Polysulfide nanoparticles inhibit fibroblast-to-myofibroblast transition via extracellular ROS scavenging and have potential anti-fibrotic properties.

This paper is about the effects of reactive oxygen species (ROS) - and of their nanoparticle-mediated extracellular removal - in the TGF-ß1-induced differentiation of fibroblasts (human dermal fibroblasts - HDFa) to more contractile myofibroblasts, and in the maintenance of this phenotype. Here, poly(propylene sulfide) (PPS) nanoparticles have been employed on 2D and 3D in vitro models, showing extremely low toxicity and undergoing negligible internalization, thereby ensuring an extracellular-only action. Firstly, PPS nanoparticles abrogated ROS-mediated downstream molecular events such as glutathione oxidation, NF-κB activation, and heme oxidase-1 (HMOX) overexpression. Secondly, PPS nanoparticles were also capable to inhibit, prevent and reverse the TGF-ß1-induced upregulation of key biomechanical elements, such as ED-a fibronectin (EF-A FN) and alpha-smooth muscle actin (α-SMA), respectively markers of protomyofibroblastic and of myofibroblastic differentiation. We also confirmed that ROS alone are ineffective promoters of the myofibroblastic transition, although their presence contributes to its stabilization. Finally, the particles also countered TGF-ß1-induced matrix- and tissue-level phenomena, e.g., the upregulation of collagen type 1, the development of aberrant collagen type 1/3 ratios and the contracture of HDFa 3D-seeded fibrin constructs. In short, experimental data at molecular, cellular and tissue levels show a significant potential in the use of PPS nanoparticles as anti-fibrotic agents.

Scientific Misinformation and Mistrust of COVID-19 Preventive Measures among the UK Population: A Pilot Study.

The popularisation of complex biomedical concepts brought about by COVID-19 has led to the rapid proliferation and diffusion of scientific misinformation, particularly among individuals with inadequate levels of scientific and digital literacy. A cross-sectional online survey of a UK population sample was conducted to address three key aims: to verify whether there is a correlation between participants' belief in false information around COVID-19 and adherence to preventive measures; to investigate whether participants' scientific misinformation and preventive behaviour are associated with their demographic characteristics; and to evaluate whether participants' scientific misinformation and preventive behaviour can predict their likelihood of having contracted COVID-19. Non-parametric data analysis highlighted a strong negative correlation between participants' belief in misinformation and their trust in preventive measures. Both variables were significantly associated with participants' education levels, but not with their religious beliefs. Remarkably, neither science misinformation levels nor the trust in preventive measures were statistically associated with the likelihood of having contracted COVID-19. Taken together, these findings reinforce the urgency of ensuring that the population is equipped with adequate scientific literacy to enable them to evaluate the reliability of scientific information and recognise the importance of individual preventive behaviours to minimise community spread of infectious diseases.

Real-life research projects improve student engagement and provide reliable data for academics.

Student engagement can have a positive influence on student success. Many methods exist for fostering engagement but tend to be generic and require tailoring to specific contexts, subjects, and students. In the case of undergraduate science students, practical classes are a popular tool for increasing engagement. However, despite strong potential for improvement via links with "real life" research projects (RLRPs), few academic staff incorporate research participation with teaching activities. This is potentially due to poor time availability and low opinions of students' ability to collect reliable data. This study aims to examine whether involvement with RLRPs can generate reliable scientific data and also act as a motivational tool for engaging tertiary science students. A preexisting core activity for first-year biology and marine biology students was modified to include a short RLRP component. Student-based data collection and a questionnaire about experiences were used to examine the reliability of student-collected data and student perceptions of RLRPs. Results indicated that error rate in student-collected data was minimal. Irrespective of participating in a "normal" practical class or a class with a RLRP component, students collected equally accurate data. However, when the topic aligned specifically with their degree subject, student accuracy was higher. All students surveyed reported high motivation with the idea of RLRP participation, placing high importance on this from an educational and employability perspective. Yet, students were not confident about participating in RLRPs until they had engaged with one, suggesting that introducing such projects into taught sessions early-on may encourage students to seek further opportunities in the future. In conclusion, incorporating RLRPs into the curriculum of undergraduate science courses has considerable potential benefits for both students and academic staff.

Is vaccine confidence an unexpected victim of the COVID-19 pandemic?

Vaccines are among the safest and most effective primary prevention measures. Thanks to the synergistic global efforts of research institutions, pharmaceutical companies and national health services, COVID-19 vaccination campaigns were successfully rolled out less than a year after the start of the pandemic. While the unprecedented speed of development and approval of COVID-19 vaccines has been applauded as a public health success story, it also spurred considerable controversy and hesitancy even amongst individuals that did not previously hold anti-vaccination stances. This study aimed to compare pre- and post-pandemic vaccine confidence trends in different demographic groups by analysing the outcomes of two online surveys run respectively in November 2019 and January 2022 involving a total of 1009 participants. Non-parametric tests highlighted a statistically significant decline in vaccine confidence in the 2022 cohort compared to the 2019 cohort, with median Vaccine Confidence Score dropping from 22 to 20 and 23.8% of participants reporting that their confidence in vaccines had declined since the onset of the pandemic. While the majority of internal trends were comparable between the two surveys with regards to gender, graduate status and religious belief, vaccine confidence patterns showed considerable alterations with regards to age and ethnicity. Middle-aged participants were considerably more hesitant than younger groups in the 2019 cohort, however this was not the case in the 2022 survey. In both surveys White participants showed significantly higher vaccine confidence than those from Black backgrounds; in the 2022 cohort, unlike the pre-pandemic group, Asian participants showed significantly lower confidence than White ones. This study suggests that paradoxically, despite the success of COVID-19 vaccination campaigns, vaccine confidence has significantly declined since the onset of the pandemic; the comparison of a pre- and post-pandemic cohort sheds light on the differential effect that the pandemic had on vaccine confidence in different demographic groups.

Political views and science literacy as indicators of vaccine confidence and COVID-19 concern.

Introduction: The distrust, delay and refusal of vaccinations represent serious threats to global public health. As demonstrated by the dramatic worldwide impact of the COVID-19 pandemic, adequate vaccine coverage against infectious diseases is essential towards the preservation and function of virtually every aspect of our society. While the determinants of vaccine hesitancy and pandemic concern have been widely investigated, conflicting evidence exists with regards to their association with education levels and political views. Methods: This study aimed to investigate whether science literacy levels and standpoint on social and economic matters are associated with different levels of vaccine confidence and COVID-19 concern. An online survey was circulated amongst participants recruited via convenience sampling, and data were analysed using non-parametric statistical tests. Results: The survey (n = 389) highlighted that participants who studied Science at General Certificate of Secondary Education level have a lower vaccine confidence than those with both lower and higher levels of science education. Participants with neutral/centrist political views expressed lower confidence than those with a libertarian social stance or a left-wing economic stance. A higher concern with the COVID-19 pandemic was associated with lower levels of science education, libertarian social views, and left-wing economic views. Conclusions: The present study provides novel insight on the educational and political factors associated with vaccine hesitancy and pandemic concern within a British population sample.

The contracture-in-a-well. An in vitro model distinguishes bulk and interfacial processes of irreversible (fibrotic) cell-mediated contraction.

Tissue contractures are processes of cell-mediated contraction, irreversible in nature and typically associated with fibrotic phenomena. Contractures can be reproduced in vitro; here, we have used a medium-throughput model based on fibroblast-seeded fibrin (the 'contracture well'). Firstly, we show how profoundly these processes depend on the location of the contractile cells: when on top of the material, fibroblasts produce an interfacial contracture (analog to capsular contraction around an implant), which tries and bends the construct; when seeded inside the material, they initiate a bulk contracture (analogue to a wound bed closure) that shrinks it from within. Secondly, we demonstrate that the interfacial and bulk contractures are also mechanically and biologically different processes. Thirdly, we show the potentially predictive value of this model, since it not only recapitulates the effect of pro-fibrotic factors (TGF-ß1 for dermal (myo)fibroblasts), but can also indicate the fibrotic potential of a given cell population (here, dystrophic myoblasts more fibrotic than healthy or genetically corrected ones), which may have important implications in the identification of appropriate therapies.

Investigating the determinants of vaccine hesitancy within undergraduate students' social sphere.

Aims: Vaccine hesitancy is widely recognised as one of the most serious threats to current global health. While the causes underlying vaccine hesitancy have been extensively described and several mitigation strategies trialled amongst current and prospective parents, there is a relative scarcity of research investigating its extent and causative factors amongst university students, a critical demographic due to its temporal proximity to the average child-rearing age. The present study sought to address this literature gap by elucidating the social and demographic factors that might underpin vaccine hesitancy in university students. Subject and methods: An anonymous online survey was carried out to investigate the opinions and perspectives on the practice of vaccination within undergraduate students' social sphere. The statistical significance of the differences observed between groups of participants was analysed using non-parametric tests of variance. Results: Amongst the 739 volunteers who participated in the survey, vaccine confidence varied significantly (p < 0.001) with age, ethnicity and religion, and to a lesser (yet still statistically significant) extent (p < 0.05) with graduate status. No statistically significant differences were observed with regard to gender or number of children. Conclusions: By shedding new light on the factors underpinning vaccine hesitancy within undergraduate students' social network, the present study provides a stepping stone towards the development of targeted mitigation strategies.

Impact of the recreational use of virtual reality on physical and mental wellbeing during the Covid-19 lockdown.

The Covid-19 pandemic has brought about significant changes to most aspects of our lives. As a result of the quarantine enforced by governments and authorities worldwide, people had to suddenly adapt their daily routines, including work, study, diet, leisure and fitness activities to the new circumstances. A growing body of research indicates that the engagement with virtual reality (VR) activities can have a positive impact on users' mental and physical wellbeing. This study aims to evaluate the impact of VR activities on users under lockdown due to the Covid-19 pandemic. An online survey was carried out to investigate the recreational use of VR during the lockdown period and to gather users' opinions on its impact on their physical and mental health. Non-parametric tests were used to evaluate the statistical significance of the responses provided by the 646 participants. The results of the survey show that VR use has significantly increased during the lockdown period for most participants, who expressed overwhelmingly positive opinions on the impact of VR activities on their mental and physical wellbeing. Strikingly, self-reported intensity of physical activity was considerably more strenuous in VR users than in console users. Given the current uncertainty as to the duration and course of the pandemic, as well as the possibility of intermittent lockdown in the upcoming years, the outcomes of this study could have a significant impact towards the development and deployment of VR-based strategies aimed at helping the population cope with prolonged social distancing, with particular regards to vulnerable individuals.

Measles outbreaks in Italy: A paradigm of the re-emergence of vaccine-preventable diseases in developed countries.

Over the last decade, outbreaks of vaccine-preventable diseases have been reported in developed countries around the world. In particular, measles outbreaks have been ongoing in the European Union since 2017, with the majority of cases concentrated in Romania and Italy. Measles has been identified as a powerful indicator of the status of vaccination programs in a region, as outbreaks have been reported to quickly emerge as a result of underlying problems in the immunisation routine. This paper aims to report and critically comment on the factors underpinning the recent measles outbreaks in Italy, considering the psychological, cultural, social and political causes of vaccine hesitancy and refusal amongst the population. Data from government agencies including the Italian National Institute of Statistics (ISTAT) and the Italian National Institute of Health (ISS) are analysed to describe incidence and mortality trends from 1887 to the present day, including regional variations and the impact of measles vaccination coverage. The topic of compulsory vaccination is currently the object of heated debate in the Italian social and political panorama; this paper discusses the current state of the vaccination controversy in the Italian political discourse and its potential impact on immunisation policies and measles vaccine coverage amongst the population. A burgeoning body of evidence indicates that every effort should be made to bolster the existing legislation on mandatory vaccination through widespread health education campaigns aimed at improving scientific literacy amongst the Italian population with regards to the topic of immunisation.

Fibronectin localization and fibrillization are affected by the presence of serum in culture media.

In vitro models of fibrotic phenomena are often based on the fibroblast-myofibroblast transition as the contraction-triggering cellular event. There are, however, multiple sources of concern regarding the appropriateness of such models; a first and widely investigated issue is the often inappropriate nature of the interactions between mesenchymal cells and surrounding/underlying matrix/substrate. A second set of problems concerns the composition of the fluid phase, which includes both dispersed/dissolved paracrine messengers and matrix elements. In this study, we have focused on the effects that serum may generate. We have observed that A) serum causes high variability in the expression of typical markers of myofibroblast differentiation (ED-A fibronectin and α-Smooth Muscle Actin) upon treatment with TGF-ß1; this is probably due to intrinsic variability of cytokine concentrations in different batches of serum. B) the fibrillization of endogenous fibronectin is partially hampered and its localization changed from ventral (on the substrate) to dorsal (upper surface); the latter morphology appears to be largely overlooked in literature, even though it may have a significant role in terms of mechanotransductive signaling. This quite dramatic change possibly occurs as a result of competition with serum proteins, although our data seem to rule out a direct role of serum fibronectin.

Myofibroblast differentiation: main features, biomedical relevance, and the role of reactive oxygen species.

SIGNIFICANCE: Myofibroblasts are prototypical fibrotic cells, which are involved in a number of more or less pathological conditions, from foreign body reactions to scarring, from liver, kidney, or lung fibrosis to neoplastic phenomena. The differentiation of precursor cells (not only of fibroblastic nature) is characterized by a complex interplay between soluble factors (growth factors such as transforming growth factor ß1, reactive oxygen species [ROS]) and material properties (matrix stiffness). RECENT ADVANCES: The last 15 years have seen very significant advances in the identification of appropriate differentiation markers, in the understanding of the differentiation mechanism, and above all, the involvement of ROS as causative and persistence factors. CRITICAL ISSUES: The specific mechanisms of action of ROS remain largely unknown, although evidence suggests that both intracellular and extracellular phenomena play a role. FUTURE DIRECTIONS: Approaches based on antioxidant (ROS-scavenging) principles and on the potentiation of nitric oxide signaling hold much promise in view of a pharmacological therapy of fibrotic phenomena. However, how to make the active principles available at the target sites is yet a largely neglected issue.

Quantitative descriptors for the effect of nature/mechanical properties of solid substrates on fibroblast morphology.

PURPOSE: Cell shape is a powerful indicator of cell activity. This study aimed to validate the use of numeric descriptors for the assessment of the effect of substrate mechanical properties on the morphology of 2D cultured fibroblasts. METHODS: Two fibroblast cell types, the 3T3 murine cell line and primary Human Dermal Fibroblasts (HDF) were cultured on substrates (fibrin, silicone, Tissue Culture PolyStyrene) with modulus values spanning more than six orders of magnitude (<1kPa - > 1 GPa), using cell area, circularity, aspect ratio and solidity (ratio between actual and convex area) as morphologic descriptors of cell shape. In order to reduce differences in chemical composition, silicones and TCPS were pre-treated with fibrinogen. RESULTS: Cell area and solidity appeared to be the most sensitive indicators of the differential dependency of the cell morphology on the nature of the substrate. They highlighted complex behavior, where the increase in modulus did not correspond to clear trends in cell shape over the complete range of moduli investigated. CONCLUSIONS: The analysis of cell shape descriptors appears to indicate that chemical differences may overwhelm mechanical effects in 2D culture. These indications are partial and purely phenomenologic, but suggest that specific care should be paid to also consider the role of substrate chemistry in the analysis of the dependency of cell behavior on substrate mechanical properties.