Tuberculosis: a timeless challenge for medicine

History of Medicine is not a discipline destined to culturally enrich only those who work in the health sector. All historians know very well how some medical events have influenced the course of history. In particular, infectious diseases, being interconnected with political, social, economic and war issues, have an important historical significance.Microbial agents are invisible enemies ready to undermine mankind and to find prosperity in human misery.Tuberculosis, better than other, is well suited to study the epistemological path of medical thought, from its origins to the present day.From the Hippocratic and Galenic thought to the anatomo-clinical method, from the advent of microbiology to the antibiotic era up to the postantibiotic era, recognizing the timeless need to implement valid social policies and effective preventive medicine actions to achieve satisfactory results

COVID-19 and Spanish flu-18: review of medical and social parallelisms between two global pandemics

The intrusion of infectious diseases in everyday life forces humans to reassess their attitudes. Indeed, pandemics are able catalyze rapid transitions in scientific knowledge, politics, social behaviors, culture and arts. The current Coronavirus diesease-19 (COVID-19) outbreak has driven an unprecedented interest toward the influenza pandemic of 1918. The issue is whether history can predict our best preventive response and future scenarios. The aim of this review is to highlight the parallelism between the two pandemics. Starting from epidemiology and clinical features, but further focusing on social and cultural issues, it is possible to unreveal great similarities. Their outbreak pattern lead to hypothesize a similar duration and death burden in absence of effective vaccines or innovative treatments for COVID-19. Thus, then as now, preventive medicine represents the first and most effective tool to contain the course of the pandemic; being treatments available only supportive. Contemporary, both pandemics shared the same pattern of narration (e.g. scapegoating) and the same impact on minorities in high-income countries. Furthermore, visual art did not wait to respond with Graffiti art playing in 2020 the role that Expressionism movement had during the Spanish flu and photography capable to document both catastrophic scenarios. Thus, it is possible to find a lot of clinical and social similarities between the two pandemics. Nevertheless, if the Spanish flu was not unforseen, COVID-19 spillover was partially predictable and its global impact will not be overshadowed by a major crisis such as World War I

A role for startups in unleashing the disruptive power of social media

As social media attract increasing attention from executives and find varied applications in different industries, research on the subject has been investigating the antecedents, moderators, mediators and outcomes of social media adoption, as well as impacts on the organizational and individual level. However, relatively little attention has been paid to the discussion of the new sources of social media innovation-i.e., the upstream originators of social media solutions. Such innovations of a possibly disruptive nature often originate from startups, which can constitute a significant driver for social media development and can influence the adopting incumbents' behaviors. This study aims at shedding first light on social media-based solutions developed and delivered by startups. By surveying the Crunchbase database, we identified 724 funded social media startups, which were further classified into six categories, namely: (i) social network; (ii) social commerce; (iii) social recruitment; (iv) social management; (v) social loyalty and advocacy; (vi) contact management. Our findings show how the large majority of startups deliver social network solutions to incumbents, followed by social media management applications. The findings also shed light on emerging approaches to value generation and open innovation from social media related to and driven by startups

The avid eaters of lives. New and old infectious diseases in Italy at the time of World War 1: a historical overview of military medicine and public health

World War I bursted Italy from different perspectives. The one here described under an historical point of view reguards health of military and civil population, with a special focus on infective diseases. The 20th Century was the fuse of degeneration and eugenetics theories; which grew in the meliè of war and technological innovation. Indeed, war is interestingly depicted as an entity capable of blooming the differences between those who wore a uniform and those who do not. As a matter of fact, some infection spared the civilian population while others felt with greater vengeance on this subgroup. Moreover, the incidence of different feared diseases was brought back to the rates of the late 19th Century. Thanks to a statistician, Giorgio Mortara (1885-1967) the impact of infective diseases in Wolrd War I on Italian demography is well established. Moreover, different military and civilian contribute to enrich the picture of the consequences of war. In conclusion World War I could see considered as a litmus paper. The litmus paper of successes and failures of italian public health management to face new medical challenges exacerbated by the crisis

POVIJEST SIFILISA U XVI. STOLJEĆU I KLJUČNA ULOGA LUIGIJA LUIGINIJA U RENESANSI

...Syphilis is the prime example of a “new disease” which triggered a transnational (European) discussion among physicians. It appeared between the end of the Middle Ages and the beginning of the Modern Times (at the beginning of the sixteenth century), a time in which medicine was changing from a dogmatic to an experimental discipline. The main changes were in the field of anatomy: in 1543, the same year of the astronomy-disrupting work by Nicolas Copernicus, the new less dogmatic and more empirical approach to anatomy by Andreas Vesalius was published. Nevertheless, in the Renaissance, medicine remains a tradition-bound discipline, proud of its millennial history and its superiority over the empirical, non-academic healers. When syphilis appeared in Europe, several explanations were elaborated. In the mid-16th century, an Italian doctor Luigi Luigini (born in 1526) published in Venice a collection of all the works on syphilis that appeared until 1566. He wanted to entrust to colleagues, contemporary and future, a compendium of all that was known about the “new” disease (the Latin term Novus means both “new” and “strange”). According to the most authors of the collection, the disease is in fact “new” and “strange”. Some authors of the collection find it impossible that authorities like Hippocrates and Galen overlooked it. Luigini’s work shows the authors’ effort to absorb syphilis in the corpus of academic medicine and affirm the authority of academic physicians against the empirical healers.Sifilis je važan primjer “nove bolesti” koja je pokrenula transnacionalnu (europsku) raspravu među liječnicima. Bolest se pojavila između kraja srednjeg vijeka i početka modernog doba (početkom 16. stoljeća), u vrijeme u kojem se medicina iz dogmatske mijenjala u eksperimentalnu disciplinu. Glavne promjene dogodile su se na polju anatomije: u 1543., istoj godini u kojoj se pojavio rad Nikole Kopernika, koji je promijenio zakone astronomije, objavljen je novi, manje dogmatični i više empirijski pristup anatomiji u radu Andreasa Vesaliusa. Ipak, u renesansi medicina ostaje disciplina vezana uz tradiciju, ponosna na svoju tisućljetnu povijest i svoju superiornost nad empirijskim, neakademskim iscjeliteljima. Kada se sifilis pojavio u Europi, nekoliko je objašnjenja detaljno izloženo. Sredinom 16. stoljeća, talijanski liječnik Luigi Luigini (rođen 1526.) objavio je u Veneciji zbirku svih djela o sifilisu koja su se pojavila do 1566. Želio je prenijeti svojim suvremenicima i budućim kolegama sažetak svega što je bilo poznato o “novoj bolesti” (latinski pojam Novus znači i “novi” i “čudan”). Prema većini autora zbirke, bolest je “nova” i “čudna”. Neki autori čiji se radovi pojavljuju u zbirci smatraju nemogućim da su najveći autoriteti, poput Hipokrata i Galena, previdjeli tu bolest. Luiginijevo djelo pokazuje napor autora da uvrste sifilis u korpus akademske medicine i potvrde autoritet akademskih liječnika nasuprot empirijskih iscjelitelja

Agroinoculation of Grapevine Pinot Gris Virus in tobacco and grapevine provides insights on viral pathogenesis

The Grapevine Pinot Gris disease (GPG-d) is a novel disease characterized by symptoms such as leaf mottling and deformation, which has been recently reported in grapevines, and mostly in Pinot gris. Plants show obvious symptoms at the beginning of the growing season, while during summer symptom recovery frequently occurs, manifesting as symptomless leaves. A new Trichovirus, named Grapevine Pinot gris virus (GPGV), which belongs to the family Betaflexiviridae was found in association with infected plants. The detection of the virus in asymptomatic grapevines raised doubts about disease aetiology. Therefore, the primary target of this work was to set up a reliable system for the study of the disease in controlled conditions, avoiding interfering factor(s) that could affect symptom development. To this end, two clones of the virus, pRI::GPGV-vir and pRI::GPGV-lat, were generated from total RNA collected from one symptomatic and one asymptomatic Pinot gris grapevine, respectively. The clones, which encompassed the entire genome of the virus, were used in Agrobacterium-mediated inoculation of Vitis vinifera and Nicotiana benthamiana plants. All inoculated plants developed symptoms regardless of their inoculum source, demonstrating a correlation between the presence of GPGV and symptomatic manifestations. Four months post inoculum, the grapevines inoculated with the pRI::GPGV-lat clone developed asymptomatic leaves that were still positive to GPGV detection. Three to four weeks later (i.e. ca. 5 months post inoculum), the same phenomenon was observed in the grapevines inoculated with pRI::GPGV-vir. This observation perfectly matches symptom progression in infected field-grown grapevines, suggesting a possible role for plant antiviral mechanisms, such as RNA silencing, in the recovery process.</div

Drp1 overexpression induces desmin disassembling and drives kinesin-1 activation promoting mitochondrial trafficking in skeletal muscle

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PTEN Loss as a Predictor of Tumor Heterogeneity and Poor Prognosis in Patients With EGFR-mutant Advanced Non-small-cell Lung Cancer Receiving Tyrosine Kinase Inhibitors

Background: Rapid disease progression of patients with advanced epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) has been recently associated with tumor heterogeneity, which may be mirrored by coexisting concomitant alterations. The aim of this analysis was to investigate the correlation between loss of function of PTEN and the efficacy of tyrosine kinase inhibitors in this population. Materials and Methods: Archival tumor blocks from patients with EGFR-mutant NSCLC who were administered upfront tyrosine kinase inhibitors were retrospectively collected. The status of 4 genes (PTEN, TP53, c-MET, IGFR) was evaluated by immunohistochemistry, and it was correlated with overall response rate, overall survival (OS), and progression-free survival (PFS). Results: Fifty-one patients were included. In multivariate analysis, PTEN loss (hazard ratio [HR], 3.46; 95% confidence interval [CI], 1.56-7.66; P = .002), IGFR overexpression (HR, 2.22; 95% CI, 1.03-4.77; P = .04), liver metastases (HR, 3.55; 95% CI, 1.46-8.65; P = .005), and Eastern Cooperative Oncology Group performance status (ECOG PS) &gt; 1 (HR, 2.57; 95% CI, 1.04-6.34; P = .04) were significantly associated with shorter PFS. Patients with PTEN loss had a median PFS of 6 months (2-year PFS, 11.6%), whereas patients without PTEN loss had a median PFS of 18 months (2-year PFS, 43.6%) (log-rank P &lt; .005). In the multivariate analysis, PTEN loss (HR, 5.92; 95% CI, 2.37-14.81; P &lt; .005), liver metastases (HR, 2.63; 95% CI, 1.06-6.51; P = .037), and ECOG PS &gt; 1 (HR, 2.80; 95% CI, 1.15-6.81; P = .024) were significantly associated with shorter OS. Patients with PTEN loss had a median OS of 6 months (2-year OS, 12.2%), whereas in patients without PTEN loss, OS was not reached (2-year OS, 63.9%) (log-rank P &lt; .0005).Conclusions: A low-cost and reproducible immunohistochemistry assay for PTEN loss analysis represents a potential tool for identifying tumor heterogeneity in patients with advanced EGFR-mutant NSCLC

Endocytic reawakening of motility in jammed epithelia.

Dynamics of epithelial monolayers has recently been interpreted in terms of a jamming or rigidity transition. How cells control such phase transitions is, however, unknown. Here we show that RAB5A, a key endocytic protein, is sufficient to induce large-scale, coordinated motility over tens of cells, and ballistic motion in otherwise kinetically arrested monolayers. This is linked to increased traction forces and to the extension of cell protrusions, which align with local velocity. Molecularly, impairing endocytosis, macropinocytosis or increasing fluid efflux abrogates RAB5A-induced collective motility. A simple model based on mechanical junctional tension and an active cell reorientation mechanism for the velocity of self-propelled cells identifies regimes of monolayer dynamics that explain endocytic reawakening of locomotion in terms of a combination of large-scale directed migration and local unjamming. These changes in multicellular dynamics enable collectives to migrate under physical constraints and may be exploited by tumours for interstitial dissemination

Inflation and Dark Energy from spectroscopy at z > 2

The expansion of the Universe is understood to have accelerated during two epochs: in its very first moments during a period of Inflation and much more recently, at z < 1, when Dark Energy is hypothesized to drive cosmic acceleration. The undiscovered mechanisms behind these two epochs represent some of the most important open problems in fundamental physics. The large cosmological volume at 2 < z < 5, together with the ability to efficiently target high-$z$ galaxies with known techniques, enables large gains in the study of Inflation and Dark Energy. A future spectroscopic survey can test the Gaussianity of the initial conditions up to a factor of ~50 better than our current bounds, crossing the crucial theoretical threshold of $\sigma(f_{NL}^{\rm local})$ of order unity that separates single field and multi-field models. Simultaneously, it can measure the fraction of Dark Energy at the percent level up to $z = 5$, thus serving as an unprecedented test of the standard model and opening up a tremendous discovery space