microRNAs and Inflammatory Immune Response in SARS-CoV-2 Infection: A Narrative Review

The current SARS-CoV-2 pandemic has emerged as an international challenge with strong medical and socioeconomic impact. The spectrum of clinical manifestations of SARS-CoV-2 is wide, covering asymptomatic or mild cases up to severe and life-threatening complications. Critical courses of SARS-CoV-2 infection are thought to be driven by the so-called “cytokine storm”, derived from an excessive immune response that induces the release of proinflammatory cytokines and chemokines. In recent years, non-coding RNAs (ncRNAs) emerged as potential diagnostic and therapeutic biomarkers in both inflammatory and infectious diseases. Therefore, the identification of SARS-CoV-2 miRNAs and host miRNAs is an important research topic, investigating the host–virus crosstalk in COVID-19 infection, trying to answer the pressing question of whether miRNA-based therapeutics can be employed to tackle SARS-CoV-2 complications. In this review, we aimed to directly address ncRNA role in SARS-CoV-2-immune system crosstalk upon COVID-19 infection, particularly focusing on inflammatory pathways and cytokine storm syndromes

in keeping with the spirit of the albertine statute constitutionalisation of the national unification

This chapter deals with the difficult process of constitutionalisation which characterised Italian Unification. Constitutionalisation is a long-term phenomenon which had the purpose of giving constitutional forms to the Nation. The promulgation of the Albertine Statute is more the start than the arrival of this phenomenon. The focus of this investigation is, therefore, to study the Constitution through its evolution paying particular attention to the process of legal integration within the structures of the Albertine Statute and to the amendment mechanisms of the constitutional text. The preamble of the Albertine Statute speaks of «perpetual and irrevocable fundamental law». The word «perpetual» meant the prohibition of revoking constitutional concession, while the word «irrevocable» was intended as a pact between the Sovereign and the Nation. Over the years, very few were the changes to the letter of the Albertine Statute. The interpretation and the practice represented the most important mechanisms of constitutional change (implicit constitutional changes). A primary role was acknowledged to non-written norms. In this perspective, it may well be said that the Italian Constitution consisted in something more than the written text and dwelt in the spirit and not in the letter of the Albertine Statute

Time-dependent brittle creep in Darley Dale sandstone

The characterization of time-dependent brittle rock deformation is fundamental to understanding the long-term evolution and dynamics of the Earth's crust. The chemical influence of pore water promotes time-dependent deformation through stress corrosion cracking that allows rocks to deform at stresses far below their short-term failure strength. Here, we report results from a study of time-dependent brittle creep in water-saturated samples of Darley Dale sandstone (initial porosity, 13%) under triaxial stress conditions. Results from conventional creep experiments show that axial strain rate is heavily dependent on the applied differential stress. A reduction of only 10% in differential stress results in a decrease in strain rate of more than two orders of magnitude. However, natural sample variability means that multiple experiments must be performed to yield consistent results. Hence we also demonstrate that the use of stress-stepping creep experiments can successfully overcome this issue. We have used the stress-stepping technique to investigate the influence of confining pressure at effective confining pressures of 10, 30, and 50 MPa (while maintaining a constant 20 MPa pore fluid pressure). Our results demonstrate that the stress corrosion process appears to be significantly inhibited at higher effective pressures, with the creep strain rate reduced by multiple orders of magnitude. The influence of doubling the pore fluid pressure, however, while maintaining a constant effective confining pressure, is shown to influence the rate of stress corrosion within the range expected from sample variability. We discuss these results in the context of microstructural analysis, acoustic emission hypocenter locations, and fits to proposed macroscopic creep laws

Adult-onset still’s disease: Novel biomarkers of specific subsets, disease activity, and relapsing forms

Adult-onset Still’s disease (AOSD) is a systemic inflammatory disease of unknown etiology. Recent studies have demonstrated that the hallmark of AOSD is a cytokine storm, which is characterized by the excessive production of interleukin (IL)-1, IL-6, IL-18, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), suggesting how pro-inflammatory cytokines play an important role in the pathogenesis of this disease. Actually, a certain proportion of patients (around 17–32%) with severe clinical symptoms achieves only partial remission or is resistant to both first-line corticosteroids and second-line DMARDs. These patients are defined as refractory AOSD patients, requiring higher dosage glucocorticoids, longer treatment duration, or the simultaneous introduction of immunosuppressive drugs, further leading to AOSD relapses. In this narrative review, we will analyze the latest literature data to unravel potential pathogenetic factors associated with specific patterns of AOSD disease or relapses in order to identify biomarkers that may guide clinical decisions, eventually leading to new therapeutic options

Reply to: “Herpes zoster seven days after SARS-CoV-2 vaccination in a patient with ankylosing spondylitis under adalimumab” by Josef Finsterer

Several guidelines suggest investigating the incidence and prevalence of vaccine-preventable infections in adult patients with autoimmune or inflammatory diseases; consequently, the effect and safe-ty issues of vaccination are under careful examination. Moreover, immunosup-pression and immunodeficiency were con-traindications for the previously available vaccine in the past years, thus live zoster vaccine was originally recommended for immunocompetent adults aged ≥50 years, leading to an unmet need for vaccination against HZ in immunocompromised adults. Considering all these efforts and the current pandemic challenge, we be-lieve that now more than ever we are asked to quickly detect potential adverse events, even extremely rare and mild ones, and to face them, in order to support the robust pharmacovigilance campaign for SARS-CoV2 vaccination

Macchine musicali e panorami: il viaggio virtuale nella geografia della nazione

In the early 19th century the corporal and sensitive immersion in the panoramic narrative of maplike loci allowed to transform the visitor-spectator into a lifeless consumer of the geographical representation of the unity of capitalistic strategies and ideological propaganda, thus anticipating the rise of 21st-century experience of dislocation by digital virtual reality

Erythema nodosum after COVID-19 vaccine

: The current coronavirus disease 2019 (COVID-19) pandemic is a global challenge with strong medical and socioeconomic implications. Hopes have been placed in the development of various vaccines. As the vaccination campaign is in progress, adverse effects need to be monitored closely. Possible side effects range from minor events to more serious manifestations. In this article, we describe two cases of erythema nodosum (EN) after COVID-19 vaccination in two previously healthy female patients of 59 and 51 years, respectively. Most of the usual etiologies of EN were excluded by laboratory testing. EN was successfully treated with corticosteroids. Remarkably, in the first case, a relapse occurred 48 hours after the second dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. In this case series, we describe two unusual occurrences of EN after vaccination with an mRNA COVID-19 vaccine and a viral vector vaccine, respectively, and we discuss the available related literature

The Role of Ultrasound in Temporomandibular Joint Disorders: An Update and Future Perspectives

Temporomandibular joint (TMJ) disorder is the second most common chronic pain condition affecting the general population after back pain. It encompasses a complex set of conditions, manifesting with jaw pain and limitation in mouth opening, influencing chewing, eating, speaking, and facial expression. TMJ dysfunction could be related to mechanical abnormalities or underlying inflammatory arthropathies, such as rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA). TMJ exhibits a complex anatomy, and thus a thorough investigation is required to detect the TMJ abnormalities. Importantly, TMJ involvement can be completely asymptomatic during the early stages of the disease, showing no clinically detectable signs, exposing patients to delayed diagnosis, and progressive irreversible condylar damage. For the prevention of JIA complications, early diagnosis is therefore essential. Currently, magnetic resonance imaging (MRI) is described in the literature as the gold standard method to evaluate TMJ. However, it is a high-cost procedure, not available in all centers, and requires a long time for image acquisition, which could represent a problem notably in the pediatric population. It also suffers restricted usage in patients with claustrophobia. Ultrasonography (US) has emerged in recent years as an alternative diagnostic method, as it is less expensive, not invasive, and does not demand special facilities. In this narrative review, we will investigate the power of US in TMJ disorders based on the most relevant literature data, from an early screening of TMJ changes to differential diagnosis and monitoring. We then propose a potential algorithm to optimize the management of TMJ pathology, questioning what would be the role of ultrasonographic study

Flu-like syndrome, bronchoconstriction and fever caused by 5-methoxypsoralen: the first case report and literature review.

Photochemotherapy with psoralens and UVA (PUVA) is a very effective therapeutic option based on the interaction of a photoactive drug and light usually employed for the treatment of psoriasis and of other skin disorders, such as atopic dermatitis, vitiligo, and cutaneous lymphoma. The psoralens most widely used for oral PUVA are 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP), tricyclic furocoumarins naturally present in a large number of plants. The chemical formula and the molecular composition of 5-MOP and 8-MOP present only slight differences, however these are sufficient to make them two different chemical compounds capable of different reactions and interactions. PUVA is generally well tolerated, but adverse events may occur. Besides the photosensitizing effect, which represents the therapeutic basis of PUVA, the commonest side effects complained of by the patients after oral intake of psoralens are nausea, vomiting, anorexia (mainly for 8-MOP), insomnia, anxiety, headache. Although very rarely or exceptionally, a series of potentially serious side effects has also been referred: while anaphylaxis has been reported due to both oral 5-MOP and 8-MOP, exanthematous drug reaction, urticaria, bronchoconstriction, asthma exacerbation, drug fever and flu-like symptoms such as headache, fatigue, muscle aches have been published related to 8-MOP intake only. To our knowledge, in fact, none of the above mentionated symptoms have been associated to oral 5-MOP in literature. Our report describes a case of fever, bronchoconstriction and flu-like syndrome in a patient during PUVA therapy with oral 5-methoxypsoralen