Nudging COVID-19 Vaccine Uptake by Changing the Default: A Randomized Controlled Trial.

BACKGROUND: Although vaccination against SARS-CoV-2 is considered the central strategy against the pandemic, uptake lags behind target rates. METHOD: To explore whether this rate could be enhanced by a nudging strategy that exploits the status quo bias, we conducted a randomized controlled trial in northern Italy comparing vaccination acceptance among 2000 adults, ages 50 to 59 years, who were either invited to set an appointment (opt-in group) or assigned an individual appointment (opt-out group). RESULTS: Results indicate a difference of 3.2 percentage points, which represents a 32% relative increase in the vaccination rate for the opt-out group compared with the opt-in group. CONCLUSIONS: A significant portion of those who remain unvaccinated may not hold strong beliefs against vaccination but rather tend to inaction and may therefore be nudged toward vaccination with a reduction of action required. HIGHLIGHTS: Reluctant adults (50-59 years), who had not yet received vaccines against COVID-19, were sent letters announcing appointment availabilityIn an RCT, the status quo option in the notices influenced the rate of vaccine acceptanceNudging via pre-scheduled appointments encouraged vaccine uptake more than invitations to schedule didSwitching the default option yielded a 32% relative increase (13.1% vs. 9.9%) in vaccination.

The future for COVID-19 vaccines: public health assessment and perspectives based on scientific evidence.

The development and use of messenger RNA-based (mRNA) vaccines against the SARS-CoV-2 spike protein have proven to be highly effective against symptomatic COVID-19, especially for severe forms. Since the declaration of a public health emergency in early 2020, however, the SARS-CoV-2 virus has continuously evolved, giving rise to several variants that have caused and continue to cause concern in the scientific community. Currently, viruses circulating worldwide belong to the Omicron lineage, with several identified sub-variants. In response to virus mutation, mRNA vaccines have been adapted into bivalent vaccines containing two mRNAs: one encoding the original Wuhan SARS-CoV-2 spike protein and one encoding the BA.1 or BA.4-5 spike protein of the Omicron sub-variant. This strategy is based on the hypothesis that the immune system's response improves when variants are included in the vaccine, leading to an increase in the magnitude and diversity of both the humoral and cellular immune response. The evidence gathered to date confirms the use of bivalent vaccines as the optimal strategy. In the light of current knowledge, and in the awareness of the impossibility of making precise predictions on the evolution of the COVID-19 pandemic, as a group of experts we propose some considerations for the progressive evolution of vaccination against SARS-CoV-2 from pandemic to endemic vaccination.

Knowledge, attitudes and practices about vaccination in Trentino, Italy in 2019.

Introduction: Vaccination is among the most important areas of progress in the worldwide history of public health. However, a crescent wave of anti-vaccine groups has grown in Western countries, especially in Italy, in the last two decades. Our aim was to evaluate adult's hesitancy and knowledge about vaccines and related diseases in Trentino-Alto Adige -the Italian region with the lowest vaccination coverages. Methods: We administered self-answered structured questionnaires in three malls in the Trentino province in June 2019. We collected demographic data and information on knowledge about vaccines, infectious diseases and attitude in seeking health information. We utilized a descriptive and multivariate analysis to investigate factors associated with vaccine hesitancy. Results: We collected 567 questionnaires, 18% of the people interviewed were hesitant toward vaccination and 16% were against mandatory vaccination. In the multivariate analysis a poor level of information, being younger than 60 years and being against compulsory vaccination were associated with vaccine hesitancy. Regarding information about vaccines, 76.5% of the people relied on physicians, and/or 49% navigated the internet, while social media are used by 16% of the study population. Though 41.5% searched information on official sites, only 14% knew the website VaccinarSì and 4.7% had visited it. Discussion: Compared to a previous study conducted in all of Italy except Trentino Alto Adige, the level of vaccination hesitancy was higher. It is important to utilize health professionals, the internet and especially social media to spread scientific information about vaccination.

Potential predictors of type-2 diabetes risk: machine learning, synthetic data and wearable health devices.

BACKGROUND: The aim of a recent research project was the investigation of the mechanisms involved in the onset of type 2 diabetes in the absence of familiarity. This has led to the development of a computational model that recapitulates the aetiology of the disease and simulates the immunological and metabolic alterations linked to type-2 diabetes subjected to clinical, physiological, and behavioural features of prototypical human individuals. RESULTS: We analysed the time course of 46,170 virtual subjects, experiencing different lifestyle conditions. We then set up a statistical model able to recapitulate the simulated outcomes. CONCLUSIONS: The resulting machine learning model adequately predicts the synthetic dataset and can, therefore, be used as a computationally-cheaper version of the detailed mathematical model, ready to be implemented on mobile devices to allow self-assessment by informed and aware individuals. The computational model used to generate the dataset of this work is available as a web-service at the following address: http://kraken.iac.rm.cnr.it/T2DM .

The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates.

Geroscience, the new interdisciplinary field that aims to understand the relationship between aging and chronic age-related diseases (ARDs) and geriatric syndromes (GSs), is based on epidemiological evidence and experimental data that aging is the major risk factor for such pathologies and assumes that aging and ARDs/GSs share a common set of basic biological mechanisms. A consequence is that the primary target of medicine is to combat aging instead of any single ARD/GSs one by one, as favored by the fragmentation into hundreds of specialties and sub-specialties. If the same molecular and cellular mechanisms underpin both aging and ARDs/GSs, a major question emerges: which is the difference, if any, between aging and ARDs/GSs? The hypothesis that ARDs and GSs such as frailty can be conceptualized as accelerated aging will be discussed by analyzing in particular frailty, sarcopenia, chronic obstructive pulmonary disease, cancer, neurodegenerative diseases such as Alzheimer and Parkinson as well as Down syndrome as an example of progeroid syndrome. According to this integrated view, aging and ARDs/GSs become part of a continuum where precise boundaries do not exist and the two extremes are represented by centenarians, who largely avoided or postponed most ARDs/GSs and are characterized by decelerated aging, and patients who suffered one or more severe ARDs in their 60s, 70s, and 80s and show signs of accelerated aging, respectively. In between these two extremes, there is a continuum of intermediate trajectories representing a sort of gray area. Thus, clinically different, classical ARDs/GSs are, indeed, the result of peculiar combinations of alterations regarding the same, limited set of basic mechanisms shared with the aging process. Whether an individual will follow a trajectory of accelerated or decelerated aging will depend on his/her genetic background interacting lifelong with environmental and lifestyle factors. If ARDs and GSs are manifestations of accelerated aging, it is urgent to identify markers capable of distinguishing between biological and chronological age to identify subjects at higher risk of developing ARDs and GSs. To this aim, we propose the use of DNA methylation, N-glycans profiling, and gut microbiota composition to complement the available disease-specific markers.

The emerging role of ECM crosslinking in T cell mobility as a hallmark of immunosenescence in humans.

Immunosenescence is thought to result from cellular aging and to reflect exposure to environmental stressors and antigens, including cytomegalovirus (CMV). However, not all of the features of immunosenescence are consistent with this view, and this has led to the emergence of the sister theory of "inflammaging". The recently discovered diffuse tissue distribution of resident memory T cells (TRM) which don't recirculate, calls these theories into question. These cells account for most T cells residing in barrier epithelia which sit in and travel through the extracellular matrix (ECM). With almost all studies to date carried out on peripheral blood, the age-related changes of the ECM and their consequences for T cell mobility, which is crucial for the function of these cells, have been largely ignored. We propose an update of the theoretical framework of immunosenescence, based on a novel hypothesis: the increasing stiffness and cross-linking of the senescent ECM lead to a progressive immunodeficiency due to an age-related decrease in T cell mobility and eventually the death of these cells. A key element of this mechanism is the mechanical stress to which the cell cytoplasm and nucleus are subjected during passage through the ECM. This hypothesis is based on an "evo-devo" perspective bringing together some major characteristics of aging, to create a single interpretive framework for immunosenescence.

Towards a liquid self: how time, geography, and life experiences reshape the biological identity.

The conceptualization of immunological self is amongst the most important theories of modern biology, representing a sort of theoretical guideline for experimental immunologists, in order to understand how host constituents are ignored by the immune system (IS). A consistent advancement in this field has been represented by the danger/damage theory and its subsequent refinements, which at present represents the most comprehensive conceptualization of immunological self. Here, we present the new hypothesis of "liquid self," which integrates and extends the danger/damage theory. The main novelty of the liquid self hypothesis lies in the full integration of the immune response mechanisms into the host body's ecosystems, i.e., in adding the temporal, as well as the geographical/evolutionary and environmental, dimensions, which we suggested to call "immunological biography." Our hypothesis takes into account the important biological changes occurring with time (age) in the IS (including immunosenescence and inflammaging), as well as changes in the organismal context related to nutrition, lifestyle, and geography (populations). We argue that such temporal and geographical dimensions impinge upon, and continuously reshape, the antigenicity of physical entities (molecules, cells, bacteria, viruses), making them switching between "self" and "non-self" states in a dynamical, "liquid" fashion. Particular attention is devoted to oral tolerance and gut microbiota, as well as to a new potential source of unexpected self epitopes produced by proteasome splicing. Finally, our framework allows the set up of a variety of testable predictions, the most straightforward suggesting that the immune responses to defined molecules representing potentials antigens will be quantitatively and qualitatively quite different according to the immuno-biographical background of the host.

Network, degeneracy and bow tie. Integrating paradigms and architectures to grasp the complexity of the immune system.

Recently, the network paradigm, an application of graph theory to biology, has proven to be a powerful approach to gaining insights into biological complexity, and has catalyzed the advancement of systems biology. In this perspective and focusing on the immune system, we propose here a more comprehensive view to go beyond the concept of network. We start from the concept of degeneracy, one of the most prominent characteristic of biological complexity, defined as the ability of structurally different elements to perform the same function, and we show that degeneracy is highly intertwined with another recently-proposed organizational principle, i.e. 'bow tie architecture'. The simultaneous consideration of concepts such as degeneracy, bow tie architecture and network results in a powerful new interpretative tool that takes into account the constructive role of noise (stochastic fluctuations) and is able to grasp the major characteristics of biological complexity, i.e. the capacity to turn an apparently chaotic and highly dynamic set of signals into functional information.

[An illustrious unknown. Giuseppe Levi among science, anti-fascism and Nobel Prizes]. / Uno sconosciuto illustre: Giuseppe Levi tra scienza, antifascismo e Premi Nobel.

The anatomist Giuseppe Levi (1872-1965) is unanimously considered one of the major figures of Italian biomedical sciences in the 20th century. His fame, however, is mainly derived from having nurtured three Nobel Prize winners, namely Salvador E. Luria, Rita Levi Montalcini and Renato Dulbecco. In reappraising Levi's role in the development of Italian science and culture in general, this article aims at questioning both the narrowness of earlier accounts and a certain kind of genealogical approach to the history of scientific disciplines and academic schools. We will here consider Giuseppe Levi as an instance of two major cultural phenomena: the development of experimental biology in Italy and continental Europe and the anti-fascist socialist culture expressed by a part of the Italian intellectuals. In so doing, we will reassess the historical specificity of the scientific maturation of Levi's three famous students, on the one hand, while on the other we will consider in some depth the cultural and moral environment in which Levi thrived and his role as a moral example for his students. Such revision, we will argue, have a direct bearing on more general historiographical issues, namely, the need for a stronger contextualization of the birth and consolidation of research traditions, implying a rejection of simplistic genealogical reconstructions, and the role of academic schools and institutional settings in the definition of novel, multidisciplinary scientific approaches. Finally, the following will highlight the importance of a more careful outlook on the master-pupil relationship in academic context, addressing issues of both continuity and rupture. The article is subdivided in two main sections, the first devoted to Levi as a scientist, the second to his Anti-fascism.