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Allergic diseases, such as respiratory, cutaneous, and food allergy, have dramatically increased in prevalence over the last few decades. Increasing use of antibiotics has been linked with dysbiosis and enhanced prevalence of allergies and asthma. Despite the clear involvement of the microbiome in atopic disease, it remains to be determined whether microbial alterations are a cause or a consequence of the disease. Human microbiota is defined as the multitude of microorganisms that live in or are associated with a variety of human tissues: the gut, respiratory tract, skin and genital tract. Recent advances in metagenomic sequencing and bioinformatics have enabled detailed characterization of these vital microbial communities and their role in different diseases. In particular, the relationship of microbiota with immune responses and immunological or allergic diseases is well known. The composition of gut, respiratory and skin microbiota can influence systemic inflammatory responses that mediate food allergy, rhinitis, asthma, immunodeficiency diseases, atopic dermatitis and chronic urticaria. This review discusses the role of microbiota in the major allergic Type 2 diseases evaluating the composition of the main commensal bacteria species and their relation with these pathologies.

Until now, the ability to form a self-assembled monolayer (SAM) on a surface has been investigated according to deposition techniques, which in turn depend on surface-coater interactions. In this paper, we pursued two goals: to form a SAM on a gold nanosurface and to correlate its formation to the nanosurface curvature. To achieve these objectives, gold nanoparticles of different shapes (spheres, rods, and triangles) were functionalized with a luminescent thiolated bipyridine (Bpy-SH), and the SAM formation was studied by investigating the photo-physics of Bpy-SH. We have shown that emission wavelength and excited-state lifetime of Bpy-SH are strongly correlated to the formation of specific aggregates within SAMs, the nature of these aggregates being in close correlation to the shape of the nanoparticles. Micro-Raman spectroscopy investigation was used to test the SERS effect of gold nanoparticles on thiolated bipyridine forming SAMs.

Cancer is one of the most widespread diseases globally and one of the leading causes of death. Known cancer treatments are chemotherapy, surgery, radiation therapy, targeted hormonal therapy, or a combination of these methods. Antitumor drugs, with different mechanisms, interfere with cancer growth by destroying cancer cells. However, anticancer drugs are dangerous, as they significantly affect both cancer cells and healthy cells. In addition, there may be the onset of systemic side effects perceived and mutagenicity, teratogenicity, and further carcinogenicity. Many polyphenolic extracts, taken on top of common anti-tumor drugs, can participate in the anti-proliferative effect of drugs and significantly reduce the side effects developed. This review aims to discuss the current scientific knowledge of the protective effects of polyphenols of the genera Vaccinium, Citrus, Olea, and Cynara on the side effects induced by four known chemotherapy, Cisplatin, Doxorubicin, Tamoxifen, and Paclitaxel. In particular, the summarized data will help to understand whether polyphenols can be used as adjuvants in cancer therapy, although further clinical trials will provide crucial information.

Hypersensitivity reactions (HRs) to contrast media (CM) are a major problem. We compared differences of HRs to iodinated contrast media (ICM) versus gadolinium-based contrast media (GBCM), collecting data on prevalence, type, latency and severity. Secondly, the predisposition to perform new contrast tests, use of premedication and possible appearance of new reactions were explored in a long-term follow-up of 5 years. Clinical data, comorbidities, skin test (ST) results, re-exposure to CM procedures with any new reactions, premedication and CM used were collected. In a retrospective single-center study, 350 patients with mild to moderate HRs were enrolled. Asthma, food allergy, non-allergic drug hypersensitivity and neurologic disease were significantly more frequent in patients with HRs to GBCM compared to the high evidence of cardiovascular disease and history of cancer in patients with HRs to ICM. A marked delay in performing STs was reported by patients with negative results (66 months, p < 0.01). Iomeprol, iopamidol and gadobenic acid were the culprit CM most involved in HRs in patients with positive STs. During follow-up, 7.1% of responders reported new HRs to CM despite negative STs, premedication and infusion of alternative CM in most cases.

Asthma is a heterogeneous disease usually characterized by chronic airway inflammation and recognized as the most prevalent chronic illness among children. Despite this, the knowledge as to how asthma affects adolescents is still scarce. One of the main management problems of asthmatic adolescents is the poor adherence to pharmacological and non-pharmacological treatments. The assessment of respiratory function and the impact on quality of life are still two crucial challenges in the management of asthmatic adolescents. Additionally, the COVID-19 pandemic has prompted physicians to explore complementary management strategies including telemedicine technologies. This review aims to provide an update on the contribution of respiratory functional tests, how asthma affects quality of life of adolescents and, finally, how telemedicine contributes to the management of adolescent asthmatics during the COVID-19 pandemic.

Background: The inappropriate use of antibiotics has increased selective pressure and the spread of multi-drug-resistant (MDR) pathogens, which reduces the possibility of effective treatment. A potential alternative therapeutic approach may be represented by essential oils, such as the distilled extract of bergamot (Citrus bergamia Risso et Poiteau). Such natural products exercise numerous biological activities, including antimicrobial effects. Methods: This work aimed to evaluate the kinetics of the bactericidal and fungicidal activity of the distilled extract of bergamot on MDR bacteria and fungi from clinical specimens using the time-kill assay. Furthermore, the antimicrobial activity of the distilled extract of bergamot on the morphology and cellular organization of clinical pathogens was evaluated by confocal laser scanning microscopy. Results: Our results demonstrated that the distilled extract of bergamot exhibited significant antimicrobial activity and a specific bactericidal effect against the bacterial and fungal strains tested. Furthermore, confocal microscope images clearly showed compromised membrane integrity, damage and cell death in bacterial samples treated with the distilled extract of bergamot. In addition, progressive alterations in cell-wall composition, cytoplasmic material and nucleus structure triggered by exposure to the distilled extract of bergamot were identified in the fungal samples considered. Conclusions: Our data suggest that the use of essential oils, such as distilled extract of bergamot (Citrus bergamia Risso et Poiteau), can represent a valid alternative therapeutic strategy to counteract antibiotic resistance of pathogens.

The maintenance of the physiological values of blood pressure is closely related to unchangeable factors (genetic predisposition or pathological alterations) but also to modifiable factors (dietary fat and salt, sedentary lifestyle, overweight, inappropriate combinations of drugs, alcohol abuse, smoking and use of psychogenic substances). Hypertension is usually characterized by the presence of a chronic increase in systemic blood pressure above the threshold value and is an important risk factor for cardiovascular disease, including myocardial infarction, stroke, micro- and macro-vascular diseases. Hypertension is closely related to functional changes in the endothelium, such as an altered production of vasoconstrictive and vasodilator substances, which lead to an increase in vascular resistance. These alterations make the endothelial tissue unresponsive to autocrine and paracrine stimuli, initially determining an adaptive response, which over time lead to an increase in risk or disease. The gut microbiota is composed of a highly diverse bacterial population of approximately 1014 bacteria. A balanced intestinal microbiota preserves the digestive and absorbent functions of the intestine, protecting from pathogens and toxic metabolites in the circulation and reducing the onset of various diseases. The gut microbiota has been shown to produce unique metabolites potentially important in the generation of hypertension and endothelial dysfunction. This review highlights the close connection between hypertension, endothelial dysfunction and gut microbiota.

Objectives COVID-19 causes lung parenchymal and endothelial damage that lead to hypoxic acute respiratory failure (hARF). The influence of hARF severity on patients’ outcomes is still poorly understood.Design Observational, prospective, multicentre study.Setting Three academic hospitals in Milan (Italy) involving three respiratory high dependency units and three general wards.Participants Consecutive adult hospitalised patients with a virologically confirmed diagnosis of COVID-19. Patients aged 300 mm Hg).Primary and secondary outcome measures The primary outcome was the assessment of clinical characteristics and in-hospital mortality based on the severity of respiratory failure. Secondary outcomes were intubation rate and application of continuous positive airway pressure during hospital stay.Results 412 patients were enrolled (280 males, 68%). Median (IQR) age was 66 (55–76) years with a PaO2/FiO2 at admission of 262 (140–343) mm Hg. 50.2% had a cardiovascular disease. Prevalence of mild, moderate and severe hARF was 24.4%, 21.9% and 15.5%, respectively. In-hospital mortality proportionally increased with increasing impairment of gas exchange (p

The aim of this essay is to demonstrate how, starting from a continuous reconfiguration of ecological patterns, Homo sapiens has performed a transaction of the architectures that allow him to relate to his own conspecifics and to constantly changing contexts. This transaction, which has been realised in particular by the refinement of his artefacts and by a new understanding of these, creates, in fact, new ontological levels that are destined, in turn, to following transformations. More precisely, the interaction between individual and environment has produced, throughout the evolutionary history of Homo sapiens, a “creative bond” that has remodelled the very concept of living in (and reacting in) the world. The creative evolution that accompanies the history of the modern man is one of the most powerful and versatile types of “grammar”, which paves the way for new task-scapes, redefines boundaries and ways of interaction between “body” and “environment” but, above all, makes the creation of increasingly more user-friendly communicative niches possible today, creating symbolic flows that are increasingly less infused in biological matrices. In other words, the interactional loop between individual and environment creates the cognitive equivalent (Clarck, 2004) of Dawkins’ Extended Phenotype (1982) that, along with a spatial constraint of the physical world, provokes an expansion in the relationship among agents, culture and social networks at the same time.

According to the data derived from several national and international registries, including SANI (Severe Asthma Network Italy), and considering the strong impact that frequent or regular use of oral corticosteroid has on quality of life (QoL) of severe asthmatics, as well as on the costs for managing corticosteroid-related diseases, oral corticosteroid sparing up to withdrawal should be considered a primary outcome in the management of severe asthma. New biologics have clearly demonstrated that this effect is possible, with concomitant reduction in the rate of exacerbations and in symptom control. Then, there is no reason for using so frequently oral corticosteroid before having explored all alternatives currently available for a large part of severe asthmatics.

Background: Non-alcoholic fatty liver disease is the most common cause of liver-related morbidity and mortality in the world. However, no effective pharmacological treatment for this condition has been found.Purpose: This study evaluated the effect of a nutraceutical containing bioactive components from Bergamot citrus and wild cardoon as a treatment for individuals with fatty liver disease. The primary outcome measure was the change in liver fat content.Methods: A total of 102 patients with liver steatosis were enrolled in a double-blind placebo controlled clinical trial. The intervention group received a nutraceutical containing a Bergamot polyphenol fraction and Cynara Cardunculus extract, 300 mg/day for 12 weeks. The control group received a placebo daily. Liver fat content, by transient elastography, serum transaminases, lipids and glucose were measured at the baseline and the end of the study.Results: We found a greater liver fat content reduction in the participants taking the nutraceutical rather than placebo (−48.2 ± 39 vs. −26.9 ± 43 dB/m, p = 0.02); The percentage CAP score reduction was statistically significant in those with android obesity, overweight/obesity as well as in women. However, after adjustment for weight change, the percentage CAP score reduction was statistically significant only in those over 50 years (44 vs. 78% in placebo and nutraceutical, respectively, p = 0.007).Conclusions: This specific nutraceutical containing bioactive components from Bergamot and wild cardoon reduced the liver fat content during 12 weeks in individuals with liver steatosis over 50 years. If confirmed, this nutraceutical could become the cornerstone treatment of patients affected by liver steatosis.Clinical Trial Registration:www.isrctn.com, identifier ISRCTN12833814.

The sanitary survey is aimed at classifying and monitoring the production areas of live bivalve molluscs (LBM) and it is performed using standards that are provided by the Centre for Environment, Fisheries and Aquaculture Science’s Guide to Good Practice. In this study, data from the sanitary survey carried out by the Asl5 Spezzino on the production areas of the gulf of La Spezia during the period 2015-2017 were analysed. The number and type of the analysis performed both on the total sampling and on the individual target species, as well as the number and type of found non-compliance (assessed on both mandatory parameters and on parameters fixed by the local monitoring plan) were considered. Data were also compared with those from the sanitary survey 2012-2014. Appropriate statistic tests were used to evaluate data from E. coli and Norovirus monitoring. Overall, 4306 analysis were performed, especially on the species M. galloprovincialis (89%) and they were mostly focused on to the search of biological agents. 160 NC were detected. Most of the NC concerns the Norovirus’s positivity (93.75%) in M. galloprovincialis and C. gigas. A correlation between the levels of E. coli and rainfall/ seasonality (higher levels in the colder months) was proved, especially in the sampling points located in the inner part of the dam and in the Portovenere Bay. Class B was reconfirmed for M. galloprovincialis, the production areas of C. gigas were reclassified as A and those of V. verrucosa were definitively closed. The sanitary survey was therefore confirmed as a useful tool for reclassification and for monitoring LBM production areas.

This systematic review aims to highlight the differences between different clear aligner therapies that differ in the presence of attachments or in attachment configuration. Eight electronic databases were searched up to March 2020. Two authors independently proceeded to study selection, data extraction, and risk of bias assessment. The analysis of the results was carried out examining six groups of movements (mesio-distal tipping/bodily movement; anterior bucco-lingual tipping/root torque; posterior bucco-lingual tipping/expansion; intrusion; extrusion; rotation). Five clinical trials were selected and all of them showed a medium risk of bias. Literature showed that attachments mostly increase the effectiveness of orthodontic treatment with clear aligners, improving anterior root torque, rotation, and mesio-distal (M-D) movement; they are also important to increase posterior anchorage. However, some articles showed contradictory or not statistically significant results. Attachments also seem to improve intrusion, but the evidence about this movement, as well as extrusion, is lacking. No studies evaluated posterior bucco-lingual tipping/expansion. Further clinical trials are strongly suggested to clarify the influence of attachments and their number, size, shape, and position on each orthodontic movement.

Introduction: Sepsis is one of the most deadly and costly conditions at hospitals. Our study aimed to study levels of knowledge and attitudes in management of sepsis among nurses and physicians employed at Fatebenefratelli hospital, Milano, North-Italy, with particular regard to the analysis of the effects of educational training. Methods: A cross-sectional, quasi-experimental study was conducted between June 1 and October 30, 2017. Physicians and nurses from Intensive Care Unit (ICU) and non-ICU hospital wards were recruited. The study participants were invited to attend some educational workshops and, after 6 months, to fill out a questionnaire based on the 2016 Surviving Sepsis Campaign guidelines. Descriptive statistics were expressed with frequency and percentage (%). Chi-square and Student’s t-test were performed to compare the differences in awareness and knowledge between groups. P-values < 0.05 were considered statistically significant. Results: Nurses and physicians reported both ‘good’ levels (> 75%) of knowledge of procedures that increase risk of sepsis, ‘fairly‘ (50-75%) levels of knowledge, attitudes and behaviour towards blood culture techniques, and ‘poor’ (< 50%) levels of knowledge concerning early identification, methods and scores for diagnosis and management of sepsis. However, with regard to this latter point, T Student test for sample independent confirmed a significant difference in the average percentages of correct answers between recently (~ 6 months) trained (74 ± 3.4%) nurses (n = 33) and physicians (n = 19) and not recently (> 1 years) or never trained (34.8 ± 7.4%) nurses (n = 99) and physicians (n = 30) (t(10) = 11.72, P = < 0.001). Discussion and Conclusion: Our findings showed that levels of knowledge concerning methods and scores for early identification of sepsis can be significantly improved by educational training. A good knowledge of sepsis guidelines is essential to correct management of this condition.

A 52-year-old female, nonalcoholic, with no significant past medical history, was empirically treated with intravenous administration of levofloxacin (LVFX, 750 mg/day) for bronchopneumonia. On day 2, she reported seeing people who are not there (visual hallucinations). She had no history of psychiatric disorders or any family history of mental illness. The patient underwent EEG and brain magnetic resonance imaging (MRI), which resulted normal. Hence, psychiatric and neurological examinations excluded delirium, encephalitis, meningitis, structural neurological lesions. Any endocrine dysfunction (e.g., hypoglyvemia, dyselectrolytemia, diabetic ketoacidosis) or toxic ingestion were also excluded. However, the possibility of levofloxacin-induced acute psychosis was considered and, on day 3, levofloxacin was discontinued with a complete resolution of the patient’s visual hallucinations by her sixth day of hospitalization. The Naranjo Probability Scale (NPS) for determining the likelihood of whether an adverse drug reaction (ADR) is actually due to the drug rather than the result of other factors was calculated as + 6 (‘probable’). In literature, the association between psychiatric adverse events and assumption of fluoroquinolones is known, but only a few cases after assumption of levofloxacin have been reported. However, the true prevalence of levofloxacininduced neuropsychiatric adverse effects could be underestimated. Therefore, physicians and psychiatrists should consider neuropsychiatric adverse effects when prescribing levofloxacin or other fluoroquinolones.

Doxorubicin (Doxo) is a widely used antineoplastic drug which often induces cardiomyopathy, leading to congestive heart failure through the intramyocardial production of reactive oxygen species (ROS). Icariin (Ica) is a flavonoid isolated from Epimedii Herba (Berberidaceae). Some reports on the pharmacological activity of Ica explained its antioxidant and cardioprotective effects. The aim of our study was to assess the protective activities of Ica against Doxo-detrimental effects on rat heart-tissue derived embryonic cardiac myoblasts (H9c2 cells) and to identify, at least in part, the molecular mechanisms involved. Our results showed that pretreatment of H9c2 cells with 1 μM and 5 μM of Ica, prior to Doxo exposure, resulted in an improvement in cell viability, a reduction in ROS generation, the prevention of mitochondrial dysfunction and mPTP opening. Furthermore, for the first time, we identified one feasible molecular mechanism through which Ica could exerts its cardioprotective effects. Indeed, our data showed a significant reduction in Caveolin-1(Cav-1) expression levels and a specific inhibitory effect on phosphodiesterase 5 (PDE5a) activity, improving mitochondrial function compared to Doxo-treated cells. Besides, Ica significantly prevented apoptotic cell death and downregulated the main pro-autophagic marker Beclin-1 and LC3 lipidation rate, restoring physiological levels of activation of the protective autophagic process. These results suggest that Ica might have beneficial cardioprotective effects in attenuating cardiotoxicity in patients requiring anthracycline chemotherapy through the inhibition of oxidative stress and, in particular, through the modulation of Cav-1 expression levels and the involvement of PDE5a activity, thereby leading to cardiac cell survival.

As well known success in orthodontics is related to a correct diagnosis and to a carefull treatment planning. Our study aims to provide clinician with a reproducible and precise method, for orthodontic indirect bonding, thanks to CBCT images and due to a CAD-CAM process. Methods: A case of an orthodontic treatment plan, of a female patient, 37 years old, was selected. Plaster models were digitally acquired using the Extra-Oral scanner Maestro 3D and processed within the Studio Maestro 3D software. CBCT images in DICOM format were imported into the MIMICS software, in order to perform the segmentation of the dental elements, and to obtain a three-dimensional coronal-root dental arches model. The DICOM file thus processed was exported in an STL file, reworked with Meshmixer software to improve image quality, and imported into the 3D Maestro software to be superimposed on the digital model. In this way a three-dimensional real model of the dental arches was developed. After an accurate orthodontic virtual set-up, we proceeded to brackets positioning on the 3D model of the dental arches. Subsequently, a virtual transfer template was created, in order to carry out the digital printing of a thermo-printed mask necessary to perform an indirect bonding of the orthodontic appliance. Results: The original digital workflow proposed in this study allows the development of a real and non-ideal three-dimensional coronal-root model of the dental arches; this model can be used for indirect orthodontic bonding eliminating any errors in the expression of 1st, 2nd and 3rd order information of the pre-informed orthodontic appliance. Conclusions: Technological advancements in oral scanning and 3D printing will allow the achievement of an easy and reproducible ideal positioning of the orthodontic brackets. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of death globally, associated with multifactorial pathophysiological components. In particular, genetic mutations, infection or inflammation, unhealthy eating habits, exposition to radiation, work stress, and/or intake of toxins have been found to contribute to the development and progression of cancer disease states. Early detection of cancer and proper treatment have been found to enhance the chances of survival and healing, but the side effects of anticancer drugs still produce detrimental responses that counteract the benefits of treatment in terms of hospitalization and survival. Recently, several natural bioactive compounds were found to possess anticancer properties, capable of killing transformed or cancerous cells without being toxic to their normal counterparts. This effect occurs when natural products are associated with conventional treatments, thereby suggesting that nutraceutical supplementation may contribute to successful anticancer therapy. This review aims to discuss the current literature on four natural bioactive extracts mostly characterized by a specific polyphenolic profile. In particular, several activities have been reported to contribute to nutraceutical support in anticancer treatment: (1) inhibition of cell proliferation, (2) antioxidant activity, and (3) anti-inflammatory activity. On the other hand, owing to their attenuation of the toxic effect of current anticancer therapies, natural antioxidants may contribute to improving the compliance of patients undergoing anticancer treatment. Thus, nutraceutical supplementation, along with current anticancer drug treatment, may be considered for better responses and compliance in patients with cancer. It should be noted, however, that when data from studies with bioactive plant preparations are discussed, it is appropriate to ensure that experiments have been conducted in accordance with accepted pharmacological research practices so as not to disclose information that is only partially correct.

Background: Restrictions due to the COVID-19 pandemic limited patients’ access to hospital care. The aims of this study were to assess dietary nutritional status, quality of life (QoL), and adherence to dietary therapy before and after 30-day personalized diet therapy through telenutrition tools in patients with systemic nickel allergic syndrome (SNAS). Methods: Each SNAS patient underwent the following allergological procedures: (a) face-to-face visit (nutritional visit and QoL evaluation) with prescription of one out of five personalized and balanced dietary plans different for calorie intake, (b) video call visit for dietary evaluation and assessment of adherence to diet after 15 days, and (c) video call visit for dietary and QoL evaluation and assessment of adherence to diet therapy after 30 days (end of study). Results: We enrolled 20 SNAS patients. After 15 and 30 days, we found a statistically significant improvement in anthropometric findings after diet therapy, a significant adherence rate to low-nickel diet (60% and 80%, respectively), and an improvement in QoL with an increase in almost all psychometric indices. Conclusions: Our study demonstrates that telenutrition can be a valid tool to monitor nutritional status and adherence to balanced low-Ni diet positively affecting QoL in SNAS patients during the COVID-19 pandemic.

Cardiovascular disease is the leading cause of death and disability in the Western world. In order to safeguard the structure and the functionality of the myocardium, it is extremely important to adequately support the cardiomyocytes. Two cellular organelles of cardiomyocytes are essential for cell survival and to ensure proper functioning of the myocardium: mitochondria and the sarcoplasmic reticulum. Mitochondria are responsible for the energy metabolism of the myocardium, and regulate the processes that can lead to cell death. The sarcoplasmic reticulum preserves the physiological concentration of the calcium ion, and triggers processes to protect the structural and functional integrity of the proteins. The alterations of these organelles can damage myocardial functioning. A proper nutritional balance regarding the intake of macronutrients and micronutrients leads to a significant improvement in the symptoms and consequences of heart disease. In particular, the Mediterranean diet, characterized by a high consumption of plant-based foods, small quantities of red meat, and high quantities of olive oil, reduces and improves the pathological condition of patients with heart failure. In addition, nutritional support and nutraceutical supplementation in patients who develop heart failure can contribute to the protection of the failing myocardium. Since polyphenols have numerous beneficial properties, including anti-inflammatory and antioxidant properties, this review gathers what is known about the beneficial effects of polyphenol-rich bergamot fruit on the cardiovascular system. In particular, the role of bergamot polyphenols in mitochondrial and sarcoplasmic dysfunctions in diabetic cardiomyopathy is reported.

In recent decades, interest in natural compounds has increased exponentially due to their numerous beneficial properties in the treatment of various acute and chronic diseases. A group of plant derivatives with great scientific interest is terpenic compounds. Among the plants richest in terpenes, the genus Ferula L. is one of the most representative, and ferutinin, the most common sesquiterpene, is extracted from the leaves, rhizome, and roots of this plant. As reported in the scientific literature, ferutinin possesses antioxidant and anti-inflammatory properties, as well as valuable estrogenic properties. Neurodegenerative and demyelinating diseases are devastating conditions for which a definite cure has not yet been established. The mechanisms involved in these diseases are still poorly understood, and oxidative stress is considered to be both a key modulator and a common denominator. In the proposed experimental system, co-cultured human neurons (SH-SY5Y) and human oligodendrocytes (MO3.13) were treated with the pro-inflammatory agent lipopolysaccharide at a concentration of 1 μg/mL for 24 h or pretreated with ferutinin (33 nM) for 24 h and subsequently exposed to lipopolysaccharide 1 μg/mL for 24 h. Further studies would, however, be needed to establish whether this natural compound can be used as a support strategy in pathologies characterized by progressive inflammation and oxidative stress phenomena.

Doxorubicin is an anthracycline that is commonly used as a chemotherapy drug due to its cytotoxic effects. The clinical use of doxorubicin is limited due to its known cardiotoxic effects. Treatment with anthracyclines causes heart failure in 15–17% of patients, resulting in mitochondrial dysfunction, the accumulation of reactive oxygen species, intracellular calcium dysregulation, the deterioration of the cardiomyocyte structure, and apoptotic cell death. Polyphenols have a wide range of beneficial properties, and particular importance is given to Bergamot Polyphenolic Fraction; Oleuropein, one of the main polyphenolic compounds of olive oil; and Cynara cardunculus extract. These natural compounds have particular beneficial characteristics, owing to their high polyphenol contents. Among these, their antioxidant and antoproliferative properties are the most important. The aim of this paper was to investigate the effects of these three plant derivatives using an in vitro model of cardiotoxicity induced by the treatment of rat embryonic cardiomyoblasts (H9c2) with doxorubicin. The biological mechanisms involved and the crosstalk existing between the mitochondria and the endoplasmic reticulum were examined. Bergamot Polyphenolic Fraction, Oleuropein, and Cynara cardunculus extract were able to decrease the damage induced by exposure to doxorubicin. In particular, these natural compounds were found to reduce cell mortality and oxidative damage, increase the lipid content, and decrease the concentration of calcium ions that escaped from the endoplasmic reticulum. In addition, the direct involvement of this cellular organelle was demonstrated by silencing the ATF6 arm of the Unfolded Protein Response, which was activated after treatment with doxorubicin.

The patient was an 80-year-old man who arrived at the emergency room with breathing problems. He presented a history of chronic obstructive pulmonary disease (COPD), hypertension, diabetes mellitus and early (stage 1) chronic renal failure with normal levels of creatinine and no sign and symptoms of renal disease. A chest X-ray showed pneumonia. Therefore, he was first treated with 1 g daily of ceftriaxone IV. We did not observe any clinical improvement, and for this reason, a sputum culture was performed to guide the right antibiotic treatment. Subsequently, we started a new antibiotic therapy with trimethoprim/sulfamethoxazole (TMP/SMX) adjusted to renal functioning. Appropriate medical treatment was administered, as well as urine alkalinisation. After the first day of treatment, the patient’s clinical and laboratory status worsened very quickly, with an increased level of serum creatinine from 1.5 to 3.5 mg/dL. We stopped administering the antibiotic therapy immediately. However, we observed acute renal failure with a serum creatinine level of 9.0 mg/dL and four days after his admission, the patient died. Literature showed that patients can develop acute kidney injury (AKI) during or immediately following TMP/SMX therapy. Intrinsic renal impairment –rather, interstitial nephritis– appeared responsible for the great majority of cases, and impairment was transient if therapy was discontinued. In our study, despite the therapy with TMP/SMX was immediately discontinued, and our patient underwent appropriate medical treatment, urine alkalinisation and, then, haemodialysis, the AKI was rapidly fatal. In conclusion, particular attention should be paid to prescribing TMP/SMX to patients affected by chronic renal failure.

Abstract Background Scientific evidence showed that rapid maxillary expansion (RME) affects naso-maxillary complex, increasing nasal width and volume. This study aimed to evaluate nasal changes induced by rapid maxillary expansion with different anchorage and appliance design by using low dose and cone beam computed tomography. Methods A total of 44 patients (20 males, mean age 8y 8 m ± 1y 2 m; 24 females mean age 8y 2 m ± 1y 4 m) were included in the investigation and divided into three groups according to the appliance: Hyrax-type expander anchored to permanent teeth, modified Hyrax-type expander anchored to deciduous teeth, modified Haas-type expander anchored to deciduous teeth. Maxillary expansion was performed until overcorrection and the expander was passively kept in situ for 7 months at least. All patients had three-dimensional imaging before expansion (T0) and after the retention period (T1). Nasal floor width, nasal wall width, maxillary inter-molar width were measured by means of Mimics software. The paired sample t-test was employed to assess the significance of the differences between the time points; the analysis of variance test (ANOVA) was used to compare differences between groups. Results The statistical analysis revealed significant differences between T0 and T1 for each recorded measurement in each group; no significant differences were found by comparing groups. Conclusions Rapid maxillary expansion produces a significant skeletal transverse expansion of nasal region in growing patients. No significant differences in nasal effects are expected when the appliance is anchored onto deciduous teeth, with or without the palatal acrylic coverage.

Abstract Background The aim of this study is to identify cephalometric pretreatment parameters for prediction of Class II improvement induced by rapid maxillary expansion. Methods Lateral cephalograms of 30 patients (mean age 8.3 ± 1.6 years old) showing Class II molar relationship and undergone to rapid maxillary expansion on the upper deciduous molars were traced before treatment, and molar relation changes were evaluated on dental casts before and after treatment. Overall treatment time lasted 10.2 ± 2 months. Good responders (18 subjects, 10 females and 8 males) showed improvement of at least 2.50 mm, and bad responders (12 subjects, 7 females and 5 males) showed no improvement, improvement less than 2.50 mm, or worsening of molar relationship after treatment. Student’s t test was used to assess significance of differences between groups, and discriminant analysis allowed identification of predictive pretreatment variables. Results Articular angle, superior gonial angle, and mandibular dimensions (Co-Gn, S-Ar, Ar-Go, Go-Me) showed significant differences in the comparison between groups. Mandibular length Co-Gn and superior gonial angle were selected as significant predictive variable for discrimination. Conclusions Patients with smaller mandibular length and more acute superior gonial angle are expected to have more chances to improve molar Class II after rapid maxillary expansion.

In the literature, hypothyroidism-induced hyponatraemia is rare and probably occurs only in severe hypothyroidism characterised by myxoedema. An 82-year-old woman arrived at an emergency department with aphasia and a progressive cognitive impairment associated with walking problems during the last week. Examinations excluded neurological disease. The diagnosis showed a clinically relevant association between hyponatraemia and hypothyroidism disorder characterised by neurological symptoms. In conclusion, this could be one of the few cases, to our knowledge, of non-severe hypothyroidism-induced hyponatraemia.

The introduction of ultra-precision targeted therapy has become a significant advancement in cancer therapeutics by creating treatments with less off target effects. Specifically with papillary thyroid carcinoma (PTC), the cancer's hallmark genetic mutation BRAFV600E can be targeted with selective inhibitors, such as vemurafenib. Despite initial positive tumor responses of regression and decreased viability, both single agent or combination agent drug treatments provide a selective pressure for drug resistant evolving clones within the overall heterogeneous tumor. Also, there are evidences suggesting that sequential monotherapy is ineffective and selects for resistant and ultimately lethal tumor clones. Reconstructing both clonal and subclonal thyroid tumor heterogeneous cell clusters for somatic mutations and epigenetic profile, copy number variation, cytogenetic alterations, and non-coding RNA expression becomes increasingly critical as different clonal enrichments implicate how the tumor may respond to drug treatment and dictate its invasive, metastatic, and progressive abilities, and predict prognosis. Therefore, development of novel preclinical and clinical empirical models supported by mathematical assessment will be the tools required for estimating the parameters of clonal and subclonal evolution, and unraveling the dormant vs. non-dormant state of thyroid cancer. In sum, novel experimental models performing the reconstruction both pre- and post-drug treatment of the thyroid tumor will enhance our understanding of clonal and sub-clonal reconstruction and tumor evolution exposed to treatments during ultra-precision targeted therapies. This approach will improve drug development strategies in thyroid oncology and identification of disease-specific biomarkers.

Thyroid cancer (TC) is the most common endocrine malignancy. Most TCs have a favorable prognosis, whereas anaplastic thyroid carcinoma (ATC) is a lethal form of cancer. Different genetic and epigenetic alterations have been identified in aggressive forms of TC such as ATC. Non-coding RNAs (ncRNAs) represent functional regulatory molecules that control chromatin reprogramming, including transcriptional and post-transcriptional mechanisms. Intriguingly, they also play an important role as coordinators of complex gene regulatory networks (GRNs) in cancer. GRN analysis can model molecular regulation in different species. Neural networks are robust computing systems for learning and modeling the dynamics or dependencies between genes, and are used for the reconstruction of large data sets. Canonical network motifs are coordinated by ncRNAs through gene production from each transcript as well as through the generation of a single transcript that gives rise to multiple functional products by post-transcriptional modifications. In non-canonical network motifs, ncRNAs interact through binding to proteins and/or protein complexes and regulate their functions. This article overviews the potential role of ncRNAs GRNs in TC. It also suggests prospective applications of deep neural network analysis to predict ncRNA molecular language for early detection and to determine the prognosis of TC. Validation of these analyses may help in the design of more effective and precise targeted therapies against aggressive TC.

Atherothrombosis, a multifactorial and multistep artery disorder, represents one of the main causes of morbidity and mortality worldwide. The development and progression of atherothrombosis is closely associated with age, gender and a complex relationship between unhealthy lifestyle habits and several genetic risk factors. The imbalance between oxidative stress and antioxidant defenses is the main biological event leading to the development of a pro-oxidant phenotype, triggering cellular and molecular mechanisms associated with the atherothrombotic process. The pathogenesis of atherosclerosis and its late thrombotic complications involve multiple cellular events such as inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells (SMCs), extracellular matrix (ECM) alterations, and platelet activation, contributing to chronic pathological remodeling of the vascular wall, atheromatous plague formation, vascular stenosis, and eventually, thrombus growth and propagation. Emerging studies suggest that clotting activation and endothelial cell (EC) dysfunction play key roles in the pathogenesis of atherothrombosis. Furthermore, a growing body of evidence indicates that defective autophagy is closely linked to the overproduction of reactive oxygen species (ROS) which, in turn, are involved in the development and progression of atherosclerotic disease. This topic represents a large field of study aimed at identifying new potential therapeutic targets. In this review, we focus on the major role played by the autophagic pathway induced by oxidative stress in the modulation of EC dysfunction as a background to understand its potential role in the development of atherothrombosis.

Background: Panoramic radiography creates distortion in teeth position and inclination especially in lateral areas of the arches due to acquisition and curved shape of dental arch. The aim of this study was to evaluate panoramic distortion compared to cone-beam computed tomography. Methods: Mesiodistal angulations were measured on panoramic radiography. Mesiodistal angulations and buccolingual inclinations of the teeth were determined on cone-beam computed tomography scans. The previous measurements were then compared through Pearson correlation coefficient. Results: The results showed higher correlation between mesiodistal 2D angulation and buccolingual 3D inclination, especially for first premolars, rather than between mesiodistal angulations measured in 2D and 3D. Conclusion: Especially for the lateral areas of the dental arches, root mesiodistal angulation measured on panoramic radiography is not reliable; in fact, it is greatly influenced by buccolingual inclination. Therefore, clinical evaluation is highly recommended with panoramic radiography to provide correct diagnosis and the most satisfactory results.

The high incidence of obesity is associated with an increasing risk of several chronic diseases such as cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Sustained obesity is characterized by a chronic and unsolved inflammation of adipose tissue, which leads to a greater expression of proinflammatory adipokines, excessive lipid storage and adipogenesis. The purpose of this review is to clarify how inflammatory mediators act during adipose tissue dysfunction in the development of insulin resistance and all obesity-associated diseases. In particular, we focused our attention on the role of inflammatory signaling in brown adipose tissue (BAT) thermogenic activity and the browning of white adipose tissue (WAT), which represent a relevant component of adipose alterations during obesity. Furthermore, we reported the most recent evidence in the literature on nutraceutical supplementation in the management of the adipose inflammatory state, and in particular on their potential effect on common inflammatory mediators and pathways, responsible for WAT and BAT dysfunction. Although further research is needed to demonstrate that targeting pro-inflammatory mediators improves adipose tissue dysfunction and activates thermogenesis in BAT and WAT browning during obesity, polyphenols supplementation could represent an innovative therapeutic strategy to prevent progression of obesity and obesity-related metabolic diseases.

Cardiovascular diseases (CVDs), which include congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, and many other cardiac disorders, cause about 30% of deaths globally; representing one of the main health problems worldwide. Among CVDs, ischemic heart diseases (IHDs) are one of the major causes of morbidity and mortality in the world. The onset of IHDs is essentially due to an unbalance between the metabolic demands of the myocardium and its supply of oxygen and nutrients, coupled with a low regenerative capacity of the heart, which leads to great cardiomyocyte (CM) loss; promoting heart failure (HF) and myocardial infarction (MI). To date, the first strategy recommended to avoid IHDs is prevention in order to reduce the underlying risk factors. In the management of IHDs, traditional therapeutic options are widely used to improve symptoms, attenuate adverse cardiac remodeling, and reduce early mortality rate. However, there are no available treatments that aim to improve cardiac performance by replacing the irreversible damaged cardiomyocytes (CMs). Currently, heart transplantation is the only treatment being carried out for irreversibly damaged CMs. Hence, the discovery of new therapeutic options seems to be necessary. Interestingly, recent experimental evidence suggests that regenerative stem cell medicine could be a useful therapeutic approach to counteract cardiac damage and promote tissue regeneration. To this end, researchers are tasked with answering one main question: how can myocardial regeneration be stimulated? In this regard, natural compounds from plant extracts seem to play a particularly promising role. The present review will summarize the recent advances in our knowledge of stem cell therapy in the management of CVDs; focusing on the main properties and potential mechanisms of natural compounds in stimulating and activating stem cells for myocardial regeneration.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection is associated, alongside with lung infection and respiratory disease, to cardiovascular dysfunction that occurs at any stage of the disease. This includes ischemic heart disease, arrhythmias, and cardiomyopathies. The common pathophysiological link between SARS-CoV-2 infection and the cardiovascular events is represented by coagulation abnormalities and disruption of factors released by endothelial cells, which contribute in maintaining the blood vessels into an anti-thrombotic state. Thus, early alteration of the functionality of endothelial cells, which may be found soon after SARS-CoV-2 infection, seems to represent the major target of a SARS CoV-2 disease state and accounts for the systemic vascular dysfunction that leads to a detrimental effect in terms of hospitalization and death accompanying the disease. In particular, the molecular interaction of SARS-CoV-2 with the ACE2 receptor located in the endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function, which, in turn, is followed by vascular inflammation and thrombosis of peripheral blood vessels. This highlights systemic hypoxia and further aggravates the vicious circle that compromises the development of the disease, leading to irreversible tissue damage and death of people with SARS CoV-2 infection. The review aims to assess some recent advances to define the crucial role of endothelial dysfunction in the pathogenesis of vascular complications accompanying SARS-CoV-2 infection. In particular, the molecular mechanisms associated with the interaction of SARS CoV-2 with the ACE2 receptor located on the endothelial cells are highlighted to support its role in compromising endothelial cell functionality. Finally, the consequences of endothelial dysfunction in enhancing pro-inflammatory and pro-thrombotic effects of SARS-CoV-2 infection are assessed in order to identify early therapeutic interventions able to reduce the impact of the disease in high-risk patients.

The employment studies of natural extracts in the prevention and treatment of several diseases highlighted the role of different species of genus Ferula L., belonging to the Apiaceae family, dicotyledonous plants present in many temperate zones of our planet. Ferula communis L. is the main source of sesquiterpene ferutinin, a bioactive compound studied both in vitro and in vivo, because of different effects, such as phytoestrogenic, antioxidant, anti-inflammatory, but also antiproliferative and cytotoxic activity, performed in a dose-dependent and cell-dependent way. The present review will focus on the molecular mechanisms involved in the different activities of Ferutinin, starting from its antioxidant potential at low doses until its ionophoric property and the subsequent mitochondrial dysfunction induced through administration of high doses, which represent the key point of its anticancer action. Furthermore, we will summarize the data acquired from some experimental studies on different cell types and on several diseases. The results obtained showed an important antioxidant and phytoestrogenic regulation with lack of typical side effects related to estrogenic therapy. The preferential cell death induction for tumor cell lines suggests that ferutinin may have anti-neoplastic properties, and may be used as an antiproliferative and cytotoxic agent in an estrogen dependent and independent manner. Nevertheless, more data are needed to clearly understand the effect of ferutinin in animals before using it as a phytoestrogen or anticancer drug.

Background: The basophil activation test (BAT) is used to improve the accuracy of food allergy diagnosis. To date, the influence of antiallergic drugs on BAT reactivity is poorly investigated. The aim of the study was to investigate if BAT results were influenced by antihistamine intake for 3 months in a cohort of patients with IgE-mediated food allergy to milk or egg. Methods: A retrospective, single-center, observational study was performed. We enrolled subjects with history of hypersensitivity reaction after specific food ingestion, positive skin prick tests and specific IgEs, concomitant allergic rhinitis, and, contraindication to the double-blind, placebo-controlled food challenge due to personal history of systemic reactions related to the ingestion of culprit food. Validated allergens (α-lactoalbumin, β-lactoglobulin, casein, egg white, and yolk) for BAT were used. Results: Thirty-nine patients with well-documented food symptoms and positive allergological workup were included in the study. BAT was positive in 29 patients. The mean percentages of CD63+ expression to specific culprit allergen did not change after the administration of drugs. Conclusions: This was the first study assessing the effects of oral antihistamines on basophil reactivity in cow’s milk and egg food allergy. Antihistamines do not interfere with BAT results.

Today, the attention to food security has grown with the awareness of resources’ scarcity, earth excessive exploitation, population growth and climate change, all factors that are associated with an impelling food emergency. A plethora of theoretical perspectives adopted in analysing food security issue reflects in diverse normative approaches. Some focus on the rapport between population demand and food supply, seeking to reduce the former or increase the latter in order to achieve food security. Applying the technological progress of scientific research will have its positive outcomes: production will increase, keeping prices low; the limited resources will be used more efficiently, decreasing the consumption of water, energy and land; the environment will benefit from a more sustainable production. However, scientific solutions, such as population control, that do not restore individuals’ entitlement to food will be ineffective in preventing food insecurity. Therefore, food security it is not achievable by the sole means of science. A greater quantity of food does not guarantee a more equal distribution of resources. Increasing food production without altering its uneven distribution will only augment this inequality, making who has access to food more secure but not helping who is currently affected by the food insecurity issues. Science can play its role, but development towards the solutions to food insecurity must be led by politics.

Introduction. A mass gathering (MG) is when a large number of people come together in a particular location for a specific purpose. Expo 2015 was an universal exposition hosted by Milan, Italy. The Pre-Hospital Emergency Company (AREU) of Lombardy Region (Milan-Italy) was involved in planning and managing the emergency rescue response inside the Expo 2015 area in Milan. In this paper, we review the AREU medical and public health response for the 2015 Milan Expo. Methods. Existing risk-assessment processes for MGs were used (the Arbon Predictive Score and Maurer Score) to define the expected resources and the impact on the health systems. The objective of the plan was to reduce the impact of the event by adopting the model of First Aid Points (advanced medical posts) deployed in the event site acting as ‘first health filters’ for the hospital network in Milan. Results. Our data indicate that 13,579 visitors were rescued in the ‘Red Area’ from 1 May to 31 October (with an average of 73 cases per day); 9,501 of them needed initial treatment or observation time at the First Aid Points, 1,289 of them were hospitalised (1% Red code, 29% Yellow code, 70% Green code); 65% of patients (57% female, with a mean age of 37 years old) had medical problems. Fatigue, light- headedness, dizziness, syncope, loss of consciousness and headache were the prevalent medical diagnoses. Conclusions. Our study confirms that environmental factors, such as the weather, can contribute to large numbers of ill people at MGs. Overall, the AREU of Lombardy Region demonstrated excellent preparation for the Expo 2015 MG. Flexibility, integration and strong cooperation between the pre-hospital settings and hospitals were incorporated into the application of the plan. The final data showed the effectiveness of the adopted model and the reduced impact on the hospital network.

We report the case of a 40-year-old woman presenting during the night to the emergency department for thoracic pain and pain in the upper arm. An electrocardiogram (ECG) showed diffuse ST segment elevation. A coronarography (CVG) showed spontaneous dissection of the interventricular anterior artery. Many patients present with chest pain to emergency departments (ED). Spontaneous coronary artery dissection (SCAD) should be considered in any young patient, especially young women, without a history of coronary heart disease or risk factors, who presents with an acute myocardial infarction or cardiac arrest.

Background: The upgoing thumb sign has been frequently observed in patients with minor strokes and transient ischemic attacks as an indicator of brain involvement. We assessed the effect of primary motor cortex (M1) inhibition in the development of the upgoing thumb sign. Methods: Used repetitive Transcranial Magnetic Stimulation (rTMS, 1Hz frequency for 15min, 1s ISI, 900 pulses) at 60% of resting motor threshold to inhibit the right or left primary motor cortex of 10 healthy individuals. Participants were examined before and after rTMS by a neurologist who was blind to the site of motor cortex inhibition. Results: 10 neurological intact participants (5 women/5 men) were recruited for this study. 2 cases were excluded due to pre-existing possible thumb signs. After the inhibition of the primary motor cortex, in 6 subjects out of 8, we observed a thumb sign contralateral to the site of primary motor cortex inhibition. In one subject an ipsilateral thumbs sign was noted. In another case, we did not find an upgoing thumb sign. Conclusion: The upgoing thumb sign is a subtle neurological finding that may be related to the primary motor cortex or corticospinal pathways involvements. Keywords: Corticospinal tract, Upper motor neuron lesions, Primary motor cortex, Transcranial magnetic stimulation