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Background: Cone Beam Computed Tomography (CBCT) represents the optimal imaging solution for the evaluation of the maxillofacial and dental area when quantitative geometric and volumetric accuracy is necessary (e.g., in implantology and orthodontics). Moreover, in recent years, this technique has given excellent results for the imaging of lower and upper extremities. Therefore, significant interest has been increased in using CBCT to investigate larger and non-traditional anatomical districts. Objective: The purpose of this work is to review the scientific literature in Pubmed and Scopus on CBCT application beyond head districts by paying attention to image quality and radiological doses. Methods: The search for keywords was conducted in Pubmed and Scopus databases with no back-date restriction. Papers on applications of CBCT to head were excluded from the present work. From each considered paper, parameters related to image quality and radiological dose were extracted. An overall qualitative evaluation of the results extracted from each issue was done by comparing the conclusive remarks of each author regarding doses and image quality. PRISMA statements were followed during this process. Results: The review retrieved 97 issues from 83 extracted papers; 46 issues presented a comparison between CBCT and Multi-Detector Computed Tomography (MDCT), and 51 reviewed only CBCT. The radiological doses given to the patient with CBCT were considered acceptable in 91% of cases, and the final image quality was found in 99%. Conclusion: CBCT represents a promising technology not only for imaging of the head and upper and lower extremities but for all the orthopedic districts. Moreover, the application of CBCT derived from C-arms (without the possibility of a 360 ° rotation range) during invasive investigations demonstrates the feasibility of this technique for non-standard anatomical areas, from soft tissues to vascular beds, despite the limits due to the incomplete rotation of the tube.

Concern about the radiation dose to children from diagnostic radiology examinations has recently been popularly expressed, particularly related to Computed Tomography (CT) procedures. The common belief is that children receive higher doses compared to adults since the optimization of the procedure settings for different anatomies are not always implemented (i.e., FOV, kV and mA not optimized for children). Since the dosimetric quantities related to effective dose are essentially defined for adults, it becomes important to study and propose methods applicable also to pediatric cases. In current clinical and radiological practice, sizes, shapes, and data for pediatric organs are commonly derived from adult ones, but these statements do not reduce dosimetric problems at the definition of scaling algorithms. The aim of this study is to analyze the differences in pediatric vs adult dosimetry, starting from measured organ doses in cone-beam computed tomography (CBCT) procedures for maxillofacial region. Two different anthropomorphic phantoms (child vs adult phantoms) were scanned, acquiring all data: results will be presented in terms of organ and derived doses, discussing approaches and differences.

Carbon dioxide (CO2) angiography represents an important technique to overcome most clinical problems related to the use of iodine contrast medium. The recent technologic advancements in the fields of gas injection and image reconstructions made CO2 angiography a very efficient method for clinical evaluation of peripheral cardiovascular system. Despite that, some challenges are still open and a better knowledge of the biomechanical behavior of CO2 and its interactions with blood flowing into the vessels is necessary to optimize this technology and to expand its field of application. This paper presents a quick overview about biomechanical behavior of carbon dioxide during injection, suggesting possible optimization tricks to make CO2 angiography procedures more effective to improve imaging and reduce the patients’ radiological dose. Particular attention has been also paid to 3D imaging techniques, which can certainly be opened to the use of carbon dioxide.

The understanding of the use of Magnolia officinalis L. (Magnoliaceae) as a possible dietary supplement for supporting the treatment of airway pathologies might be of clinical interest. Two commercially available bark extracts (M. officinalis extract [MOE]) were characterized by quantitation in honokiol and magnolol content by means of high-performance liquid chromatography with UV detection. MOE effects, as well as those of the reference compounds per se, on some targets connected to airway pathologies (antibacterial- and lung and trachea relaxing- activities) were investigated. Results showed that MOE possessed interesting antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pneumoniae. This was accompanied by a spasmolytic and antispasmodic activity, possibly owing to its ability to concurrently modulate different targets such as H-1-, beta(2)- and muscarinic receptors and l-type calcium channels involved in bronchodilation. All these effects were directly related to the MOE content in honokiol and magnolol. In conclusion, the properties of MOE highlighted here strongly encourage its application as dietary supplement in the treatment of airway diseases.

Background In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a “public health emergency of international concern”. A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. Methods We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. Results SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. Conclusions Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.

In December 2019, a novel human-infecting coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), was recognised to cause a pneumonia epidemic outbreak with different degrees of severity in Wuhan, Hubei Province in China. Since then, this epidemic has spread worldwide; in Europe, Italy has been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, few studies about SARS-CoV-2 concerning its immunopathogenesis and treatment are available. On the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82 % of genome homology) and that its characteristics, like the modality of transmission or the type of the immune response it may stimulate, are still poorly known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: (1) the structure of SARS-CoV-2 and SARS-CoV; (2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the cytokine release syndrome; (3) the modification of the cell microRNome and of the immune response in patients with SARS infection; and (4) the possible role of some fat-soluble compounds (such as vitamins A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.

The purpose of this work was to outline some practical rules for pressure and volume settings in automatic CO2 injection angiographic procedures focusing on the iliac arterial system, since, in current clinical practice, each operator uses his personal experience to obtain imaging results which are not always easy to compare. A theoretical model was thus developed and then verified by a mechanical simulator of the aortoiliac vascular system, with constant and pulsatile blood flow. The conditions of forward and reverse flows have been described, both for constant and pulsatile regimens and pressures, flows, and optical images of the bubbles in glass vessels were simultaneously acquired, analyzed and compared. Our results demonstrated that “good” radiological images (adequate to patient's conditions and clinical need) are strictly related to appropriate settings of gas injection pressure and flow, in accordance with two simple operative rules. These rules prescribe that the patient's pressure, the blood flow in the vessel, and the hydraulic resistance of the gas injection line be known: the first two parameters may be estimated, while the third must be experimentally measured. By following these rules, it is possible to obtain the best results for each clinical setting, a more standardized approach and better imaging during angiographic procedures with carbon dioxide as contrast medium.

Waste represents a cost for companies, in particular for agro-food companies, which can become a resource as a secondary material. In this work, we examine three products of olive-oil waste water, named MOMAST® (Plus30, PW25, and HY100). Based on the chemical composition, obtained with different methods, we hypothesized a possible application as food supplements in irritable bowel syndrome (IBS). We therefore studied MOMASTs on some targets linked to this pathology: antioxidant action and spontaneous and induced intestinal contractility of the ileum and colon. Plus30, which showed a more promising biological of activity also for its oleuropein content, was characterized by an interesting action against some microorganisms. The results highlighted the ability of Plus30 to modulate spontaneous and induced contractility, to exert a good antioxidant action, and to significantly act on various microorganisms. These effects are synergistic in the presence of antibiotics. In conclusion, we can confirm that Plus30 could be a great candidate as a food supplement in patients with IBS.

Rigorous clinical evaluation of the physiological performance is currently performed with complex and long procedures which need expensive technology and skilled operators. In a wide range of situations (frail patients, daily clinical practice, etc.), these approaches are difficult to be applied and simpler tests, with a lack of scientific background, are mandatory. To avoid these problems, we propose a test (test of physiological performance (TOPP)) to evaluate the physiological behavior of a subject, in a really easy and safe clinical setting, measuring only the heart rate. The subject is submitted to an active standing-up test and then two submaximal exercises (with a low power load) on a cycle-ergometer. The heart rate modifications due to each submaximal step are analyzed by exponential interpolation to calculate the ascending and descending time constants and evaluate the way each subject adapts his heart rate to work. The standard deviation of the RR for each stationary phase (warm-up, load, recovery) was calculated as an index of short-term variability. Then a standard Fourier analysis of the stationary periods of the standing-up procedures allows to quickly and easily evaluate the autonomic nervous activation. We tested the protocol on five healthy subjects to verify the feasibility and the acceptance of the procedure. The five subjects demonstrated a good tolerance of the entire procedure. The standing-up showed a behavior of the autonomic system consistent with the physiology (with an increase in sympathetic activation in the passage to standing position). The analysis of the two submaximal steps highlights how younger and trained subjects present lower heart rates (both in the ascending phase and in the recovery) with a quicker adaptation ability (smaller time constants) consistent with what is expected. The short-term variability of heart rate is greater in young and trained subjects, thus confirming how the sympatho-vagal balance, in these subjects, is more dynamic. The proposed test is well tolerated by the subjects and the results, albeit in a small cohort of healthy volunteers, are consistent with what is expected from physiology and is already present in the literature. Our work aims to be a proposal with a feasibility check of a method for evaluating performance. The work to be done for the clinical validation of the TOPP is still long, but we are aware that it can give important results and that the TOPP can become an effective tool for the assessment of the physiological performance even of fragile subjects.

COronaVIrus Disease 2019 (COVID-19) is a newly emerging infectious disease that spread across the world, caused by the novel coronavirus Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). Despite the advancements in science that led to the creation of the vaccine, there is still an urgent need for new antiviral drugs effective against SARS-CoV-2. This study aimed to investigate the antiviral effect of Paulownia tomentosa Steud extract against SARS-CoV-2 and to evaluate its antioxidant properties, including respiratory smooth muscle relaxant effects. Our results showed that P. tomentosa extract can inhibit viral replication by directly interacting with both the 3-chymotrypsin-like protease and spike protein. In addition, the phyto complex does not reduce lung epithelial cell viability and exerts a protective action in those cells damaged by tert-butyl hydroperoxide , a toxic agent able to alter cells' functions via increased oxidative stress. These data suggest the potential role of P. tomentosa extract in COVID-19 treatment, since this extract is able to act both as an antiviral and a cyto-protective agent in vitro.

The main purpose of this review is to analyze published data concerning the antioxidant properties of astaxanthin, a xanthophyll, produced by the microalga Haematococcus pluvialis in response to specific conditions of “environmental stress” and characterized by its typical deep red color. Natural astaxanthin establishes effective protections against oxidative stress, neutralizing free radicals in both the inner and outer layer of cell membranes, especially in mitochondria. The most recent preclinical and clinical studies that have investigated the beneficial properties of this molecule toward the gastrointestinal tract were included.

It is well known that diet and nutrition play a critical role in the etiopathogenesis of many disorders. On the other hand, nutrients or bioactive compounds can specifically target and control various aspects of the mechanism underlying the pathology itself, and, in this context, diseases related to intestinal motility disorders stand out. The Herbal Mix (HM) consisting of Olea europea L. leaf (OEE) and Hibiscus sabdariffa L. (HSE) extracts (13:2) has been proven to be a promising nutraceutical option for many diseases, but its potential in inflammatory-driven gastrointestinal disorders is still unexplored. In this study, HM effects on guinea-pig ileum and colon contractility (induced or spontaneous) and on human iNOS activity, as well as on human colorectal adenocarcinoma Caco-2 cells, were studied. Results showed that the HM can control the ileum and colon contractility without blocking the progression of the food bolus, can selectively inhibit iNOS and possesses a strong pro-apoptotic activity towards Caco-2 cells. In conclusion, the present results suggest that, in some diseases, such as those related to motility disorders, an appropriate nutritional approach can be accompanied by a correct use of nutraceuticals that could help not only in ameliorating the symptoms but also in preventing more severe, cancer-related conditions.

Nowadays, technological progress has equipped clinicians with new useful devices for the collection, analysis and presentation of data. As a consequence, many diseases and pathological conditions have been studied in a more detailed way, sometimes with remarkable results. In fact, they are not always validated by the old physiological models. In this respect, we present the case of low gradient severe aortic stenosis, a condition characterised by a small aortic valve area and a low-pressure gradient. According to the mathematical and physical assumptions these readings are contradictory whereas the Doppler-echocardiography shows clearly the existence of such a situation. In this work, we have described the physiological base of this phenomenon and discussed the limitations of the technology used. In this work, we are going to analyse some conditions commonly observed in daily clinical practice in order to prompt a critical outlook in both clinicians and technicians about the instrumentations used and the methods applied.

SARS-CoV-2 is the etiological agent of the current pandemic worldwide and its associated disease COVID-19. In this review, we have analyzed SARS-CoV-2 characteristics and those ones of other well-known RNA viruses viz. HIV, HCV and Influenza viruses, collecting their historical data, clinical manifestations and pathogenetic mechanisms. The aim of the work is obtaining useful insights and lessons for a better understanding of SARS-CoV-2. These pathogens present a distinct mode of transmission, as SARS-CoV-2 and Influenza viruses are airborne, whereas HIV and HCV are bloodborne. However, these viruses exhibit some potential similar clinical manifestations and pathogenetic mechanisms and their understanding may contribute to establishing preventive measures and new therapies against SARS-CoV-2.

BACKGROUND The proton pump inhibitors (PPIs), used to reduce gastric acid secretion, represent one of the most widely used pharmaceutical classes in the world. Their consumption as a risk factor for the evolution of severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been investigated as well as the mortality of these patients. These risks also appear to be linked to the duration and the dosage. On the other hand, several studies have emerged with regard to the protective or therapeutic effects of these drugs. More and more evidence underlines the immunomodulatory and anti-fibrotic role of PPIs. In addition, their ability to alkalize the contents of endosomes and lysosomes serves as an obstacle to the entry of the virus into the host cells. AIM To identify studies on the relationship between the intake of PPIs and coronavirus disease 2019 (COVID-19) in patients affected by SARS-CoV-2 infection, with the main objective of evaluating the outcomes related to severity and mortality. METHODS A literature review was performed in November 2020. The MEDLINE/PubMed, Cochrane Library, EMBASE and Google Scholar databases were searched for all relevant articles published in English on this topic. The search terms were identified by means of controlled vocabularies, such as the National Library of Medicine’s MESH (Medical Subject Headings) and keywords. The MESH terms and keywords used were as follows: “COVID-19”, “proton pump inhibitors”, ”PPIs”, “SARS-CoV-2”, “outcomes”, “severity” and “mortality”. The inclusion criteria regarding the studies considered in our analysis were: meta-analysis, case-control, hospital-based case-control, population-based case-control, retrospective studies, online survey, as well as cohort-studies, while articles not published as full reports, such as conference abstracts, case reports and editorials were excluded. We tried to summarize and pool all the data if available. RESULTS A total of 9 studies were found that described the use of PPIs, of which only 5 clearly reported the severity and mortality data in SARS-CoV-2 patients. Our pooled incidence analysis of severe events did not differ between patients with and without PPIs (odds ratio 1.65, 95% confidence interval: 0.62-4.35) (P = 0.314), or for mortality (odds ratio 1.77, 95% confidence interval: 0.62-5.03) (P = 0.286). CONCLUSION Detailed and larger case studies are needed to accurately understand the role of PPIs in this viral infection.

Background: Lubeluzole, a neuroprotective anti-ischemic drug, was tested for its ability to act as both antibiotic chemosensitizing and antipropulsive agent for the treatment of infectious diarrhea. Methods: In the present report, the effect of lubeluzole against antidiarrheal target was tested. The antimicrobial activity towards Gram-positive and Gram-negative bacteria was investigated together with its ability to affect ileum and colon contractility. Results: Concerning the antimicrobial activity, lubeluzole showed synergistic effects when used in combination with minocycline against four common Gram-positive and Gram-negative bacteria (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922), although relatively high doses of lubeluzole were required. In ex vivo experiments on sections of gut smooth muscles, lubeluzole reduced the intestinal contractility in a dose-dependent manner, with greater effects observed on colon than on ileum, and being more potent than reference compounds otilonium bromide and loperamide. Conclusion: All above results identify lubeluzole as a possible starting compound for the development of a novel class of antibacterial adjuvants endowed with spasmolytic activity. Graphic abstract: [Figure not available: see fulltext.]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a potentially life-threatening disease, defined as Coronavirus Disease 19 (COVID-19). The most common signs and symptoms of this pathological condition include cough, fever, shortness of breath, and sudden onset of anosmia, ageusia, or dysgeusia. The course of COVID-19 is mild or moderate in more than 80% of cases, but it is severe or critical in about 14% and 5% of infected subjects respectively, with a significant risk of mortality. SARS-CoV-2 related infection is characterized by some pathogenetic events, resembling those detectable in other pathological conditions, such as sepsis and severe acute pancreatitis. All these syndromes are characterized by some similar features, including the coexistence of an exuberant inflammatory- as well as an anti-inflammatory-response with immune depression. Based on current knowledge concerning the onset and the development of acute pancreatitis and sepsis, we have considered these syndromes as a very interesting paradigm for improving our understanding of pathogenetic events detectable in patients with COVID-19. The aim of our review is: 1)to examine the pathogenetic mechanisms acting during the emergence of inflammatory and anti-inflammatory processes in human pathology; 2)to examine inflammatory and anti-inflammatory events in sepsis, acute pancreatitis, and SARS-CoV-2 infection and clinical manifestations detectable in patients suffering from these syndromes also according to the age and gender of these individuals; as well as to analyze the possible common and different features among these pathological conditions; 3)to obtain insights into our knowledge concerning COVID-19 pathogenesis. This approach may improve the management of patients suffering from this disease and it may suggest more effective diagnostic approaches and schedules of therapy, depending on the different phases and/or on the severity of SARS-CoV-2 infection.

A new Thymus vulgaris L. solid essential oil (SEO) formulation composed of liquid EO linked to solid excipients has been chemically analysed and evaluated for its intestinal spasmolytic and antispastic effects in ex vivo ileum and colon of guinea pig and compared with liquid EO and excipients. Liquid EO and solid linked EO were analysed by original capillary electrochromatography coupled to diode array detection (CEC-DAD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodologies. The main bioactive constituents are thymol and carvacrol, with minor constituents for a total of 12 selected analysed compounds. Liquid EO was the most effective in decreasing basal contractility in ileum and colon, excipients addiction permitted normal contractility pattern in solid linked EO SEO. In ileum and colon, the Thymus vulgaris L. solid formulation exerted the relaxant activity on K+-depolarized intestinal smooth muscle as well as liquid EO. The solid essential oil exhibits antimicrobial activity against different strains (Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, Escherichia coli, Salmonella Thyphimurium, Candida albicans) similarly to liquid oil, with activity against pathogen, but not commensal strains (Bifidobacterium Breve, Lactobacillus Fermentum) in intestinal homeostasis. Therefore, Thymus vulgaris L. solid essential oil formulation can be proposed as a possible spasmolytic and antispastic tool in medicine.

Inflammation is an essential protective response against harmful stimuli, such as invading pathogens, damaged cells, or irritants. Physiological inflammation eliminates pathogens and promotes tissue repair and healing. Effective immune response in humans depends on a tightly regulated balance among inflammatory and anti-inflammatory mechanisms involving both innate and adaptive arms of the immune system. Excessive inflammation can become pathological and induce detrimental effects. If this process is not self-limited, an inappropriate remodeling of the tissues and organs can occur and lead to the onset of chronic degenerative diseases. A wide spectrum of infectious and non-infectious agents may activate the inflammation, via the release of mediators and cytokines by distinct subtypes of lymphocytes and macrophages. Several molecular mechanisms regulate the onset, progression, and resolution of inflammation. All these steps, even the termination of this process, are active and not passive events. In particular, a complex interplay exists between mediators (belonging to the group of Eicosanoids), which induce the beginning of inflammation, such as Prostaglandins (PGE2), Leukotrienes (LT), and thromboxane A2 (TXA2), and molecules which display a key role in counteracting this process and in promoting its proper resolution. The latter group of mediators includes: ω-6 arachidonic acid (AA)-derived metabolites, such as Lipoxins (LXs), ω -3 eicosapentaenoic acid (EPA)-derived mediators, such as E-series Resolvins (RvEs), and ω -3 docosahexaenoic (DHA)-derived mediators, such as D-series Resolvins (RvDs), Protectins (PDs) and Maresins (MaRs). Overall, these mediators are defined as specialized pro-resolving mediators (SPMs). Reduced synthesis of these molecules may lead to uncontrolled inflammation with possible harmful effects. ω-3 fatty acids are widely used in clinical practice as rather inexpensive, safe, readily available supplemental therapy. Taking advantage of this evidence, several researchers are suggesting that SPMs may have beneficial effects in the complementary treatment of patients with severe forms of SARS-CoV-2 related infection, to counteract the "cytokine storm" observed in these individuals. Well-designed and sized trials in patients suffering from COVID-19 with different degrees of severity are needed to investigate the real impact in the clinical practice of this promising therapeutic approach.

Background—It is recognized that inflammation is an underlying cause of dry eye disease (DED), with cytokine release involved. We systematically reviewed literature with meta-analyses to quantitatively summarize the levels of tear cytokines in DED. Methods—The PubMed, Embase, Web of Science, Ovid, Cochrane, and Scopus databases were reviewed until September 2019, and original articles investigating tear cytokines in DED patients were included. Differences of cytokines levels of DED patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed by applying Newcastle-Ottawa-Scale and the GRADE quality score. Methods of analytical procedures were included as covariate. Results—Thirteen articles investigating 342 DED patients and 205 healthy controls were included in the meta-analysis. The overall methodological quality of these studies was moderate. Systematic review of the selected articles revealed that DED patients had higher tear levels of interleukin (IL)-1β, IL-6, chemokine IL-8, IL-10, interferon-γ, IFN-γ, and tumor necrosis factor-α, TNF-α as compared to controls. Evidence was less strong for IL-2 and IL-17A. Conclusions—Data show that levels of tear cytokines in DED and control display a great variability, and further studies of higher quality enrolling a higher number of subjects are needed, to define a cut-off value.

There has been an ongoing technological evolution and impact of medical instrumentation on cardiovascular patient care during the last fifty years, and it is now impossible to manage the diagnostic and therapeutic process without adequate instrumental support. This trend has radically modified the professional activity of most healthcare personnel but it has not always been flanked by appropriate professional training. In particular, professional nursing schools are resistant to open their courses to technological aspects and in the rare cases of interest, have major difficulties finding qualified teachers with clinical experience and an aptitude for instrumental procedures