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Abstract Background Nutraceuticals represent a new therapeutic frontier in the treatment of metabolic syndrom (MetS) and related cardiovascular risk factors. The aim of this study was to evaluate the potential beneficial effects of Armolipid Plus (AP) (berberine 500 mg, red yest rice, monacolin K 3 mg and policosanol 10 mg) on insulin resistance, lipid profile, particularly on small and dense LDL cholesterol (sdLDL-C), representing the most atherogenic components, as well as its effects on high sensitivity C-reactive protein, a notable marker of cardiovascular risk, blood pressure and cardiac remodeling in subjects affected by MetS, with left ventricular hypertrophy. Methods The study was a prospective, multi-center, randomized, double blind, placebo-controlled trial. One hundred and fifty eight patients, aged between 28 and 76 years old, were enrolled and randomized to receive either one tablet of AP or placebo (PL) once daily for 24 weeks. Anthropometric and vital parameters, total cholesterol (tot-C), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceridemia (TG), non-HDL cholesterol (NHDL-C) and sdLDL-C were evaluated. Results After 24 weeks of treatment, the analysis performed on 141 subjects (71 in AP arm and 70 in PL arm), showed a significant improvement of lipid profile in the AP group, with reduction in tot-C (− 13.2 mg/dl), LDL-C (− 13.9 mg/dl) and NHDL-C (− 15.3 mg/dl) and increase in HDL-C (+ 2.0 mg/dl). These changes were equally significant compared with placebo (tot-C: AP − 13.2 mg/dL vs PL + 2.7 mg/dL, p

[This corrects the article DOI: 10.1371/journal.pone.0221683.].

The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease and may be a treatment for NASH due to its antioxidant properties. We aimed to assess the safety and efficacy of higher than customary doses of silymarin in non-cirrhotic patients with NASH. This exploratory randomized double-blind placebo controlled multicenter Phase II trial tested a proprietary standardized silymarin preparation (Legalon®, Rottapharm|Madaus, Mylan) and was conducted at 5 medical centers in the United States. Eligible adult patients had liver biopsy within 12 months showing NASH without cirrhosis with NAFLD Activity Score (NAS) ≥4 per site pathologist's assessment. Participants were randomized to Legalon® 420 mg, 700 mg, or placebo t.i.d. for 48 weeks. The primary endpoint was histological improvement ≥2 points in NAS. Of 116 patients screened, 78 were randomized. There were no significant differences in adverse events among the treatment groups. After 48-50 weeks, 4/27 (15%) in the 700 mg dose, 5/26 (19%) participants randomized to 420 mg, and 3/25 (12%) of placebo recipients reached the primary endpoint (p = 0.79) among all randomized participants, indicating no benefit from silymarin in the intention to treat analysis Review by a central pathologist demonstrated that a substantial number of participants (49, 63%) did not meet histological entry criteria and that fibrosis stage improved most in the placebo treated group, although not significantly different from other groups. Silymarin (Legalon®) at the higher than customary doses tested in this study is safe and well tolerated. The effect of silymarin in patients with NASH remains inconclusive due to the substantial number of patients who entered the study but did not meet entry histological criteria, the lack of a statistically significant improvement in NAS of silymarin treated patients, and the unanticipated effect of placebo on fibrosis indicate the need for additional clinical trials. Trial Registration: clinicaltrials.gov, Identifier: NCT00680407.

Abstract Background Human papillomavirus (HPV) infection is a leading cause of oropharyngeal squamous cell cancer (OPSCC). This study aimed to carry out a Knowledge, Attitude and Perception survey on HPV infection, HPV+ OPSCC, and HPV vaccination among Italian dental students. Methods Through an online self-administered questionnaire consisting of 82 questions, data on dental students’ sociodemographic characteristics, knowledge, attitudes and perceptions concerning HPV+ OPSCC, infection and vaccination were acquired. A statistical analysis, based on their year of attendance (early career, from 1st to 3rd year vs. late career, from 4th to 6th year) was also conducted. Results A total of 412 dental students completed the questionnaire. Knowledge of HPV+ OPSCC was reported by 61% of early-career students and 73% of late-career students, with high awareness of the HPV-OPSCC correlation in both groups (85% vs. 89%, respectively). The percentage of correct responses regarding HPV infection knowledge was 61% for early-career and 73% for late-career students, while vaccine knowledge was 70% and 78%, respectively. Over 90% of students acknowledged the dentist’s role in educating patients about HPV and OPSCC, and attitudes toward discussing HPV and vaccination were positive. However, only about half would recommend the vaccine to either gender. Statistically significant differences were found between early- and late-career groups across all knowledge sections (p

ObjectivesThe goal of the study was to analyze the eruption time of the maxillary impacted canines treated with the “canine first technique” and evaluate the success rate.Materials and methodsA total of 103 patients with 131 impacted canines were treated. Alpha angle, Erickson–Kurol sectors, and age were studied to assess the difficulty of canine eruption. All the canines were treated with the “canine first” approach. The median follow-up time was evaluated using the Kaplan–Meier inverse procedure. The primary outcome (canine eruption time) was analyzed using Kaplan–Meier curves. The curve comparison between the different known risk factors was made using the log-rank test. The median eruption time (95% confidence interval) was calculated for each result.ResultsThe majority of the canines (66.4%) were placed palatally and positioned in sector 3 (30.16%). The median alpha angle was 38.7°. In 88.9% of cases, canines erupted and the median time of eruption was 4.2 months. A statistically significant difference in alpha angle >//

A prosthetic rehabilitation, whether supported by implants, teeth, or mucous membranes, must be functionally and aesthetically adequate, so it is essential that the oral structures are reproduced as accurately as possible. The purpose of this overview is to evaluate the accuracy, time of digital impressions, and patient preference compared to those of conventional high-precision in vivo impressions. This umbrella review was developed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement and was registered in the PROSPERO systematic review registry. The search method and study selection were based on the PEO (Population–Exposure–Outcome) model, a modified version of the PICO model. Systematic reviews regarding the dental impression technique made using an intraoral scanner versus the analog impression technique made with high-precision impression materials were searched electronically up to 1 February 2023 among articles published in English, through numerous registries and databases, such as PROSPERO e, Scopus, MEDLINE/ PubMed, BioMed Central, and Cochrane Library. The records screened totaled 2942, but only 23 systematic reviews were included in this umbrella review. The Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool was used to evaluate the quality assessment of the systematic reviews included in this umbrella review. Accuracy, time, and patient preference for digital impressions were compared with those of high-precision conventional impressions. A total of 23 systematic reviews were included in this umbrella review. From the analysis of this umbrella review, the data on the accuracy between the two methods of taking the impression are conflicting, especially as regards full-arch rehabilitations. However, the digital impression seems to be preferred over the analog one as regards time and patient preference. However, there is limited high-quality evidence available for studying conventional and digital implant impressions. The results obtained are limited to the type of review performed, and the type of studies included was limited by the settings and study designs. Furthermore, another important limitation highlighted was that the digital scanners analyzed in the various studies are not the same, and the number of missing teeth or implants inserted is not the same. More in vivo clinical studies and RCTs are needed to increase the level of evidence for impression procedures.

This paper proposes the establishment of a European Debt Agency (EDA) as a tool for the efficient management of Eurozone public debt, to address two primary risks: roll-over and sustainability risk. The proposed EDA would price its loans using a transparent formula that would anchor the price to fundamental economic factors. This approach would encourage fiscal discipline among Member States and avoid inefficient costs resulting from market price deviations from fundamentals, without resorting to debt mutualization. In addition, the paper suggests that adopting flexible fiscal rules alongside the EDA could result in a smoother path towards debt stabilization, by mitigating the macroeconomic effects of excessive fluctuations in risk premia. The simulations indicate that this combination could offer a comprehensive strategy for managing sovereign debt in the Eurozone that would promote fiscal responsibility and stability.

Although rare, oral manifestations of hypersensitivity reactions in orthodontic patients pose a significant clinical challenge due to their heterogeneous presentations, and can cause discomfort and pain, possibly impacting patients’ quality of life and orthodontic treatment duration and outcomes. This comprehensive review aimed to elucidate the oral, perioral, and systemic manifestations of hypersensitivity reactions in orthodontic subjects, focusing on patients with fixed appliances, removable appliances, and clear aligners, and detailing their epidemiology, macroscopic and microscopic features, allergy testing, clinical implications, and specific management strategies. Oral and extra-oral manifestations of (immediate and delayed) hypersensitivity reactions occur rarely and are due to the release of metal and non-metal ions from orthodontic appliances. They typically present as erythema, erosive–ulcerative lesions, and gingival hyperplasia, with histopathological findings showing inflammatory infiltrates. Nickel is a significant allergen, and diagnostic tests like patch tests are essential for managing these reactions. Likely due to prolonged contact with oral tissues, fixed orthodontic appliances pose a higher risk compared to removable appliances and clear aligners. Early identification and removal of allergenic materials, combined with effective treatments, can resolve symptoms and prevent recurrence. Keeping dental and medical records updated and knowing family and personal medical histories helps clinicians choose appropriate materials and counsel patients about potential risks. Proper patient education, regular monitoring, and using hypoallergenic materials are key strategies for managing these reactions.

Patients hospitalized with COVID-19 pneumonia are at risk for thrombotic complications. At the same time, they need respiratory support, and they frequently require nursing in a prone position. From March to May 2020, 57 patients with acute respiratory distress syndrome were admitted to our departments. Our therapeutic protocol included anticoagulant treatment and prone positioning. We have treated three obese women affected by severe pneumonia and pectoral hematoma with post-hemorrhagic anemia. We have already described two of these cases in our previous publication; in this new article, we describe a third similar case and review clinical reports from 2020 to 2022 about hemorrhagic complications during COVID-19. Reports confirm that pectoral hematomas and bleeding in unusual sites are a complication of COVID-19. Pectoral hematomas are likely to be related to COVID-19 severity, heparin dosage, and traumatism due to cough and pronosupination.

Psoriasis is a widespread chronic inflammatory skin disease, that negatively affects physical and emotional well-being and quality of life, as shown by the generally low Dermatology Life Quality Index (DLQI). Psoriasis is burdened by associated comorbidities and some patients manifest concurrent oral lesions, although the existence of oral psoriasis remains controversial. Psoriasis-specific and nonspecific oral lesions and Oral Health-Related Quality of Life (OHRQoL), self-assessed using the Oral Health Impact Profile-14 (OHIP-14) questionnaire, were retrospectively reviewed in adult untreated psoriasis patients with ≥15 teeth, who were non-smokers and had no dental or periodontal infections. Sample (age, gender, comorbidities) and descriptive variables (Body Surface Area-BSA, Psoriasis Area and Severity Index-PASI, Dermatology Life Quality Index-DLQI, severity of psoriasis, distribution of lesions and predominant involvement, years since diagnosis) were correlated with DLQI and OHIP-14 and compared by baseline DLQI and OHRQoL classes. Charts from 90 participants were included. No oral lesions were detected, and excellent/good OHRQoL was found in 94% of the participants. DLQI scores displayed positive significant associations with PASI and BSA, while OHIP-14 with hypertension and IMID, and age. PASI and BSA were significantly higher in participants with DLQI > 10 and also differed significantly among OHQRoL ranks, as well as mucosal involvement and comorbidities. Specifically, among subjects revealing an Excellent OHQRoL, 92.6% were non-IMID, 75% non-hypertensive, 89.7% non-diabetic subjects, 86.8% of non CVD-subjects.

Root canal treatment represents a significant challenge as current cleaning and disinfection methodologies fail to remove persistent bacterial biofilms within the intricate anatomical structures. Recently, the field of nanotechnology has emerged as a promising frontier with numerous biomedical applications. Among the most notable contributions of nanotechnology are nanoparticles, which possess antimicrobial, antifungal, and antiviral properties. Nanoparticles cause the destructuring of bacterial walls, increasing the permeability of the cell membrane, stimulating the generation of reactive oxygen species, and interrupting the replication of deoxyribonucleic acid through the controlled release of ions. Thus, they could revolutionize endodontics, obtaining superior results and guaranteeing a promising short- and long-term prognosis. Therefore, chitosan, silver, graphene, poly(lactic) co-glycolic acid, bioactive glass, mesoporous calcium silicate, hydroxyapatite, zirconia, glucose oxidase magnetic, copper, and zinc oxide nanoparticles in endodontic therapy have been investigated in the present review. The diversified antimicrobial mechanisms of action, the numerous applications, and the high degree of clinical safety could encourage the scientific community to adopt nanoparticles as potential drugs for the treatment of endodontic diseases, overcoming the limitations related to antibiotic resistance and eradication of the biofilm.

Daily use of mouthwash is generally recommended to control dental plaque development and limit further adhesion of oral bacteria. To this purpose, Chlorhexidine di-gluconate (CHG)-containing products are still the most used antiseptic in oral health. The aim of this study was to compare the antimicrobial and antibiofilm activity of three different mouthwash commercial formulations containing CHG at the same concentration (0.2%) on the main etiological agent of dental plaque, Streptococcus mutans (S. mutans). Liquid Chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used to confirm the CHG concentration in the commercial formulations. The Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal concentration (MBC) were measured to evaluate the antimicrobial activity of mouthwashes on planktonic cells. The biofilm prevention concentration (BPC) and CHG formulation activity towards mature biofilm were investigated. Both total cell titer and viability in S. mutans pregrown biofilms were evaluated after treatment with formulations at different time points and concentrations, using Crystal Violet (CV) and tetrazolium dye assay (MTT). The Shapiro–Wilk and Levene tests were used to evaluate the normality and overall homogeneity of the datasets, respectively. The chi-square test, Fischer’s exact test and Student’s t-test were used to evaluate the inhibitory capacity of the commercial formulations in CV and MTT assays. Results showed that even though only slight differences in MIC and MBC values were found on planktonic bacteria, the antibiofilm effect of the different formulations exhibited wide variation when mature biofilms were treated. In addition, results were discussed based on the different compositions of the three formulations, suggesting that herbal extracts, when present in mouthwash formulations, may not always have a beneficial effect, especially when mature biofilms are concerned.

Considering the increasing need for oral and dental care in the elderly, teledentistry has been proposed to improve the education of elderly patients in oral health maintenance and risk factor control, identify patients’ concerns in advance, facilitate monitoring, and save time and money. The present cross-sectional analysis of Google search data through real-time surveillance with Google Trends aimed to determine Google users’ interest in oral and dental needs and teledentistry applications in the elderly, and to compare search volumes before and after the COVID-19 outbreak. Extracted CVS data were qualitatively analyzed. Pearson and Spearman correlation analyses were performed between searches for “elderly” and “teledentistry”, and all the oral and dental needs and teledentistry applications. The Mann–Whitney U test compared search volumes in the 36 months before and after the beginning of the COVID-19 pandemic. Google users’ interest in the elderly and related oral and dental needs was diffusely medium–high, while teledentistry and its applications were of lower interest. Interest in teledentistry and its applications was strongly related to interest in the older population, which is consistent with the assumption that older adults represent the population segment that could benefit most from these tools. A positive correlation was also found between searches for “Elderly” and searches for almost all oral and dental needs typical of the geriatric population. Search volumes increased significantly after the outbreak of the COVID-19 pandemic. More information about teledentistry should be disseminated to increase knowledge and awareness, especially among older patients, about its indications, applications, and advantages.

The present umbrella review aimed to characterize the type and regimen of antibiotics administered locally and/or systemically, alone or in combination with surgical and nonsurgical treatments, for peri-implantitis and to evaluate and compare the associated clinical, radiographic, and crevicular peri-implant outcomes. The secondary objective was to determine the most effective antibiotic type, route of administration, regimen, and protocols (antibiotics alone or in combination with other approaches) for treating peri-implantitis. The study protocol, which was developed in advance under the PRISMA statement, was registered at PROSPERO (CRD42022373957). BioMed Central, Scopus, MEDLINE/PubMed, the Cochrane Library databases, and the PROSPERO registry were searched for systematic reviews through 15 November 2022. Of the 708 records found, seven reviews were included; three were judged of a critically low and four of low quality through the AMSTAR 2 tool. Locally administered antibiotics alone or as an adjunct to surgical or nonsurgical treatments for peri-implantitis showed favorable outcomes, albeit with limited evidence. The administration of systemically-delivered antibiotics in combination with nonsurgical or surgical treatments remained questionable. Local plus systemic antibiotics have not been shown to have durable efficacy. Due to the heterogeneity of reported antibiotic types, routes, regimens, and protocols, no definitive conclusions could be drawn regarding the most effective antibiotic use in treating peri-implantitis.

Recent developments in the monetary situation in West Africa, in particular the transformation for the CFA franc area and the project to build a single currency for the CEDEAO/ECOWAS, require a systematic review of the assumptions underlying the formation of monetary unions. The article provides a critical review of the traditional theoretical foundations of optimal currency areas (OCAs) and their subsequent amendments, in light of the problems that emerged in the most relevant monetary unions. On specific points, a comparison is made between the eurozone and the CFA zone. The article then investigates the specific characteristics of the monetary area affected by the reform project, and finally it indicates the main lines along which the project of a common currency to all the states that currently make up the CEDEAO/ECOWAS could evolve, identifying four possible alternative roadmaps. JEL codes: F33, F53, F45

Le evoluzioni recenti della situazione monetaria in Africa dell’Ovest, in particolare la trasformazione per l’area del franco CFA e il progetto di costruzione di una moneta unica per la CEDEAO/ECOWAS, impongono una revisione sistematica delle ipotesi che sottostanno alla costituzione di unioni monetarie. L’articolo fornisce una rassegna critica dei fondamenti teorici tradizionali delle aree monetarie ottimali (AMO) e dei loro successivi emendamenti, alla luce dei problemi emersi nelle principali unioni monetarie. Su specifici punti viene effettuata una comparazione fra eurozona e zona CFA. Successivamente l’articolo indaga le caratteristiche specifiche dell’area monetaria interessata dal progetto di riforma, e infine indica le principali linee lungo le quali potrebbe evolvere il progetto di una moneta comune all’insieme degli stati che compongono attualmente la CEDEAO/ECOWAS, individuando quattro possibili percorsi alternativi. Recent developments in the monetary situation in West Africa, in particular the transformation for the CFA franc area and the project to build a single currency for the CEDEAO/ECOWAS, require a systematic review of the assumptions underlying the formation of monetary unions. The article provides a critical review of the traditional theoretical foundations of optimal currency areas (OCA) and their subsequent amendments, in light of the problems that emerged in the most relevant monetary unions. On specific points, a comparison is made between the eurozone and the CFA zone. The article then investigates the specific characteristics of the monetary area affected by the reform project, and finally indicates the main lines along which the project of a common currency to all the states that currently make up the CEDEAO/ECOWAS could evolve, identifying four possible alternative roadmaps. JEL codes:F33, F53, F45

La recente crisi dell’eurozona, insieme all’annunciata riforma del franco della Comunità Finanziaria Africana e ai progetti di costituzione di nuove aree valutarie in diversi continenti, ha riportato il tema delle unioni monetarie in primo piano nel dibattito economico. La presente introduzione intende mostrare come i contributi contenuti in questo numero speciale arricchiscano tale dibattito. The recent eurozone crisis, together with the announced reform of the African Financial Community franc and plans to establish new currency areas in different continents, brought the issue of monetary unions back to the fore in the economic debate. The present introduction aims at showing how the contributions contained in this special issue can consistently enrich this debate. JEL codes: E42, F33, F45

In Winter 2020, Italy, and in particular the Lombardy region, was the first country in the Western hemisphere to be hit by the COVID-19 pandemic. Plasma from individuals recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first therapeutic tool adopted to counteract the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In this retrospective cohort study, we report the experience of the city hospital of Mantua, Lombardy region, on the compassionate use of CCP in patients hospitalized for severe COVID-19. Between April 2020 and April 2021, 405 consecutive COVID-19 patients received 657 CCP units with a median anti-SARS-CoV-2 neutralizing antibody (nAb) titer of 160 (interquartile range (IQR), 80–320). Their median age was 68 years (IQR, 56–78 years), and 62% were males. At enrollment, 55% of patients had an increased body mass index (BMI), and 25.6% had at least three comorbidities. The 28-day crude mortality rate was 12.6% (51/405). Young age (

Abrikossoff’s tumour is a rare benign soft tissue neoplasm that can occur in any part of the body, including the orofacial region. The tumour is usually benign, but there are reports of cases in which the tumour shows a locally aggressive behaviour, malignancy, and distant metastases. The aetiology is unknown, since several studies have shown that different cells are involved. In the present case, a 36-year-old Dominican woman was referred to the Department of Oral and Maxillofacial Surgery in Policlinico Federico II, Naples with a circumscribed lesion and sessile nodule on the dorsum of the tongue measuring about 17 mm in diameter. The treatment consisted of an excisional biopsy performed on the basis of the diagnostic hypothesis of Abrikossoff’s tumour, which was confirmed by histopathological analysis and histochemistry and immunohistochemistry evaluation. Abrikossoff’s tumour is an uncommon neoplasm which must be carefully diagnosed considering all the histological and clinical aspects in order to be treated correctly.