Use of immunology in news and YouTube videos in the context of COVID-19: politicisation and information bubbles.

Background: The COVID-19 pandemic propelled immunology into global news and social media, resulting in the potential for misinterpreting and misusing complex scientific concepts. Objective: To 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. Methods: In 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. Results: Vaccine-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. Conclusion: There 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.

Redox regulation of defense against bacterial and viral pathogens.

There is considerable interest in the role of oxygen-derived oxidants (often termed generically reactive oxygen species), and the potential effect of exogenous antioxidants, in the pathogenesis of infectious disease. Most of the published research focuses on the inflammatory response and the concept that oxidants are pro-inflammatory and antioxidants are anti-inflammatory. The present review discusses the evidence that both oxidants and thiol antioxidants are important in the various processes of innate and adaptive immunity, focusing on the function of the immune system in the defense against pathogens, rather than its pathogenic role in inflammatory and autoimmune disease.

Perspective: Daniela Novick, cytokines and their receptors.

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.

Influenza virus replication is affected by glutaredoxin1-mediated protein deglutathionylation.

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.

FRailty and Arterial stiffness - the role of oXidative stress and Inflammation (FRAXI study).

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.

Online information on medical cannabis is not always aligned with scientific evidence and may raise unrealistic expectations.

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.

Mitochondrial ROS, ER Stress, and Nrf2 Crosstalk in the Regulation of Mitochondrial Apoptosis Induced by Arsenite.

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.

The effect of radiofrequency electromagnetic fields (RF-EMF) on biomarkers of oxidative stress in vivo and in vitro: A protocol for a systematic review.

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.

Online information on face masks: analysis of websites in Italian and English returned by different search engines.

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.

Redox regulation of immunity and the role of small molecular weight thiols.

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.

Release of redox enzymes and micro-RNAs in extracellular vesicles, during infection and inflammation.

Many studies reported that redox enzymes, particularly thioredoxin and peroxiredoxin, can be released by cells and act as soluble mediators in immunity. Recently, it became clear that peroxiredoxins can be secreted via the exosome-release route, yet it remains unclear how this exactly happens and why. This review will first introduce briefly the possible redox states of protein cysteines and the role of redox enzymes in their regulation. We will then discuss the studies on the extracellular forms of some of these enzymes, their association with exosomes/extracellular vesicles and with exosome micro-RNAs (miRNAs)/mRNAs involved in oxidative processes, relevant in infection and inflammation.

Demystifying Oxidative Stress.

The hypothesis that reactive oxygen species (ROS) can be not just associated with but causally implicated in disease was first made in 1956, but so far, the oxidative stress theory of disease has not led to major therapeutic breakthrough, and the use of antioxidant is now confined to the field of complementary medicine. This chapter reviews the lack of high-level clinical evidence for the effectiveness of antioxidants in preventing disease and the epistemological problems of the oxidative stress theory of disease. We conclude on possible ways forward to test this hypothesis with approaches that take into account personalized medicine. The previous oxidative stress model has helped neither to diagnose nor to treat possibly ROS-related or ROS-dependent diseases. The redox balance concept that low ROS levels are beneficial or tolerable and high levels are disease triggers and best reduced is apparently wrong. Physiological ROS signalling may become dysfunctional or a disease trigger by at least five mechanisms: a physiological source may appear at an unphysiological site, a physiological source may be underactivated (less common) or overactivated (more common), a new source may appear, a physiological source may be overactivated or underactivated, and a toxifying enzyme may convert an ROS signal molecule into a more reactive molecule. The latter three mechanisms may reach a physiological or nonphysiological target. All of these dysregulations may be the direct and essential cause of a disease (rarely the case) or just a secondary epiphenomenon, which will disappear once the non-ROS-related cause of the disease is cured (much more common). Importantly, these mechanisms are the same for almost every signalling system. Causal target validation (sources, toxifiers and targets) is essential in order to identify effective drugs and therapies for ROSopathies.

On the Clinical Pharmacology of Reactive Oxygen Species.

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. SIGNIFICANCE STATEMENT: Despite being correlated to almost every human disease, nearly no ROS modulator has been translated to the clinics yet. Here, we move far beyond the old-fashioned misconception of ROS as detrimental metabolic by-products and suggest 1) novel pharmacological targeting focused on selective modulation of ROS enzymatic sources, 2) mechanism-based redefinition of diseases, and 3) network pharmacology within the ROS field, altogether toward the new era of ROS pharmacology in precision medicine.

C-Reactive Protein Predicts Further Ischemic Events in Patients With Transient Ischemic Attack or Lacunar Stroke.

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.

Online Information of Vaccines: Information Quality, Not Only Privacy, Is an Ethical Responsibility of Search Engines.

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.