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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 availability In an RCT, the status quo option in the notices influenced the rate of vaccine acceptance Nudging via pre-scheduled appointments encouraged vaccine uptake more than invitations to schedule did Switching the default option yielded a 32% relative increase (13.1% vs. 9.9%) in vaccination

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 aged 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.

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.

“Talk to the mothers of ill children, look at the suffering in their faces, there are very many cases that science ignores”. When you hear words like that, you had better start to worry; they are typical of those who, having recourse to the instrumental use of the emotions and supposed limits of the scientific method, advocate alternative therapeutic treatments to traditional medicine. Concern ought to start from the observation that these treatments are ineffective because something like “alternative medicine”, as opposed to “traditional medicine”, does not exist. Rather, medicine exists, with its data, its evidence, standard protocols and its rules of validation for drugs and therapies which even includes the use of experimental protocols for innovative therapies, the efficacy of which, partially shown, requires further proof. Outside this form of medicine there is no other medicine, simply there is nothing. This is why the expression “alternative treatments” is used, to clarify the fact that they have nothing to do with confirmed or experimental clinical therapies. The advocates of alternative treatments, in general, refuse these arguments, accusing doctors and scientists of being without a “mental openness” but this is another false argument: mental openness consists not of accepting opinions only because they are alternative to consolidated theories but remaining open to all the hypotheses or criticisms possible, on condition that they are based on data that can be proven. Mental openness is measured on facts, never on personal opinions—otherwise the risk is that of returning to magic or to witchcraft. Let’s look at the reasons why.

When a mother gives birth to a child naturally, in addition to life and love, she gives her baby a third gift which is often ignored: immunity. When the baby passes through the vaginal canal, it comes into contact with a series of “good” bacteria that offer it the first form of adaptation to the surrounding environment. Selected by the adaptive dynamics that are established between the mother and her ecological niche—her relationship with the environment, food, infectious agents and various allergens—they colonize the intestinal tract of the baby, who will inherit a strain of bacteria that are already well adapted to the environment where it will live. Made up of 100 trillion cells with a gene pool that is 100 times greater than the human one, this set of bacteria, known as the intestinal microbiome (the bacterial flora)—today considered like a real organ—has essential functions for human health, such as exploiting the energy of components that are difficult to assimilate, producing useful vitamins, keeping the immune system efficient and above all, competing with pathogenic bacteria and defending us from the aggression of microorganisms. Recent studies have shown that children who are born by caesarean section develop in the first years of life, and often later as well, some complications linked to the malfunctioning of their immune system, not only because they do not have the beneficial maternal “contagion” of useful bacteria but also because they can be damaged by infections due to the pathogenic bacteria present on the skin and in the hospital environment (Dominguez-Bello et al. 2010). In particular, babies born by caesarean section have a greater rate of asthma, allergic reactions, anaphylactic shock (atopic syndromes) and colitic disorders (Gronlund et al. 1999; Salminen et al. 2004; Negele et al. 2004; Debley et al. 2005; Biasucci et al. 2008; Neu and Rushing 2011).

Data, harsh data, are the only thing that count, we could say, paraphrasing a famous quotation from Stendhal’s The Red and the Black about the truth. At a time like the present, when we are submerged by information by media, it is not at all easy to find our way around to distinguish between what is true and what is false, in the sense of reported untruthfully or partially, or even fictive, in the sense of fake or fabricated. For my generation, which saw it come into being, the Internet has been and is a marvellous opportunity of cultural growth. Its strength lies in the freedom of the web, but so does its weakness. Alongside books and articles written by the most authoritative experts on every possible subject of human knowledge, there are texts that are cobbled together, manipulated or invented. The historian Carlo Ginzburg said this admirably in his lectio magistralis when he received the prestigious Balzan Prize (several of its winners have also received a Nobel Prize) in September 2011: Some have said that the Internet is an instrument of democracy. Taken literally, this statement is false. We have to add: it is an instrument of potential democracy. The motto of the Internet can be summarized in the words, paradoxical and politically incorrect, pronounced by Jesus: “Whoever has will be given more” (Matthew, XIII, 12). To navigate in the Internet, to distinguish the pearl from the sow’s ear, you already have to have had access to culture—an access which normally (and I speak from personal experience) is associated with social privilege. The Internet, which potentially could be an instrument that could attenuate cultural inequalities, in the immediate, exasperates them. Schools need the Internet, of course, but the Internet, to be used according to its potential (let’s say realistically one-millionth of its capacity), needs state schools that really teach.

Introduzione al Volume dedicato a Giuseppe Levi

The dangerous decline in vaccinations in many developed countries is at the heart of a lively debate that confirms how important the subject is today. Vaccinations are among mankind's most important scientific discoveries, yet they continue to be viewed with suspicion by part of the public - the victims of disinformation campaigns, instrumentalization and unfounded fears. There is, however, also an evolutionary explanation for these irrational beliefs, and countering the growing social opposition will be extremely difficult without grasping it. This book, which sheds new light on the safety and importance of vaccinations, is intended both for parents and those readers who want to understand the role of vaccinations in contemporary society, where the ease of access to knowledge is both a great opportunity and a great responsibility. The chapters follow a historical progression and conclude with a discussion of the most recent cognitive theories on how to overcome this opposition to vaccinations.

The story of the anti-vaccination movements, which have opposed vaccinations for health, religious and political reasons, is a story that is as old as the very practice of inoculating smallpox (Moulin 1996). In this long story, however, there has not been a single case where the movements have raised fears that the scientific community has deemed as having any grounds. However, they have at times reached results both in a legal context, obtaining in some cases exemption from compulsory vaccinations, and in the context of the pharmaceutical production. In one case, they succeeded having a preservative, unjustly deemed toxic, eliminated. Similar results, as will be seen, represent an apparent victory because they have not given any effective advantage to the anti-vaccination movements and, most importantly, at times they have even decreased herd immunity by causing new outbreaks of epidemics.

Three students who were subsequently awarded the Nobel Prize received part of their training in the Turin laboratory of the anatomist Giuseppe Levi (1872 - 1965): Salvador E. Luria for research on bacterial genetics (1969), Renato Dulbecco on oncogenic viruses (1975) and Rita Levi Montalcini for the discovery of the nerve growth factor (1986). It is a rare case in the history of science, especially considering the different paths that his three pupils took in the US after their common internship in Levi's laboratory which focused on the microanatomy of the nervous system. Trying to reconstruct the reasons for these professional successes, in their autobiographies, all three students recognized the great merits of their master's methodology (dedication and rigor in the job, the setting up and publication of the experiment, strictness and encouragement in the evaluations), while identifying the move to US labs as the decisive factor in their careers (research policy, meritocracy and substantial funding). In this contribution, I will attempt to trace the paths that made it possible for three students from an Italian school based on histology and microscopic anatomy according to the German tradition to become three Nobel laureates in various disciplines based on a molecular approach. Understanding how this 'metamorphosis' occurred means reconstructing how individual micro-histories, coming from a local scientific and methodological context -laboratory techniques, religious backgrounds, fortuitous choices, friendships and academic relations-, merged with macro-histories involving national politics, the Second World War, and institutional and disciplinary divisions.

The history of anti-vaccination movements is long and instructive. We can trace its beginnings back to late eighteenth century England and the practice of vaccinating against smallpox. From a historical point of view, we cannot say that opposition to vaccinations is anything new; what is new today is the increasingly large number of people involved and their social status. In addition, for the first time, we are seeing a decline in the vaccinal coverage of the population after two centuries of slow but inevitable advances: we are consequently seeing something very different from the opposition to vaccination in the past by some marginal groups.

Italian-born American physician Salvador E. Luria (1912–1991) was one of the founding fathers of bacterial genetics and molecular biology. Trained at the laboratory of the distinguished histologist Giuseppe Levi at the University of Turin and then in Rome with the school of physics Enrico Fermi, Luria was forced by the racial laws to emigrate to the United States. In 1943, together with the emigre German physicist Max Delbruck, he elaborated the ‘fluctuation test’ showing that the adaptive mechanisms of bacteria to virus (bacteriophages) attacks were attributable to the Darwinian principle of natural selection. For these pioneering research, and for founding the ‘phage group’, a sort of Mecca of the first molecular biologists, he obtained in 1969 the Nobel Prize for medicine. Politically engaged, Luria conduced in open contrast with American governments various battles for civil rights and pacifism. Keywords: bacterial genetics; phage group; Cold Spring Harbour Laboratory; molecular biology

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.

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. © 2014 Grignolio, Mishto, Faria, Garagnani, Franceschi and Tieri.

Stem cell tourism is a term recently coined to describe a growing practice among patients to pay large sums of money to private clinics for often unproven stem cell therapies. Patients can be desperate because conventional medicine has failed to provide a solution for their particular condition. For diseases affecting children, emotions may run particularly high: the children themselves cannot make properly informed decisions, so parents face the additional conflict of wanting the best for them while, at the same time, having to protect them from undue risk. Advertisements for these clinics, often outside the patient’s own country, claim that stem cell treatment can benefit or cure complaints ranging from diabetes, stroke, paralysis caused by spinal cord injury, cerebral palsy, and Lou Gehrig’s disease (ALS), to wrinkles in skin and age-related hair loss in men.

The fact that people age and die has always stimulated extensive philosophical and medical investigations in all societies. The early theories of ageing that arose in ancient Greece and revived in the Middle Age saw old age as a consequence of the gradual consumption of the innate heat with the inevitable loss of body moisture, according to Hippocrates’ system of four-humours (fifth century BC). The idea that senescence was itself an illness, the image of the aged body as a lamp in which life-fuel has run out, the character alterations of elders, the attempt to prolong life through specific diet or by substituting damaged body parts were the main themes around which research into ageing and senescence revolved from the Renaissance to the eighteenth century. The fresh tools provided by evolutionary theory and molecular biology have opened new vistas, sometimes retrieving old conceptions, of the intimate mechanisms underlying the recent prolongation of life expectancy. Key Concepts: Early speculations on ageing were focussed on the bodily humoural imbalance and on the gradual loss of inner heat. Rejuvenating or stopping the ageing process was a major concerns of Medieval and Renaissance medicine. Prolonging human lifespan through specific dietetic regimens was a long running theme in the history of gerontology. Evolutionary approaches and molecular disciplines gave a new impetus to the researches into ageing. No more considered itself a disease, senescence is nowadays sees as a successful form of remodelling and adaptation to a lifelong series stressors. In the past decades, ageing researches have concentrated their efforts in four major directions: cellular theories, immune-metabolic models, evolutionary explanations and molecular biology-based approaches. Keywords: Ageing; senescence; immortality; longevity; gerontology; geriatrics; history of medicine; theories of ageing; evolutionary theories

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.

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.