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(1) Background: Head and neck cancer (HNC) is a major public health challenge worldwide, with oral squamous cell carcinoma (OSCC) being the predominant form. Despite advances in treatment, OSCC remains a major cause of morbidity and mortality due to delayed diagnosis and limited therapeutic efficacy. This study reviews omics technologies to assess new salivary biomarkers for the early detection of OSCC. (2) Methods: A comprehensive literature search in the last 20 years identified four relevant studies focusing on salivary biomarkers in OSCC. (3) Results: Proteomic and genomic analyses revealed significant changes in salivary composition between OSCC patients and healthy controls, suggesting promising diagnostic and prognostic biomarkers. However, studies showed varying degrees of bias, indicating the need for further research and improved standardization. (4) Conclusions: Saliva, with its advantages of ease of collection, minimal invasiveness, and potential for large-scale screening, is an emerging promising substrate for non-invasive biomarker research. Nonetheless, there is a need for improved biomarker sensitivity and specificity; currently, histological examination remains the golden standard.

Background: Sleeve lobectomy with bronchoplasty is a safe surgical technique for the management of lung cancer and endobronchial localization of extrapulmonary cancers. However, anastomotic complications can occur, and treatment strategies are not standardized. Methods: Data from 280 patients subjected to bronchoplasty were retrospectively analyzed, focusing on surgical techniques, anastomotic complications, and their management. Multivariate analysis was performed, and Kaplan–Meier curves were used to determine survival. Results: Ninety percent of 280 surgeries were for lung cancer. Anastomotic complications occurred in 6.42% of patients: late stenosis in 3.92% and broncho-pleural fistula in 1.78%. The median survival was 65.90 months (95% CI = 41.76–90.97), with no difference (p = 0.375) for patients with (51.28 months) or without (71.03 months) anastomotic complications. Mortality at 30 days was higher with anastomotic complications (16.7% vs. 3%, p = 0.014). Multivariable analysis confirmed pathological stage (N+) as a risk factor for anastomotic complications (p = 0.016). Our mortality (3.93%) and morbidity rate (41.78%) corresponded to recent series results. Conclusions: In our experience, surgery is preferred to avoid life-threatening complications in bronchopleural fistulas. Bronchoscopic balloon dilatation is preferred for benign strictures. The nodal stage is related to complications (p = 0.0014), reflecting the aggressiveness of surgery, which requires extended radical lymphadenectomy.

Solenopsis invicta, a South American ant species from the Formicidae family (subfamily Myrmicinae), has recently established a stable settlement in Europe, raising public health concerns due to its venomous stings. The venom of S. invicta is rich in bioactive molecules, particularly piperidine alkaloids such as solenopsin A and peptides (Sol 1–4). These compounds have been implicated in various health applications, including antimicrobial, anti-inflammatory, and antitumour activities. While previous reviews have focused on the ecological and allergenic risks posed by S. invicta, this scoping review aims to evaluate the potential therapeutic uses of S. invicta venom by summarizing existing scientific evidence and providing a novel synthesis of recent research on its bioactive components. Furthermore, this study, by describing the unique biological aspects of S. invicta, provides an overview of its direct impact on public health, highlighting new findings on the venom’s role in inhibiting bacterial biofilm formation and modulating cancer growth pathways through gene regulation. A search of databases (PubMed, Scopus, Science Direct, and Cochrane Library) identified 12,340 articles, from which 11 studies met the eligibility criteria. These studies included seven microbiological investigations and four studies on tumour cell lines and animal models. The findings suggest that S. invicta venom could inhibit biofilm formation, combat fungal infections, and suppress tumour growth. However, further research, including clinical trials, is required to fully elucidate the safety and efficacy of these bioactive molecules in human medicine, for their potential use in drug discovery to counteract several diseases, including cancer.

Background and Objectives: The purpose of this case report is to examine the management of vestibular bone fenestration during alveolar socket preservation using the Periosteal Inhibition (PI) approach. Here, for the first time, the PI technique, which has been shown to be successful in maintaining intact cortical bone, is examined in the context of a bone defect. Materials and Methods: After an atraumatic extraction of a damaged tooth, a vestibular bone fenestration was discovered in the 62-year-old male patient. To shield the defect, a non-resorbable PTFE membrane (OSSEO GUARD by Zimmer Biomet) was positioned between the mucosa and the fenestration site. A resorbable porcine gelatin sponge (SPONGOSTANTM) was used to achieve hemostasis, and a 5/0 PGCL absorbable suture was used to close the wound. A CBCT scan was performed, and a dental implant was inserted after 4 months. Results: After 4 months, the case demonstrated positive results, with full cortical remodeling and preservation of the original bone proportions. The fenestration completely healed, proving that the PI approach works even in the presence of bone flaws in cortical bone that is still intact. Conclusions: This is the first case report that shows that vestibular bone fenestration can be successfully treated with the PI approach. It has now been demonstrated that the procedure, which hitherto needed an undamaged cortical bone to work, can help bone abnormalities to repair completely. These results imply that the PI technique is a flexible and useful approach that provides predictable results in dental surgery for treating different types of alveolar bone abnormalities. Its use might be expanded with more study to include bone dehiscence treatment.

Background: The surgical removal of impacted mandibular third molars is routine in oral and maxillofacial surgery and common postoperative complications are widely reported in the literature. Therefore, this prospective split-mouth study aims to compare the postoperative sequelae of piezoelectric surgery versus conventional surgery of the lower third molar, focusing on pain and swelling. Methodology: In total, 41 patients were treated under local anesthesia and surgical removal on one side of their mouth was performed using conventional rotary surgery (micromotor) while the other side’s was by piezosurgery, with an interval of 15 days from the previous procedure (82 extraction sites); in addition, pain and swelling analyses were conducted. Results: The pain analysis demonstrated a median of one day of pain in patients treated with piezoelectric surgery compared to two days with conventional surgery (p < 0.001). The probability of not feeling pain was greater in sites treated with experimental surgery on the first and second days (p < 0.001). The swelling was worse in places treated with the conventional method, with the most significant difference being the distance between the angle of the mandible and the upper lip vermilion on both days and the more subtle difference between the angle of the mandible and the anterior nasal spine on the seventh day. Conclusions: When a piezosurgical unit is used, according to the literature, is well known that it takes more time to perform the surgical extraction of third molars. Despite that, our results show that it causes less pain postoperatively, with faster improvement and a quicker reduction in swelling compared to conventional surgery.

Pulmonary cancer is often associated with systemic inflammation and poor nutritional status and these two aspects are strongly correlated and related to the scarce infiltration of a tumor by immune cells. We reviewed all English literature reviews from 2000 to 2024 from PubMed, Scopus and Google Scholar, including original articles, review articles, and metanalyses. We excluded non-English language articles and case reports/case series. Generally speaking, nutritional and inflammatory status largely affect medium and long-term prognosis in lung cancer patients. A correct stratification of patients could improve their preoperative general functional nutritional and inflammatory status, minimizing, therefore, possible treatment complications and improving long-term prognosis.

Artificial Intelligence (AI) and Machine Learning (ML) approaches that could learn from large data sources have been identified as useful tools to support clinicians in their decisional process; AI and ML implementations have had a rapid acceleration during the recent COVID-19 pandemic. However, many ML classifiers are “black box” to the final user, since their underlying reasoning process is often obscure. Additionally, the performance of such models suffers from poor generalization ability in the presence of dataset shifts. Here, we present a comparison between an explainable-by-design (“white box”) model (Bayesian Network (BN)) versus a black box model (Random Forest), both studied with the aim of supporting clinicians of Policlinico San Matteo University Hospital in Pavia (Italy) during the triage of COVID-19 patients. Our aim is to evaluate whether the BN predictive performances are comparable with those of a widely used but less explainable ML model such as Random Forest and to test the generalization ability of the ML models across different waves of the pandemic.

Risk stratification for malignant ventricular arrhythmias and sudden cardiac death is a daunting task for physicians in daily practice. Multiparametric mapping sequences obtained via cardiovascular magnetic resonance imaging can improve the risk stratification for malignant ventricular arrhythmias by unveiling the presence of pathophysiological pro-arrhythmogenic processes. However, their employment in clinical practice is still restricted. The present review explores the current evidence supporting the association between mapping abnormalities and the risk of ventricular arrhythmias in several cardiovascular diseases. The key message is that further clinical studies are needed to test the additional value of mapping techniques beyond conventional cardiovascular magnetic resonance imaging for selecting patients eligible for an implantable cardioverter defibrillator.

In tissue formation and regeneration processes, cells often move collectively, maintaining connections through intercellular adhesions. However, the specific roles of cell–substrate and cell-to-cell mechanical interactions in the regulation of collective cell migration are not yet fully understood. Finite element modeling (FEM) may be a way to assess more deeply the biological, mechanical, and chemical phenomena behind cell adhesion. FEM is a powerful tool widely used to simulate phenomena described by systems of partial differential equations. For example, FEM provides information on the stress/strain state of a cell adhering to a substrate, as well as on its mechanobiological behavior. This review paper, after briefly describing basic principles of cell adhesion, surveys the most important studies that have utilized FEM to investigate the structural response of a cell adhering to a substrate and how the forces acting on the cell–substrate adhesive structures affect the global cell mechanical behavior.

(1) Background: The aim of this study was to compare the histopathological features of syndromic and non-syndromic odontogenic keratocysts (OKs) using conventional and Confocal Laser Scanning Microscopy (CLSM) with their biological behaviour. (2) Methods: Data from the medical records of 113 patients with histological diagnosis of (single and/or multiple) OKs were collected. Globally, 213 OKs (120 syndromic and 93 sporadic) were retrieved, and their histological slides were re-evaluated with conventional H&E staining and with autofluorescence on the same slides using CLSM (Nikon Eclipse E600 microscope). (3) Results: Syndromic OKs showed more satellite cysts than sporadic cases, as well as a basophilic layer in the basement membrane, which was absent in sporadic OKs; both were highlighted with CLSM. The basement membrane in syndromic OKs appeared amorphous and fragile, thus possibly being responsible for the epithelial detachment and collapse, with scalloped features. Furthermore, the basal epithelial layers in such cases also showed increased cellularity and proliferative activity. All these histological features may possibly justify their higher tendency to recur. (4) Conclusions: CLSM is useful advanced technology that could help to quickly and easily discriminate between syndromic and non-syndromic OKs and to more accurately predict their biological behaviour in order to set fitter clinico-radiological follow-ups for individual patients.

Thermoplastic polyurethane (TPU) is a polymer used in a variety of fields, including medical applications. Here, we aimed to verify if the brush and bar coater deposition techniques did not alter TPU properties. The topography of the TPU-modified surfaces was studied via AFM demonstrating no significant differences between brush and bar coater-modified surfaces, compared to the un-modified TPU (TPU Film). The effect of the surfaces on planktonic bacteria, evaluated by MTT assay, demonstrated their anti-adhesive effect on E. coli, while the bar coater significantly reduced staphylococcal planktonic adhesion and both bacterial biofilms compared to other samples. Interestingly, Pearson’s R coefficient analysis showed that Ra roughness and Haralick’s correlation feature were trend predictors for planktonic bacterial cells adhesion. The surface adhesion property was evaluated against NIH-3T3 murine fibroblasts by MTT and against human fibrinogen and human platelet-rich plasma by ELISA and LDH assay, respectively. An indirect cytotoxicity experiment against NIH-3T3 confirmed the biocompatibility of the TPUs. Overall, the results indicated that the deposition techniques did not alter the antibacterial and anti-adhesive surface properties of modified TPU compared to un-modified TPU, nor its bio- and hemocompatibility, confirming the suitability of TPU brush and bar coater films in the biomedical and pharmaceutical fields.

(1) Background: Gingival cancer has a significant incidence and is often diagnosed at advanced stages. The aim of this paper is to highlight its clinical aspects on the basis of a case series analysis in order to promote awareness and improve the diagnosis process. (2) Methods: Oral cancers diagnosed and treated at three Italian University Hospitals over ten years were retrospectively investigated. Cancer location on the gingiva, edentulous ridge, and retromolar pad was addressed. Data regarding clinical features, stage at the diagnosis, and time from presenting symptoms to first medical consultation were retrieved. (3) Results: Thirty-three cancers located on the gingiva, edentulous ridge, and retromolar pad were retrieved from 276 total oral cancer cases (11.9%). A median of 50 days (range 2–300) passed for the patient to seek for a medical evaluation. At the time of diagnosis, 63.3% were advanced stage cancers, mainly located at the mandible (91%), especially in the retromolar pad (48.5%) and the edentulous alveolar ridge (24.2%). Lesions were red (45.5%), red and white (45.4%), or white (9.1%), appearing as an ulcer (69.7%), exophytic mass (12.1%) or flat lesion (12.1%). Sixty-six percent of cancers were completely asymptomatic, regardless their clinical appearance. A statistically significant association between the time from the presentation of symptoms to the first medical consultation and the cancers stage was found. (4) Conclusions: The clinical appearance of gingival cancer is very polymorphous; its understanding may be significant to improve patient education and early medical consultation.

This case report presents an orthodontic treatment conducted on a 13-year-old girl with bilateral Class II malocclusion and a mandibular impacted canine. The presence of an impacted tooth necessitates careful consideration of the timing of orthodontic treatment, the appropriate surgical procedure to expose the tooth, the specific orthodontic mechanics involved, and the potential problems that may arise, all of which depend on the type and location of the canine impaction in the jaw. The treatment plan included a surgical procedure to expose the impacted tooth and orthodontic traction to guide it into position. Correction of the Class II Division 1 malocclusion utilized a specialized technique called the “reverse pin”, reducing vertical side effects. The revised version maintains clarity and key information about the case report and treatment.

Background and Objectives: The aim of this study was to evaluate the correlation between the mandibular arch shape and the vertical skeletal pattern in growing patients. Materials and Methods: A total of 73 Caucasian patients (33 males and 40 females; mean age 9.4) were retrospectively enrolled from a pool of patients treated in chronological order at the Department of Orthodontics, University of Foggia, Italy, from April 2018 to December 2021. Each patient received a laterolateral radiograph and a digital scan of the dental arch. Eight cephalometric parameters (lower gonial angle, intermaxillary angle, divergence angle, Wits index, Jarabak ratio, OP-MP angle, PP-OP angle, and ANB) and five dental measurements (posterior mandibular arch width, anterior mandibular arch width, mandibular occlusal angle, posterior width on distobuccal molar cusps, and molar angle) were analyzed and then compared. A Spearman’s rho correlation test between the cephalometric measurements and the dental measurements was performed. Statistical significance was set at p < 0.05. Results: A negative statistically significant correlation was found between the Jarabak ratio and the intermolar angle; a statistically significant correlation was also observed between the Wits index, the posterior mandibular width, and the occlusal mandibular angle; the ANB angle and the occlusal mandibular angle; the intermaxillary angle (PP-PM) and the mandibular occlusal angle, posterior mandibular width on the disto-vestibular cusp, and the intermolar angle; and the OP-MP angle and mandibular occlusal angle and the posterior mandibular width on the disto-vestibular cusp. Conclusions: The mandibular arch form may be related to certain predisposing features in craniofacial morphology, such as jaw divergence, the Jarabak ratio, and the intermaxillary angle.

Levels of bone turnover markers (BTM) can be measured using saliva. The aim of the present study was to determine the Biological Variability of BTM in young subjects, on serial biological salivary samples. Saliva samples of 20 apparently healthy young subjects (9 females and 11 males) have been analyzed. Samples collected using salivette with cotton swabs were obtained three times every 15 days. PTHrP; TRAcP-5b and P1NP have been assayed. The ANOVA test was used to calculate intra and interindividual variance (CVI and CVG). The individuality index (II) and reference change value (RCV) were evaluated for the clinically significant variation between two results in the same individual. CVI was highest for PTHrP and lowest for P1NP while CVG was highest for TRAcP-5b. RCV was maximum for PTHrP and minimum for P1NP. The critical difference (RCV) is of particular interest in evaluating variations in the concentrations of BMT on the salivary matrix during oral pathologies and/or dental treatments The salivary dosage of BMT during dental treatments could be fundamental to establishing establish the timing of the treatment and, in the case of orthodontic treatments, to evaluate the effectiveness of the applied forces.

The marine sponge Lendenfeldia sp., collected from the Southern waters of Taiwan, was subjected to chemical composition screening, resulting in the isolation of four new 24-homoscalarane compounds, namely lendenfeldaranes R–U (1–4). The structures and relative stereochemistry of the new metabolites 1–4 were assigned based on NMR studies. The absolute configurations of compounds 1–4 were determined by comparing the calculated and experimental values of specific optical rotation. The antioxidant and anti-inflammatory activities of the isolated compounds were assayed using superoxide anion generation and elastase release assays. These assays are used to determine neutrophilic inflammatory responses of respiratory burst and degranulation. Compounds 2 and 4 inhibited superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB) with IC50: 3.98–4.46 μM. Compounds 2 and 4 inhibited fMLP/CB-induced elastase release, with IC50 values ranging from 4.73 to 5.24 μM. These findings suggested that these new 24-homoscalarane compounds possess unique structures and potential anti-inflammatory activity.

Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have been identified as pivotal players in the onset and advancement of HNSCCs, operating as either oncogenes or tumor suppressors. Distinctive miR patterns identified in tumor samples, as well as in serum, plasma, or saliva, from patients have significant clinical potential for use in the diagnosis and prognosis of HNSCCs and as potential therapeutic targets. The aim of this study was to identify previous systematic reviews with meta-analysis data and clinical trials that showed the most promising miRs in HNSCCs, enclosing them into a biomolecular signature to test the prognostic value on a cohort of HNSCC patients according to The Cancer Genome Atlas (TCGA). Three electronic databases (PubMed, Scopus, and Science Direct) and one registry (the Cochrane Library) were investigated, and a combination of keywords such as “signature microRNA OR miR” AND “HNSCC OR LSCC OR OSCC OR oral cancer” were searched. In total, 15 systematic literature reviews and 76 prognostic clinical reports were identified for the study design and inclusion process. All survival index data were extracted, and the three miRs (miR-21, miR-155, and miR-375) most investigated and presenting the largest number of patients included in the studies were selected in a molecular biosignature. The difference between high and low tissue expression levels of miR-21, miR-155, and miR-375 for OS had an HR = 1.28, with 95% CI: [0.95, 1.72]. In conclusion, the current evidence suggests that miRNAs have potential prognostic value to serve as screening tools for clinical practice in HNSCC follow-up and treatment. Further large-scale cohort studies focusing on these miRNAs are recommended to verify the clinical utility of these markers individually and/or in combination.

COVID-19 (Coronavirus Disease 2019) is an emerging viral disease caused by the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which leads to severe respiratory infections in humans. The first reports came in December 2019 from the city of Wuhan in the province of Hubei in China. It was immediately clear that children developed a milder disease than adults. The reasons for the milder course of the disease were attributed to several factors: innate immunity, difference in ACE2 (angiotensin-converting enzyme II) receptor expression, and previous infections with other common coronaviruses (CovH). This literature review aims to summarize aspects of innate immunity by focusing on the role of ACE2 expression and viral infections in children in modulating the antibody response to SARS-CoV-2 infection. This review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles deemed potentially eligible were considered, including those dealing with COVID-19 in children and providing more up-to-date and significant data in terms of epidemiology, prognosis, course, and symptoms, focusing on the etiopathogenesis of SARS-CoV-2 disease in children. The bibliographic search was conducted using the search engines PubMed and Scopus. The following search terms were entered in PubMed and Scopus: COVID-19 AND ACE2 AND Children; COVID-19 AND Immunity innate AND children. The search identified 857 records, and 18 studies were applicable based on inclusion and exclusion criteria that addressed the issues of COVID-19 concerning the role of ACE2 expression in children. The scientific literature agrees that children develop milder COVID-19 disease than adults. Milder symptomatology could be attributed to innate immunity or previous CovH virus infections, while it is not yet fully understood how the differential expression of ACE2 in children could contribute to milder disease.

Inflammation is a critical defense mechanism that is utilized by the body to protect itself against pathogens and other noxious invaders. However, if the inflammatory response becomes exaggerated or uncontrollable, its original protective role is not only demolished but it also becomes detrimental to the affected tissues or even to the entire body. Thus, regulating the inflammatory process is crucial to ensure that it is resolved promptly to prevent any subsequent damage. The role of neutrophils in inflammation has been highlighted in recent decades by a plethora of studies focusing on neutrophilic inflammatory diseases as well as the mechanisms to regulate the activity of neutrophils during the overwhelmed inflammatory process. As natural products have demonstrated promising effects in a wide range of pharmacological activities, they have been investigated for the discovery of new anti-inflammatory therapeutics to overcome the drawbacks of current synthetic agents. Octocorals have attracted scientists as a plentiful source of novel and intriguing marine scaffolds that exhibit many pharmacological activities, including anti-inflammatory effects. In this review, we aim to provide a summary of the neutrophilic anti-inflammatory properties of these marine organisms that were demonstrated in 46 studies from 1995 to the present (April 2023). We hope the present work offers a comprehensive overview of the anti-inflammatory potential of octocorals and encourages researchers to identify promising leads among numerous compounds isolated from octocorals over the past few decades to be further developed into anti-inflammatory therapeutic agents.

The COVID-19 pandemic, starting in 2020, has presented a major challenge in terms of early diagnosis and the subsequent containment and management of severe cases. The spread of viruses such as monkeypox in non-endemic countries is now creating new difficulties for healthcare professionals. Proper case definition and clinical examination are crucial for the early identification of suspected cases. For this reason, we performed a review of the literature in order to report the first signs, which are useful for healthcare providers for early case identification. Since 2022 to date, 86,930 laboratory-confirmed cases and 1051 probable cases have been reported worldwide, and of these, 116 were fatal cases and, for the first time, most of the cases were registered in countries that have not historically reported monkeypox and that lack direct or immediate epidemiological links to areas of West or Central Africa where the disease is endemic. Patients with Monkeypox experience prodromal symptoms, such as fever, fatigue, headache, muscle aches, and a rash after an incubation period of 5–21 days. The disease is usually self-limiting within 2–4 weeks but can lead to complications, such as pneumonia, encephalitis, kidney injury, and myocarditis in children, pregnant individuals, and those with weakened immune systems. The case–fatality ratio is between 1 and 10%. Today, prevention campaigns and the control of human monkeypox are the best weapons to prevent infection and stop transmission. Prevention strategies, such as avoiding contact with sick or dead animals, and the proper preparation of all foods containing animal meat or parts, should be adopted. Furthermore, close contact with infected people or contaminated materials should be avoided to prevent human-to-human transmission.

Virtual surgical planning for CAD/CAM mandibular reconstruction by titanium prosthesis was recently reported for resected cases. Even if some advantages are evident, difficulties that may arise for TMJ function after reconstruction originate from prosthesis contamination through oral mucosa dehiscence. In these two cases reported of mandibular reconstruction after resection of ameloblastoma by custom-made CAD/CAM titanium prosthesis, the procedures were aimed to preserve the TMJ glenoid cavity and articular disc avoiding functional problems for hemi-mandibular resections that included the condyle (as in case #1) or with condylar preservation (as in case #2) and avoiding intraoral incisions in both cases. The entire surgical planning and prosthetic fabrication were explained with specifications and the sequence of the surgical procedure. Finite elements analysis (FEA) was performed to check the force distribution and efficacy of the prosthetic device (case 1 with hemi-mandibular resection and rehabilitation). Although successful in these two cases, surgical reconstruction of the mandibular defect after resection by a CAD-CAM custom-made prosthesis still shows some drawbacks and failure risks. Several advantages of this technique and the surgical success in these two cases were presented, but limitations and side effects must be considered when cases are selected.

Background. A large increase in multi-drug-resistant Acinetobacter baumannii, especially carbapenem-resistant strains, occurred during the first two years of the COVID-19 pandemic, posing important challenges in its treatment. Cefiderocol appeared to be a good option for the treatment of Carbapenem-resistant Acinetobacter baumannii (CR-Ab), but to date, the guidelines and evidence available are conflicting. Methods. We retrospectively included a group of patients with CR-Ab infections (treated with colistin- or cefiderocol-based regimens) at Padua University Hospital (August 2020–July 2022) and assessed predictors of 30-day mortality, and differences in microbiological and clinical treatment. To evaluate the difference in outcomes, accounting for the imbalance in antibiotic treatment allocation, a propensity score weighting (PSW) approach was adopted. Results. We included 111 patients, 68% males, with a median age of 69 years (IQR: 59–78). The median duration of antibiotic treatment was 13 days (IQR:11–16). In total, 60 (54.1%) and 51 (45.9%) patients received cefiderocol- and colistin-based therapy, respectively. Notably, 53 (47.7%) patients had bloodstream infections, while 58 (52.3%) had pneumonia. Colistin was combined in 96.1%, 80.4%, and 5.8% of cases with tigecycline, meropenem, and fosfomycin, respectively. Cefiderocol was combined in 13.3%, 30%, and 18.3% of cases with fosfomycin, tigecycline, and meropenem, respectively. At the baseline, the two treatment groups significantly differed in age (patients treated with colistin were significantly older), the prevalence of diabetes and obesity (more frequent in the group treated with colistin), length of stay (longer in the group receiving cefiderocol), and type of infection (BSI were more frequent in the group receiving cefiderocol). The proportion of patients who developed acute kidney injury was significantly higher in the colistin group. By using PSW, no statistically significant differences emerged for mortality or clinical and microbiological cure between the two groups. No independent predictors were detected for hospital mortality or clinical cure, while for the length of stay, the only selected predictor was age, with a non-linear effect (p-value 0.025 for non-linearity) on the prolongation of hospital stay of 0.25 days (95% CI 0.10–0.39) at increasing ages (calculated over the IQR). Conclusions. Cefiderocol treatment did not differ in terms of main outcomes and safety profile from colistin-based regimens. More prospective studies with a larger number of patients are required to confirm our results.

The aim of this study was to investigate methylone and its metabolites concentration in oral fluid following controlled increasing doses, focusing on the effect of oral fluid pH. Samples were obtained from a clinical trial where twelve healthy volunteers participated after ingestion of 50, 100, 150 and 200 mg of methylone. Concentration of methylone and its metabolites 4-hydroxy-3-methoxy-N-methylcathinone (HMMC) and 3,4-methylenedioxycathinone in oral fluid were measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Pharmacokinetic parameters were estimated, and the oral fluid-to-plasma ratio (OF/P) at each time interval was calculated and correlated with the oral fluid pH using data from our previous study in plasma. Methylone was detected at all time intervals after each dose; MDC and HMMC were not detectable after the lowest dose. Oral fluid concentrations of methylone ranged between 88.3–503.8, 85.5–5002.3, 182.8–13,201.8 and 214.6–22,684.6 ng/mL following 50, 100, 150 and 200 mg doses, respectively, peaked between 1.5 and 2.0 h, and were followed by a progressive decrease. Oral fluid pH was demonstrated to be affected by methylone administration. Oral fluid is a valid alternative to plasma for methylone determination for clinical and toxicological studies, allowing for a simple, easy and non-invasive sample collection.

Aim: The authors provided an accurate, simple, and noninvasive method for matching the intraoral scan with facial scan of a patient, without the need of a cone beam computed tomography (CBCT). Materials and methods: Three different facial scans were acquired: the first one with the mouth closed, the second one with a voluntary “social smile”, and the last one scanned the face with a lip-and-cheek retractor with dental arches in occlusion. The base of this method is to superimpose the area of the dental arches acquired by a face scanner with the same area derived by an intraoral scanner. Result: An accurate matching of intraoral and facial scans can be achieved without the risks of radiation exposure. Conclusions: The virtual patient helps the orthodontist to improve both diagnosis and treatment planning: a three-dimensional digital smile design can be performed, the patient’s smile can then be analyzed in the context of the lips, and the teeth can be moved to achieve a consonant and balanced smile. All this information can be integrated in a clear aligner therapy or an indirect bonding procedure, enhancing outcomes in the facial esthetics.

The progressive aging of the population and the consequent growth of individuals with neurological diseases and related chronic disabilities, will lead to a general increase in the costs and resources needed to ensure treatment and care services. In this scenario, telemedicine and e-health solutions, including remote monitoring and rehabilitation, are attracting increasing interest as tools to ensure the sustainability of the healthcare system or, at least, to support the burden for health care facilities. Technological advances in recent decades have fostered the development of dedicated and innovative Information and Communication Technology (ICT) based solutions, with the aim of complementing traditional care and treatment services through telemedicine applications that support new patient and disease management strategies. This is the background for the REHOME project, whose technological solution, presented in this paper, integrates innovative methodologies and devices for remote monitoring and rehabilitation of cognitive, motor, and sleep disorders associated with neurological diseases. One of the primary goals of the project is to meet the needs of patients and clinicians, by ensuring continuity of treatment from healthcare facilities to the patient’s home. To this end, it is important to ensure the usability of the solution by elderly and pathological individuals. Preliminary results of usability and user experience questionnaires on 70 subjects recruited in three experimental trials are presented here.

The Punica granatum L. is an ancient fruit plant native to south-western Asia. It belongs to the Litraceae family and of its genus we have only one other Punica protopunic species. The fruit is rich in polyphenols, whose extract is consumed as a food and is considered safe. In medicine, it is used for its antioxidant properties; it has a rich component of tannic polyphenols among which the most bioactive are: punicalagin (flavonoids) and anthocyanins (delphinidin, cyanidin, pelargonidin), which are found mainly in the skins and in the pericarp; however, all the parts of the Punica granatum are used for therapeutic purposes as anti-inflammatories and analgesics and in diabetes and cardio-vascular disease. Punica granatum extracts also show interesting anticancer activities in influencing tumorgenesis and angiogenesis and cell transformation and proliferation. The purpose of this scoping review is to summarize all the scientific evidence on the possible applications of Punica granatum extracts in the treatment and prevention of oral cavity tumors to investigate the anticancer properties of the active ingredients extracted from Punica granatum. Methods: The scoping review was carried out following the PRISMA-ScR checklist; the search was performed on three databases (Scopus, Science direct and PubMed) and one registry (Cochrane library). Results: The search produced a number of bibliographic sources equal to 11,403; with the removal of duplicates, 670 potentially admissible articles were obtained, from 24 of which only 7 in vitro studies on OSCC cell lines were included. Conclusions: From the preliminary data on the cellular lines of OSCC, it emerges that for oral cancer there are conditions for which the extracts of Punic granatum are effective at least from a prevention perspective.

Chronic hyperplastic candidiasis (CHC) is a prototypical oral lesion caused by chronic Candida infection. A major controversy surrounding CHC is whether this oral lesion owns malignant transformation (MT) potential. The aim of the present study was to evaluate current evidence on the MT of CHC and to determine the variables which have the greatest influence on cancer development. Bibliographical searches included PubMed, Embase, Web of Science, Scopus and LILACS. The cohort studies and case series used to investigate the MT of CHC were deemed suitable for inclusion. The quality of the enrolled studies was measured by the Joanna Briggs Institute scale. Moreover, we undertook subgroup analyses, assessed small study effects, and conducted sensitivity analyses. From 338 studies, nine were finally included for qualitative/quantitative analysis. The overall MT rate for CHC across all studies was 12.1% (95% confidential interval, 4.1–19.8%). Subgroup analysis showed that the MT rate increased when pooled analysis was restricted to poor quality studies. It remains complex to affirm whether CHC is an individual and oral, potentially malignant disorder according to the retrieved evidence. Prospective cohort studies to define the natural history of CHC and a consensus statement to clarify a proper set of diagnostic criteria are strongly needed. PROSPERO ID: CRD42022319572.

In recent decades, aquaculture techniques for soft corals have made remarkable progress in terms of conditions and productivity. Researchers have been able to obtain larger quantities of soft corals, thus larger quantities of biologically active metabolites, allowing them to study their biological activity in many pharmacological assays and even produce sufficient quantities for clinical trials. In this review, we summarize 201 secondary metabolites that have been identified from cultured soft corals in the era from 2002 to September 2022. Various types of diterpenes (eunicellins, cembranes, spatanes, norcembranes, briaranes, and aquarianes), as well as biscembranes, sterols, and quinones were discovered and subjected to bioactivity investigations in 53 different studies. We also introduce a more in-depth discussion of the potential biological effects (anti-cancer, anti-inflammatory, and anti-microbial) and the mechanisms of action of the identified secondary metabolites. We hope this review will shed light on the untapped potential applications of aquaculture to produce valuable secondary metabolites to tackle current and emerging health conditions.

Ultraviolet B (UVB) is one of the most important environmental factors that cause extrinsic aging through increasing intracellular reactive oxygen species (ROS) production in the skin. Due to its protective roles against oxidative stress, nuclear factor erythroid-2-related factor (NRF2) has been traditionally considered as a target for skin aging prevention. Here, we identified the extract of Prinsepiae Nux, a top-grade drug listed in Shen Nong Ben Cao Jing, as a potent NRF2 activator by high-throughput screening. A bioassay-guided fractionation experiment revealed that NRF2-activating components were concentrated in the 90% methanol (MP) fraction. MP fraction significantly increased the expression of NRF2 and HO-1 protein and upregulated HO-1 and NQO1 mRNA expression in HaCaT cells. Moreover, MP fraction pre-treatment dramatically reversed UVB-induced depletion of NRF2 and HO-1, accumulation of intracellular ROS, NF-κB activation, and the upregulation of pro-inflammatory genes. Finally, the qualitative analysis using UPLC-tandem mass spectroscopy revealed the most abundant ion peak in MP fraction was identified as α-linolenic acid, which was further proved to activate NRF2 signaling. Altogether, the molecular evidence suggested that MP fraction has the potential to be an excellent source for the discovery of natural medicine to treat/prevent UVB-induced skin damage.

Lonicerae japonicae flos (LJ) is an Asian traditional herb that is used as a dietary supplement, tea, and beverage to clear heat and quench thirst. However, no studies investigated its effect on activated human neutrophils, which played a crucial role in the bad prognosis of coronavirus disease of 2019 (COVID-19) patients by aggravating lung inflammation and respiratory failure. Herein, we evaluated the anti-inflammatory effect of LJ ethanol extract (LJEE) on human neutrophils activated by N-formyl-methionyl-leucyl-phenylalanine (fMLF). Our experimental results indicated that LJEE suppressed fMLF-activated superoxide anion (O2•−) generation, the expression of CD11b, and cell adhesion and migration, as well as the formation of neutrophil extracellular traps in human neutrophils. Further in-depth mechanical investigation revealed that pretreatment with LJEE accelerated the Ca2+ clearance, but did not affect the phosphorylation of mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt) in activated human neutrophils. In addition, LJEE displayed a dose-dependent reactive oxygen species (ROS) scavenger activity, which assisted its anti-inflammatory activity. From the bioassay-coupled chromatographic profile, chlorogenic acids were found to dominate the anti-inflammatory effects of LJEE. Moreover, LJ water extract (LJWE) demonstrated an interrupting effect on the severe acute respiratory syndrome coronavirus-2 spike protein (SARS-CoV-2-Spike)/angiotensin-converting enzyme 2 (ACE2) binding. In conclusion, the obtained results not only supported the traditional use of LJ for heat-clearance, but also suggested its potential application in daily health care during the COVID-19 pandemic.

Background: Italy has witnessed high levels of COVID-19 deaths, mainly at the elderly age. We assessed the comorbidity and the biochemical profiles of consecutive patients ≤65 years of age to identify a potential risk profile for death. Methods: We retrospectively analyzed clinical data from consecutive hospitalized-for-COVID-19 patients ≤65 years, who were died (593 patients) or discharged (912 patients) during February–December 2020. Multivariate logistic regression identified the mortality risk factors. Results: Overweight (adjusted odds ratio (adjOR) 5.53, 95% CI 2.07–14.76), obesity (adjOR 8.58, CI 3.30–22.29), dyslipidemia (adjOR 10.02, 95% CI 1.06–94.22), heart disease (adjOR 17.68, 95% CI 3.80–82.18), cancer (adjOR 13.28, 95% CI 4.25–41.51) and male sex (adjOR 5.24, 95% CI 2.30–11.94) were associated with death risk in the youngest population. In the older population (46-65 years of age), the overweight and obesity were also associated with the death risk, however at a lower extent: the adjORs varyied from 1.49 to 2.36 for overweight patients and from 3.00 to 4.07 for obese patients. Diabetes was independently associated with death only in these older patients. Conclusion: Overweight, obesity and dyslipidemia had a pivotal role in increasing young individuals’ death risk. Their presence should be carefully evaluated for prevention and/or prompt management of SARS-CoV2 infection in such high-risk patients to avoid the worst outcomes.

Since the worldwide spread of SARS-CoV-2 infection, the management of COVID-19 has been a challenge for healthcare professionals. Although the respiratory system has primarily been affected with symptoms ranging from mild pneumonia to acute respiratory distress syndrome, other organs or systems have also been targets of the virus. The mouth represents an important route of entry for SARS-CoV-2. Cells in the oral epithelium, taste buds, and minor and major salivary glands express cellular entry factors for the virus, such as ACE2, TMPRSS2 and Furin. This leads to symptoms such as deterioration of taste, salivary dysfunction, mucosal ulcers, before systemic manifestation of the disease. In this review we report and discuss the prevalence and socio-demographics of taste disturbances in COVID-19 patients, analysing the current international data. Importantly, we also take stock of the various hypothesized pathogenetic mechanisms and their impact on the reported symptoms. The literature indicated that COVID-19 patients frequently present with gustatory dysfunction, whose prevalence varies by country, age and sex. Furthermore, this dysfunction also has a variable duration in relation to the severity of the disease. The pathogenetic action is intricately linked to viral action which can be expressed in several ways. However, in many cases these are only hypotheses that need further confirmation.

In this series of two papers, the humidity sensing of a carbon nanotube (CNT) network-based material is transduced and studied through quartz crystal microbalance (QCM) measurements. To this aim, quartzes functionalized with different amounts of sensing material were realized, exposed to different humidity levels, and characterized. In this second paper, the experimental results are presented and discussed. The sensing mechanisms are elucidated exploiting the theory presented in the first paper of this series. The presented results show that the investigated material functionalization induces a large response of QCM to humidity in terms of resonant frequency even at low RH levels, with a sensitivity of about 12 Hz/%RH (at RH < 30% and room temperature and 10 ug of deposited SWCNT solution) and an increase in sensitivity in the high RH range typical of nanostructured film. Regarding the response in terms of motional resistance, a large response is obtained only at intermediate and high humidity levels, confirming that condensation of water in the film plays an important role in the sensing mechanism of nanostructured materials.

The etiopathogenetic mechanisms involving tumor genesis, including alteration of cell proliferation, apoptosis, invasion, migration, and death, may lead to alterations in microRNAs (miR) expression. The hypothesis is that with the presence in the literature of recent studies conducted on miR-196a and miR-196b, it is possible to clearly determine, by aggregating the results, whether miR-196 upregulation in head and neck squamous cell carcinoma (HNSCC) tissues can represent a prognostic biomarker of survival through hazard ratio (HR) analysis. The systematic review was conducted following the indications of the PRISMA, and four electronic databases were used (Science Direct, SCOPUS, PubMed, and Cochrane Central), with the addition of gray literature. Combinations of keywords were used, such as miR-196, miR-196 AND HNSCC, microRNA AND HNSCC, LSCC AND miR-196, OSCC AND miR-196, OPSCC AND miR-196, HSCC AND miR-196. The meta-analysis and trial sequential analysis (TSA) were performed using RevMan 5.41 software and Stata 13 (StataCorp, College Station, TX, USA) with the implementation of the R 4.2 software. This search identified 1593 reports and, at the end of the selection, five articles were inserted. The results of the meta-analysis report an aggregate HR for overall survival (OS), between the highest and lowest miR-196 expression of 1.67, 95% CI: [1.16, 2.49]. In this meta-analysis, we found that the forest plot is in favor of higher OS in HNSCC patients, compared with the control, with low miR-196 expression, correlating this data with a favorable prognosis, which indicated the potential role of this miRNA in strengthening the therapy sensitiveness of the HNSCC patients. Consequently, the present systematic review places itself, together with other systematic reviews on this topic, in a key role to the finding of Phase 3 clinical trials studies, in search for a prognostic model of miR-196 for HNSCC. In conclusion, with the limitations of the meta-analysis, it can be argued that miRs of the miR-196 family could be independent prognostic biomarkers of survival for HNSCC.

Photoplethysmographic (PPG) signals are mainly employed for heart rate estimation but are also fascinating candidates in the search for cardiovascular biomarkers. However, their high susceptibility to motion artifacts can lower their morphological quality and, hence, affect the reliability of the extracted information. Low reliability is particularly relevant when signals are recorded in a real-world context, during daily life activities. We aim to develop two classifiers to identify PPG pulses suitable for heart rate estimation (Basic-quality classifier) and morphological analysis (High-quality classifier). We collected wrist PPG data from 31 participants over a 24 h period. We defined four activity ranges based on accelerometer data and randomly selected an equal number of PPG pulses from each range to train and test the classifiers. Independent raters labeled the pulses into three quality levels. Nineteen features, including nine novel features, were extracted from PPG pulses and accelerometer signals. We conducted ten-fold cross-validation on the training set (70%) to optimize hyperparameters of five machine learning algorithms and a neural network, and the remaining 30% was used to test the algorithms. Performances were evaluated using the full features and a reduced set, obtained downstream of feature selection methods. Best performances for both Basic- and High-quality classifiers were achieved using a Support Vector Machine (Acc: 0.96 and 0.97, respectively). Both classifiers outperformed comparable state-of-the-art classifiers. Implementing automatic signal quality assessment methods is essential to improve the reliability of PPG parameters and broaden their applicability in a real-world context.

To date, therapeutic switches are performed to reduce and prevent toxicity, improve adherence, promote virological control, and save costs. Drug switches are a daily challenge in the management of people living with HIV (PLWH), especially in those with multiple comorbidities and on polypharmacy. The objectives of this prospective analysis were: (I) to evaluate the viro-immunological efficacy of BIC/FTC/TAF in a cohort of PLWH who switched to this regimen from any other previous, at the Infectious and Tropical Diseases Unit of the Padua University Hospital; (II) to assess the impact on body weight, lipids, and renal function parameters at week 48; and (III) to evaluate daily costs changes, adherence, and the rate and causes of discontinuation of the regimen. We included all adult PLWH who switched to BIC/FTC/TAF from 1 February 2020 to 31 October 2021. We collected demographic, clinical, and laboratory data at baseline and week 48 after the switch. In addition, the estimated cART-related cost changes over the follow-up period were calculated. Over the study period, 290 individuals who switched to BIC/FTC/TAF, 76.9% were males, with a median age of 52 years, and 94.8% had an undetectable baseline HIV viremia. After a median time of 35 days (IQR: 1–55), 41 (14.1%) individuals discontinued the regimen. Factors significantly associated with discontinuation were switching from dual regimens, and neurological disorders. At week 48, we detected a significant increase in body weight, BMI, CD4 T-cell count, and CD4/CD8 ratio, and a significant reduction in triglycerides and costs; all patients had undetectable HIV RNA. Our results showed that switching to BIC/FTC/TAF may favor slightly immunological recovery and cost saving (−4.2 EUR/day from baseline to week 48, equivalent to a mean saving of 1533 EUR/year/person). The reduction in triglycerides does not appear to be clinically relevant, even if statistically significant, nor do both the increase in body weight and BMI (+1 kg and +0.29 BMI, respectively) and the increase in CD4 T-cell count (+45 cells/mmc). Further studies are needed to confirm our results.

Background and Objectives: In the presence of a persistent endodontic lesion or endodontic failure, the alternative for the recovery of the dental element is endodontic retreatment or endodontic surgery, which consists in the surgical removal of the root apices with retrograde closure of the endodontium. The objective of this systematic review and meta-analysis was to provide an updated value of the Risk Ratio between the two types of treatment in order to offer to clinicians who propose a non-surgical endodontic retreatment or an endodontic surgery a direct comparison. Materials and Methods: The revision was performed according to PRISMA indications: three databases (PubMed, Scopus and Cochrane register) were consulted through the use of keywords relevant to the revision topic: surgical endodontic retreatment, endodontic retreatment, apicoectomy. This search produced 7568 records which, after eliminating duplicates and applying the inclusion and exclusion criteria, resulted in a total of seven included articles. The meta-analyses were conducted by applying fixed-effects models, given the low percentage of heterogeneity. In addition, trial sequency analysis (TSA) was performed for the analysis of the statistical power of the results and GRADE for the quality of the evidence. Results: The results of the meta-analyses’ data report an aggregate risk ratio (RR) between non-surgical endodontic retreatment and surgical endodontic retreatment of: 1.05 [0.74, 1.47] at one year of follow-up; RR 2.22 [1.45, 3.41] at two years of follow-up; an RR 1.08 [0.73 1.62] for a follow-up period of 3–4 years; and an RR 0.92 [0.53, 1.61] for a follow-up period of 8–10 years. Conclusions: The results of the present meta-analysis show that in the long term, the risk of failure is identical for the two groups, and there is only a slightly higher risk of failure for non-surgical endodontic retreatments, when only two years of follow-up are considered.

Analytical techniques play a fundamental role in heritage science. Among them, Particle Induced X-ray Emission (PIXE) and X-ray Fluorescence (XRF) techniques are widely used in many laboratories for elemental composition analysis. Although they are well-established, a strong effort is put on their upgrade, making them suitable for more and more applications. Over the years, at the INFN-LABEC (the laboratory of nuclear techniques for the environment and cultural heritage of the Italian National Institute of Nuclear Physics), the INFN-CHNet group, the network devoted to cultural heritage, has carried out many technological improvements to the PIXE and XRF set-ups for the analysis of works of art and archaeological finds. Among the many, we recall here the scanning external microbeam facility at the TANDEM accelerator and the MA-XRF scanner. The two instruments have shown complementary features: the former permits quantitative analysis of elements heavier than sodium, which is not possible with the latter in most of the case studies. On the contrary, the scanner has the undeniable advantage of portability, allowing it to work in situ. In this framework of technological developments in heritage science, INFN, CERN, and OPD are jointly carrying on the MACHINA (Movable Accelerator for Cultural Heritage In-situ Non-destructive Analysis) project for on-site Ion Beam Analysis (IBA) studies on cultural heritage.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide; in fact, it is among the top six neoplasms, with an incidence of about 370,000 new cases per year. The 5-year survival rate, despite chemotherapy, radiotherapy, and surgery for stages 3 and 4 of the disease, is low. MicroRNAs (miRNAs) are a large group of small single-stranded non-coding endogenous RNAs, approximately 18–25 nucleotides in length, that play a significant role in the post-transcriptional regulation of genes. Recent studies investigated the tissue expression of miR-155 as a prognostic biomarker of survival in HNSCC. The purpose of this systematic review is, therefore, to investigate and summarize the current findings in the literature concerning the potential prognostic expression of tissue miR-155 in patients with HNSCC. The revision was performed according to PRISMA indications: three databases (PubMed, Scopus, and the Cochrane Register) were consulted through the use of keywords relevant to the revision topic. Totally, eight studies were included and meta-analyzed. The main results report for the aggregate HR values of 1.40 for OS, 1.36 for DFS, and 1.09 for DPS. Finally, a trial sequencing analysis was also conducted to test the robustness of the proposed meta-analysis.

Fibrous dysplasia (FD) and hyperparathyroidism-jaw tumor syndrome (HPT-JT) are well-characterized benign bone fibro-osseous lesions. The intracellular mechanism leading to excessive deposition of fibrous tissue and alteration of differentiation processes leading to osteomalacia have not yet been fully clarified. Tissue Microarray (TMA)-based immunohistochemical expression of β-catenin, CK-AE1/AE3, Ki-67, cadherins and P-Runx2 were analyzed in archival samples from nine patients affected by FD and HPT-JT and in seven controls, with the aim of elucidating the contribution of these molecules (β-catenin, cadherins and P-Runx2) in the osteoblast differentiation pathway. β-catenin was strongly upregulated in FD, showing a hyper-cellulated pattern, while it was faintly expressed in bone tumors associated with HPT-JT. Furthermore, the loss of expression of OB-cadherin in osteoblast lineage in FD was accompanied by N-cadherin and P-cadherin upregulation (p < 0.05), while E-cadherin showed a minor role in these pathological processes. P-Runx2 showed over-expression in six out of eight cases of FD and stained moderately positive in the rimming lining osteoblasts in HPT-JT syndrome. β-catenin plays a central role in fibrous tissue proliferation and accompanies the lack of differentiation of osteoblast precursors in mature osteoblasts in FD. The study showed that the combined evaluation of the histological characteristics and the histochemical and immunohistochemical profile of key molecules involved in osteoblast differentiation are useful in the diagnosis, classification and therapeutic management of fibrous-osseous lesions.

The unmet need for specific anti-leukemic agents for the treatment of acute lymphoblastic leukemia led us to screen a variety of marine-derived bacteria. The fermentation broth extract of Streptomyces sp. LY1209 exhibited the most potent anti-proliferative effect against Molt 4 leukemia cells. A chromatographic anti-proliferative profiling approach was applied to characterize the metabolites with bioactive potential. Among all the metabolites, the major anti-leukemic constituents were staurosporine and a series of diketopiperazines (DKPs), including one novel and two known DKPs identified from nature for the first time. The structures of these compounds were identified using extensive spectroscopic analysis. The anti-proliferative potential of these metabolites against the Molt 4 cancer cell line was also determined. According to the in silico analysis utilizing a chemical global positioning system for natural products (ChemGPS-NP), it was suggested that these DKPs are potential anti-microtubule and alkylating agents, while staurosporine was proposed to be a tyrosine kinase inhibitor. Our findings not only identified a series of anti-proliferative metabolites, but also suggested a strategic workflow for the future discovery of natural product drug leads.

Among the first clinical symptoms of the SARS-CoV-2 infection is olfactory–gustatory deficit; this continues for weeks and, in some cases, can be persistent. We prospectively evaluated 162 patients affected by COVID-19 using a visual analogue scale (VAS) for nasal and olfactory–gustatory symptoms. Patients were checked after 7, 14, 21, 28, 90, and 180 days. A total of 118 patients (72.8%) reported an olfactory VAS < 7 at baseline (group B), and 44 (27.2%) reported anosmia (VAS ≥ 7) (group A) and underwent the Brief Smell Identification Test (B-SIT) and Burghart Taste Strips (BTS) to quantify the deficit objectively and repeated the tests to confirm the sense recovery. Group A patients showed B-SIT anosmia and hyposmia in 44.2% and 55.8% of cases, respectively. A total of 88.6% of group A patients reported ageusia with VAS ≥ 7, and BTS confirmed 81.8% of ageusia and 18.2% of hypogeusia. VAS smell recovery was recorded starting from 14 days, with normalization at 28 days. The 28-day B-SIT score showed normosmia in 90.6% of group A patients. The mean time for full recovery (VAS = 0) was shorter in group B (22.9 days) than in group A (31.9 days). Chemosensory deficit is frequently the first symptom in patients with COVID-19, and, in most cases, recovery occurs after four weeks.

Toll-like receptors (TLRs) regulate innate and adaptive immune responses. Moreover, TLRs can induce a pro-survival and pro-proliferation response in tumor cells. This study aims to investigate the expression of TLR4 in the epithelium surrounding oral squamous cell carcinomas (OSCC) in relation to its inflammatory microenvironment. This study included 150 human samples: 30 normal oral control (NOC), 38 non-lichenoid epithelium surrounding OSCC (NLE-OSCC), 28 lichenoid epithelium surrounding OSCC (LE-OSCC), 30 OSCC ex-non oral lichenoid lesion (OSCC Ex-NOLL), and 24 OSCC ex-oral lichenoid lesion (OSCC Ex-OLL). TLR4 expression was investigated by immunohistochemistry and the percentage of positive cells was quantified. In addition, a semiquantitative analysis of staining intensity was performed. Immunohistochemical analysis revealed that TLR4 is strongly upregulated in LE-OSCC as compared to normal control epithelium and NLE-OSCC. TLR4 expression was associated with the inflammatory environment, since the percentage of positive cells increases from NOC and NLE-OSCC to LE-OSCC, reaching the highest value in OSCC Ex–OLL. TLR4 was detected in the basal third of the epithelium in NLE-OSCC, while in LE-OSCC, TLR4 expression reached the intermediate layer. These results demonstrated that an inflammatory microenvironment can upregulate TLR4, which may boost tumor development.

SARS-CoV-2 can produce both severe clinical conditions and long-term sequelae, but data describing post-acute COVID-19 syndrome (PACS) are lacking for people living with HIV (PLWH). We aimed at assessing the prevalence and factors associated with severe COVID-19 and PACS in our cohort. We included all unvaccinated adult PLWH on antiretroviral treatment and plasma HIV-RNA < 40 cp/mL since at least six months before SARS-CoV-2 infection at the Infectious and Tropical Diseases Unit of Padua (Italy), from 20 February 2020 to 31 March 2021. COVID-19 severity was defined by WHO criteria; PACS was defined as the persistence of symptoms or development of sequelae beyond four weeks from SARS-CoV-2 infection. Demographic and clinical variables were collected, and data were analyzed by non-parametric tests. 123 subjects meeting the inclusion criteria among 1800 (6.8%) PLWH in care at the Infectious and Tropical diseases Unit in Padua were diagnosed with SARS-CoV-2 infection/COVID-19 during the study period. The median age was 51 years (40–58), 79.7% were males, and 77.2% of Caucasian ethnicity. The median CD4+ T-cell count and length of HIV infection were 560 cells/mmc (444–780) and 11 years, respectively. Of the patients, 35.0% had asymptomatic SARS-CoV-2 infection, 48% developed mild COVID-19, 17.1% presented moderate or severe COVID-19 requiring hospitalization and 4.1% died. Polypharmacy was the single independent factor associated with severe COVID-19. As for PACS, among 75 patients who survived SARS-CoV-2 symptomatic infection, 20 (26.7%) reported PACS at a median follow-up of six months: asthenia (80.0%), shortness of breath (50.0%) and recurrent headache (25.0%) were the three most common complaints. Only the severity of the COVID-19 episode predicted PACS after adjusting for relevant demographic and clinical variables. In our study, PLWH with sustained viral suppression and good immunological response showed that the risk of hospital admission for COVID-19 was low, even though the severity of the disease was associated with high mortality. In addition, the likelihood of developing severe COVID-19 and PACS was mainly driven by similar risk factors to those faced by the general population, such as polypharmacy and the severity of SARS-CoV-2 infection.

Evidence on the effectiveness of SARS-CoV-2 vaccines in nursing home (NHs) residents is limited. We examined the impact of the BNT162b2 mRNA SARS-CoV-2 vaccine on the course of the epidemic in NHs in the Florence Health District, Italy, before and after vaccination. Moreover, we assessed survival and hospitalization by vaccination status in SARS-CoV-2-positive cases occurring during the post-vaccination period. We calculated the weekly infection rates during the pre-vaccination (1 October–26 December 2020) and post-vaccination period (27 December 2020–31 March 2021). Cox analysis was used to analyze survival by vaccination status. The study involved 3730 residents (mean age 84, 69% female). Weekly infection rates fluctuated during the pre-vaccination period (1.8%–6.5%) and dropped to zero during the post-vaccination period. Nine unvaccinated (UN), 56 partially vaccinated (PV) and 35 fully vaccinated (FV) residents tested SARS-CoV-2+ during the post-vaccination period. FV showed significantly lower hospitalization and mortality rates than PV and UV (hospitalization: FV 3%, PV 14%, UV 33%; mortality: FV 6%, PV 18%, UV 56%). The death risk was 84% and 96% lower in PV (HR 0.157, 95%CI 0.049–0.491) and FV (HR 0.037, 95%CI 0.006–0.223) versus UV. SARS-CoV-2 vaccination was followed by a marked decline in infection rates and was associated with lower morbidity and mortality among infected NH residents.

Introduction: Tooth autotransplantation is the repositioning of an erupted, partially erupted, or non-erupted autologous tooth from one site to another within the same individual. Several factors influence the success rate of the autotransplant, such as the stage of root development, the morphology of the tooth, the surgical procedure selected, the extraoral time, the shape of the recipient socket, the vascularity of the recipient bed, and the vitality of the cells of the periodontal ligament. The aim of this scoping review was to provide the most up-to-date information and data on the clinical principles of the third-molar autograft and thus provide clinical considerations for its success. Materials and methods: This review was conducted based on PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews). The research was conducted by searching for keywords in three databases—PubMed, Scopus and Google Scholar—by two independent reviewers following the PRISMA protocol, from which 599 records were identified. Conclusions: Third-molar autotransplantation is a valid solution to replace missing teeth. The key to the success of this technique is the surgical procedure, which must be as atraumatic as possible to preserve the periodontal ligament of the tooth to be transplanted. The success rate is also linked to the stage of development of the root, with a worse prognosis in the case of a complete root.

Among botanical insecticides based on essential oils (EOs) or their main components, Carlina acaulis EO and the aromatic polyacetylene carlina oxide, constituting more than 90% of its EO, were recently proven to be effective against the larvae and adults of some insect vectors and pests. In this study, the toxicity of C. acaulis EO and carlina oxide were tested on Bactrocera oleae adults using a protein bait formulation. The LC50 values of the C. acaulis EO and carlina oxide were 706 ppm and 1052 ppm, respectively. Electroantennographic (EAG) tests on B. oleae adults showed that both carlina EO and oxide elicited EAG dose-dependent responses in male and female antennae. The responses to the EO were significantly higher than those to carlina oxide, indicating that other compounds, despite their lower concentrations, can play a relevant role. Moreover, Y-tube assays carried out to assess the potential attractiveness or repellency of carlina oxide LC90 to B. oleae adults showed that it was unattractive to both males and females of B. oleae, and the time spent by both sexes in either the control or the treatment arm did not differ significantly. Overall, this study points out the potential use of C. acaulis EO and carlina oxide for the development of green and effective “lure-and-kill” tools.

Background: Cone beam computed tomography (CBCT) is often used in different fields of dental science, especially in complex anatomical districts like the endodontic one. The aim of this study is to propose a low-dose CBCT protocol useful in cases of endodontic lesions. Methods: The device used was a MyRay Hyperion X9-11x5; the low dose setting of the machine was 90 Kv, 27 mAs, CTDI/Vol 2.89 mGy. The absorbed organ doses have been evaluated with an anthropomorphic phantom loaded with thermoluminescent dosimeters positioned at the level of sensitive organs like brain, bone marrow, salivary glands, thyroid, esophagus, oral mucosa, extrathoracic airways, and lymph nodes. Equivalent and effective doses have been calculated; the last one has been calculated using the recommendations approved by the Main Commission of ICRP (International Commission Radiological Protection) in March 2007. For the assessment of image quality, five senior clinicians, independent and experienced clinicians, were asked to state if CBCT scans were accurate enough to assess endodontic lesions. Results: The use of a low-dose CBCT acquisition produced the lowest organ dose (5.01 microSv) at the level of the esophagus. Image quality has been considered accurate enough for endodontic diagnostic needs. Conclusions: CBCT low-dose protocol can be used over the standard one in endodontic special cases because it provides a significantly lower radiation dose to the patients while ensuring good image quality. However, further studies are necessary to evaluate the opportunity of low-dose CBCT exams in endodontic clinical practice.

Detectors are a key feature of the contemporary scientific approach to cultural heritage (CH), both for diagnostics and conservation. INFN-CHNet is the network of the Italian National Institute of Nuclear Physics that develops and applies new instrumentation for the study of CH. This process results in both optimized traditional state-of-the-art and highly innovative detection setups for spectrometric techniques. Examples of the former are X-rays, gamma-rays, visible-light and particles spectrometers tailored for CH applications, with optimized performances, reliability, weight, transportability, cost, absorbed power, and complementarity with other techniques. Regarding the latter, examples are ARDESIA, the array of detectors at the DAΦNE-Light facility, the MAXRS detection setup at the Riken-RAL muon beamline and the imaging facilities at the LENA Laboratory. Paths for next-generation instruments have been suggested, as in the case of the X-ray Superconductive Detectors and X-ray Microcalorimeter Spectrometers, allowing astonishing improvement in energy resolution. Many issues in CH can now be addressed thanks to scientific techniques exploiting the existing detectors, while many others are still to be addressed and require the development of new approaches and detectors.

While cross-sectional imaging has seen continuous progress and plays an undiscussed pivotal role in the diagnostic management and treatment planning of patients with rectal cancer, a largely unmet need remains for improved staging accuracy, assessment of treatment response and prediction of individual patient outcome. Moreover, the increasing availability of target therapies has called for developing reliable diagnostic tools for identifying potential responders and optimizing overall treatment strategy on a personalized basis. Radiomics has emerged as a promising, still fully evolving research topic, which could harness the power of modern computer technology to generate quantitative information from imaging datasets based on advanced data-driven biomathematical models, potentially providing an added value to conventional imaging for improved patient management. The present study aimed to illustrate the contribution that current radiomics methods applied to magnetic resonance imaging can offer to managing patients with rectal cancer.