing the role of GSH in the lung in the context of immunity and inflammation. The first part summarizes the history and basic concepts of this picture. The second part focuses on GSH metabolism/levels in pathology, the third on the role of GSH in innate immunity and inflammation, and the fourth gives 4 examples describing the importance of GSH in the response to infections.Keywords: antioxidants, oxidative stress, sepsis, infection, cysteine
- Published
- 2011
40. Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress.
- Author
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Paola Checconi, Sonia Salzano, Lucas Bowler, Lisa Mullen, Manuela Mengozzi, Eva-Maria Hanschmann, Christopher Horst Lillig, Rossella Sgarbanti, Simona Panella, Lucia Nencioni, Anna Teresa Palamara, and Pietro Ghezzi
- Subjects
Medicine ,Science - Abstract
Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions.
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- 2015
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41. Glucocorticoids as cytokine inhibitors: role in neuroendocrine control and therapy of inflammatory diseases
- Author
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Giamila Fantuzzi and Pietro Ghezzi
- Subjects
Pathology ,RB1-214 - Abstract
Glucocorticoids are potent inhibitors of inflammation and endotoxic shock. This probably occurs through an inhibition of the synthesis of pro-inflammatory cytokines as well as of many of their toxic activities. Therefore, endogenous glucocorticoids (GC) might represent a major mechanism in the control of cytokine mediated pathologies. GC inhibit the synthesis of cytokines in various experimental models. Adrenalectomy or GC antagonists potentiate TNF, IL-1 and IL-6 production in LPS treated mice. GC inhibit the formation of arachidonic acid metabolites and the induction of NO synthase. They also inhibit various activities of cytokines including toxicity, haemodynamic shock and fever. Adrenalectomy sensitizes to the toxic effects of LPS, TNF and IL-1. On the other hand, GC potentiate the synthesis of several cytokine induced APP by the liver. Since many of these proteins have anti-toxic activities (antioxidant, antiprotease etc.) or bind cytokines, this might well represent a GC mediated protective feedback mechanism involving the liver. Not only do GC inhibit cytokines, but in vivo LPS and various cytokines (TNF, IL-1, IL-6) increase blood GC levels through a central mechanism involving the activation of the HPA. Thus, this neuroendocrine response to cytokines constitutes an important immunoregulatory feedback involving the brain.
- Published
- 1993
- Full Text
- View/download PDF
42. Using Machine Learning for Automatic Identification of Evidence-Based Health Information on the Web.
- Author
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Majed M. Al-Jefri, Roger Evans, Pietro Ghezzi, and Gulden Uchyigit
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- 2017
- Full Text
- View/download PDF
43. Online information on medical cannabis may rise unrealistic expectations and downplay potential side effects.
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Arthur Cassa Macedo, André Oliveira Vilela de Faria, Isabella Harb Bizzi, Fabrício A. Moreira, Alessandro Colasanti, and Pietro Ghezzi
- Published
- 2020
44. Online information of vaccines: information quality is an ethical responsibility of search engines.
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Pietro Ghezzi, Peter G. Bannister, Gonzalo Casino, Alessia Catalani, Michel Goldman, Jessica Morley, Marie Neunez, Andreu Prados, Mariarosaria Taddeo, Tania Vanzolini, and Luciano Floridi
- Published
- 2019
45. Reporting on scientific studies in newspaper articles on COVID-19 in Italy and the US: missing citations and information bubbles
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Francesca Palatta, Arthur Cassa Macedo, Flavia Marcacci, Alessandro Martinisi, Daniella de Freitas Pereira Angelo Durço, Roberto Calheiros Barros Neto, and Pietro Ghezzi
- Abstract
Newspapers are a major source of health information, including on COVID-19. Many news articles are based on press releases describing research published in scientific journals. We studied a sample of articles in US and Italian newspapers for their mention of non-pharmacological interventions (face masks and lockdown) and pharmacological ones, both effective and ineffective (convalescent plasma, hydroxychloroquine, ivermectin, vaccines and vitamin D), and whether these were mentioned in a favorable or unfavorable way. We checked for the presence or absence of explicit mentions or links of the primary source of scientific information. Finally, we analyzed whether there was a trend to form “information bubbles” where some opinions around different treatments cluster together.Of 480,819 news in the USA and 767,172 in Italy, vaccines, face masks and lockdown were the most mentioned interventions. Of the pharmacological interventions other than vaccines, ivermectin and hydroxychloroquine were more frequently mentioned in the USA than in Italy (5- and 6-fold, respectively) although, when analyzing a sample of 210 news returned from a search on COVID-19 mentioning a research publication, articles from the USA were less favorable than those in Italy. We also found that the frequency of articles with a negative stance on vaccines was very small, indicating that the main newspapers do not contribute significantly to vaccine hesitancy. There was also evidence of information bubbles, where articles with a favorable or unfavorable view of a non-approved drug had the same stance on other non-approved treatments.Of the 210 news articles analyzed, half specifically mentioned a scientific publication. However, a link (or a complete citation) to the original source was provided in only 16% of Italian newspapers as opposed to 58% of those in the USA. The results highlight the fact that often news stories do not cite the scientific article they are reporting on, thus allowing the reader to verify the original source. This weakness in the citation behavior is particularly evident in Italian newspapers. This study suggests that linking to the original research article, rather than basing the news story on a press release, would improve the trustworthiness of the news and the critical thinking in the reader.
- Published
- 2023
46. Political polarization in the frequency British newspapers mention scientists with different views on COVID-19
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Pietro Ghezzi, Fabio Giglietto, and Alessandro Martinisi
- Abstract
Background. Measures against the COVID-19 pandemics have been subject of political polarization also in the United Kingdom. While this has been studied in the broader context of misinformation, the debate around non-pharmacological interventions (NPI) , the and the political implications of different views of their risks and benefits, has not been taken into account with sufficient depth Research question. Our research question was: Are politically-oriented UK newspapers more likely to promote a more, or less, precautionary views toward the use of NPIs?Methods. We used the Mediacloud database to search the names of scientists with different precautionary views (i.e.: signatories of the Great Barrington Declaration and of the John Snow Memorandum) and analyze the frequency with which they are mentioned in newspapers with different political orientation.Results. Scientists with more precautionary positions are more likely to be mentioned in left-leaning newspapers, whereas those with less precautionary views on right-leaning ones. The two groups segregated also in terms of co-authorship of academic papers.Conclusions. Scientists with different opinions in relation to NPIs are mentioned by UK newspapers in a way that is dependent on the political orientation of the newspaper.
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- 2023
47. Influenza virus replication is affected by glutaredoxin1-mediated protein deglutathionylation
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Paola Checconi, Cristiana Coni, Dolores Limongi, Sara Baldelli, Fabio Ciccarone, Marta De Angelis, Manuela Mengozzi, Pietro Ghezzi, Maria Rosa Ciriolo, Lucia Nencioni, and Anna Teresa Palamara
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deglutathionylation ,Virus Replication ,Biochemistry ,Glutathione ,influenza virus ,glutaredoxin1 ,Orthomyxoviridae Infections ,redox- regulation ,Influenza, Human ,Genetics ,Humans ,Settore BIO/10 ,Oxidoreductases ,Molecular Biology ,Oxidation-Reduction ,Protein Processing, Post-Translational ,glutathionylation ,Biotechnology ,glutathione - Abstract
Several redox modifications have been described during viral infection, including influenza virus infection, but little is known about glutathionylation and this respiratory virus. Glutathionylation is a reversible, post-translational modification, in which protein cysteine forms transient disulfides with glutathione (GSH), catalyzed by cellular oxidoreductases and in particular by glutaredoxin (Grx). We show here that (i) influenza virus infection induces protein glutathionylation, including that of viral proteins such as hemagglutinin (HA); (ii) Grx1-mediated deglutathionylation is important for the viral life cycle, as its inhibition, either with an inhibitor of its enzymatic activity or by siRNA, decreases viral replication. Overall these data contribute to the characterization of the complex picture of redox regulation of the influenza virus replication cycle and could help to identify new targets to control respiratory viral infection.
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- 2022
48. Special issue 'Extracellular Vesicles and Exosomes'
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Irving H. Zucker, Giovanni E. Mann, and Pietro Ghezzi
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Extracellular Vesicles ,Physiology (medical) ,Cell Communication ,Exosomes ,Biochemistry - Published
- 2022
49. On the Clinical Pharmacology of Reactive Oxygen Species
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Vincent Jaquet, Moises Di Sante, Ana I. Casas, Fabio Di Lisa, Alexandra Petraina, Nina Kaludercic, François Dufrasne, Antonio Cuadrado, Jalal Soubhye, Soni Deshwal, Cristian Nogales, Ana I. Rojo, Harald H.H.W. Schmidt, Hermann Mucke, Fiona Augsburger, Pietro Ghezzi, European Commission, European Research Council, and Maastricht University
- Subjects
0301 basic medicine ,XANTHINE-OXIDASE ,TRANSCRIPTION FACTOR NRF2 ,Disease ,Biology ,Antioxidants ,AMYOTROPHIC-LATERAL-SCLEROSIS ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,SERUM URIC-ACID ,SOLUBLE GUANYLATE-CYCLASE ,Animals ,Humans ,Pharmacological modulation ,Enzyme Inhibitors ,NITRIC-OXIDE SYNTHASE ,Chimie pharmaceutique ,VITAMIN-E ,Randomized Controlled Trials as Topic ,Pharmacology ,chemistry.chemical_classification ,Reactive oxygen species ,Clinical pharmacology ,Mechanism (biology) ,Drug discovery ,NADPH-OXIDASE ,MONOAMINE-OXIDASE ,3. Good health ,Chimie organique ,Oxidative Stress ,030104 developmental biology ,Cell metabolism ,Drug development ,chemistry ,CARDIOVASCULAR-DISEASE ,Molecular Medicine ,Reactive Oxygen Species ,Neuroscience ,Oxidation-Reduction ,030217 neurology & neurosurgery - Abstract
Rhian M. Touyz, Associate Editor, Reactive oxygen species (ROS) have been correlated with almost every human disease. Yet clinical exploitation of these hypotheses by pharmacological modulation of ROS has been scarce to nonexistent. Are ROS, thus, irrelevant for disease? No. One key misconception in the ROS field has been its consideration as a rather detrimental metabolic by-product of cell metabolism, and thus, any approach eliminating ROS to a certain tolerable level would be beneficial. We now know, instead, that ROS at every concentration, low or high, can serve many essential signaling and metabolic functions. This likely explains why systemic, nonspecific antioxidants have failed in the clinic, often with neutral and sometimes even detrimental outcomes. Recently, drug development has focused, instead, on identifying and selectively modulating ROS enzymatic sources that in a given constellation cause disease while leaving ROS physiologic signaling and metabolic functions intact. As sources, the family of NADPH oxidases stands out as the only enzyme family solely dedicated to ROS formation. Selectively targeting disease-relevant ROS-related proteins is already quite advanced, as evidenced by several phase II/III clinical trials and the first drugs having passed registration. The ROS field is expanding by including target enzymes and maturing to resemble more and more modern, big data–enhanced drug discovery and development, including network pharmacology. By defining a disease based on a distinct mechanism, in this case ROS dysregulation, and not by a symptom or phenotype anymore, ROS pharmacology is leaping forward from a clinical underperformer to a proof of concept within the new era of mechanism-based precision medicine., This study was supported by the European Research Council Advanced Investigator Grant/RadMed [Grant 294683], Proof-of-Concept Grant/SAVEBRAIN [Grant 737586], and H2020 Project REPO-TRIAL [Grant 777111] (to H.H.H.W.S.) and short-term scientific missions by the COST Actions EU-ROS and Open-MultiMed, and Kootstra Talented Fellowship (Maastricht University) (to A.I.C.).
- Published
- 2020
50. How the redox state regulates immunity
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Ben M. Alberts, Eva-Maria Hanschmann, Pietro Ghezzi, Lisa Mullen, and Manuela Mengozzi
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0301 basic medicine ,Oxidative phosphorylation ,medicine.disease_cause ,Biochemistry ,Redox ,Antioxidants ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunity ,Oxidoreductase ,Physiology (medical) ,medicine ,Cell damage ,chemistry.chemical_classification ,Reactive oxygen species ,Chemistry ,medicine.disease ,Cell biology ,Oxidative Stress ,030104 developmental biology ,Reactive Oxygen Species ,Oxidation-Reduction ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
Oxidative stress is defined as an imbalance between the levels of reactive oxygen species (ROS) and antioxidant defences. The view of oxidative stress as a cause of cell damage has evolved over the past few decades to a much more nuanced view of the role of oxidative changes in cell physiology. This is no more evident than in the field of immunity, where oxidative changes are now known to regulate many aspects of the immune response, and inflammatory pathways in particular. Our understanding of redox regulation of immunity now encompasses not only increases in reactive oxygen and nitrogen species, but also changes in the activities of oxidoreductase enzymes. These enzymes are important regulators of immune pathways both via changes in their redox activity, but also via other more recently identified cytokine-like functions. The emerging picture of redox regulation of immune pathways is one of increasing complexity and while therapeutic targeting of the redox environment to treat inflammatory disease is a possibility, any such strategy is likely to be more nuanced than simply inhibiting ROS production.
- Published
- 2020
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