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Abstract Background Primitive location of melanoma could be a relevant prognostic factor. As regards the scalp, some studies indicate a particularly aggressive biological behaviour for this anatomical localisation. Objectives In this multicentric study, data regarding head–neck melanoma (HNM) have been revised. Methods The design of the study included two main phases. In this retrospective study, data regarding HNM have been collected and analysed. Results In summary, our data suggest that the posterior neck is the area most affected by thicker melanomas. Cheeks and neck melanoma are associated with reduced disease‐free years of life and overall survival compared with all other sites of HNM. Conclusions This study provides useful information in defining the clinical features of HNM, thus improving diagnosis and treatment strategies.

Vulvar lichen sclerosus is a chronic inflammatory condition characterized by the thinning and atrophy of the skin and mucosa surrounding the vulva and anus. This study evaluates the efficacy of a treatment protocol utilizing blue-diode laser photobiomodulation in managing vulval lichen sclerosus symptoms in a cohort of 12 female patients. The treatment protocol consisted of laser sessions for 3 times a week for 2 weeks, and follow-up sessions over a 16-week period. Objective and subjective parameters were assessed before treatment, at the end of treatment, and at 4-month follow-up visits. Results demonstrated significant reductions in subjective symptoms such as itching and pain, as well as improvements in objective signs including erythema and fissures. No side effects were observed, indicating the safety and tolerability of laser treatment. These findings suggest that photobiomodulation can be an effective therapeutic option for patients with vulval lichen sclerosus, with future research aimed at refining treatment protocols and evaluating its long-term benefits.

Skeletal muscle secretome, through its paracrine and endocrine functions, contributes to the maintenance and regulation of overall physiological health. We conducted a narrative review on the role of skeletal muscle and exercise in maintaining glucose homeostasis, driving insulin resistance (IR), and preventing type 2 diabetes in pediatric populations, especially in the context of overweight and obesity. Myokines such as interleukin (IL)-6, IL-8, and IL-15, as well as irisin, myonectin, and myostatin, appear to play a crucial role in IR. Skeletal muscle can also become a target of obesity-induced and IR-induced inflammation. In the correlation between muscle, IR, and inflammation, the role of infiltration of the immune cells and the microvasculature may also be considered. It remains unclear which exercise approach is the best; however, combining aerobic exercise with resistance training seems to be the most effective strategy for managing IR, with high-intensity activities offering superior metabolic benefits and long-term adherence. Encouraging daily participation in enjoyable and engaging exercise is key for long-term commitment and effective glucose metabolism management. Promoting physical activity in children and adolescents must be a top priority for public health, not only in terms of individual quality of life and well-being but also for community health.

Background Overweight and obesity are defined as abnormal or excessive fat accumulation that presents a risk to health; and compared with their normal-weight peers, these individuals tend to have a lower level of self-confidence, and consequently lower physical activity adherence. Due to these self-perceived barriers, the aim of our study was to evaluate the efficacy of an online training program on self-reported physical fitness (SRPF) in children with obesity (OB). Methods A total of 32 children with OB carried out physical fitness (PF) tests and were asked to complete the International Fitness Enjoyment Scale (IFIS) questionnaire. The physical fitness tests were the Standing Broad Jump (SBJ), the 6-Min Walking Test (6MWT) and the 4 × 10 m sprint test. Children participated in a 3-weekly 60-min training session through Zoom platform. Before the beginning of the training protocol, OB children were compared with normal weight (NW) ones for PF batteries and the IFIS questionnaire. Changes in performances after the training were assessed by paired Student t and Wilcoxon tests. Results After the online training program children increased their performance in 6MWT (mean difference (MD) = 54.93; p < 0.0001) in SBJ (MD = 10.00; p = 0.0001) and in 4 × 10 m sprint test (MD = −0.78; p < 0.0001). No differences were found in children’s physical fitness perception. Discussion Our study highlighted how a structured online training program can lead to improvements in PF of children with OB. Instead, the lack of differences in SRPF after the training suggests interesting questions to be explored on the aspects linked to self-perception. Therefore, even if our training protocol could not directly improve SRPF in children with obesity, the enhancement of their PF could be a starting point for achieving this result with a longer training period and consequently improve PA participation for children with OB.

Background: From a young age, children learn different motor skills known as fundamental motor skills. The acquisition of these skills is crucial for the future development of context-tailored actions that could improve adherence to physical activity (PA) practice. Motor competence and function deficits have been associated with pediatric obesity. We reviewed the literature data regarding motor competence in pediatrics and impaired motor performance in children and adolescents with obesity. Methods: We assessed the abstracts of the available literature (n = 110) and reviewed the full texts of potentially relevant articles (n = 65) that were analyzed to provide a critical discussion. Results: Children and adolescents with obesity show impaired motor performance, executive functions, postural control, and motor coordination. Children’s age represents a crucial point in the development of motor skills. Early interventions are crucial to preventing declines in motor proficiency and impacting children’s PA and overall fitness levels. Conclusions: To involve children, the PA protocol must be fun and tailored in consideration of several aspects, such as clinical picture, level of physical fitness, and motor skills. A supervised adapted exercise program is useful to personalized PA programs from an early pediatric age.

Only 20% of children worldwide reach the suggested physical activity (PA) levels, and the COVID-19 restrictions seemed to have worsened this situation. In addition, physical fitness (PF) is a crucial marker of health and combined with PA could predict future health status. The aim of this study was to compare reported PA and PF levels in a sample of Italian adolescents. We administered the International PA Questionnaire and International Fitness Enjoyment Scale to 208 adolescents aged 16.0 ± 1.5 (N = 166 females, 16 ± 2.0 years) recruited from a high school in the province of Milan (Italy). The majority of the subjects were “Minimally active” but reported adequate PF levels. In particular, subjects who reported a “Very good” PF perception, had a lower PA level. The misperception of reported PA and PF from our sample could reduce the future PA level in adolescents and lead to a negative spiral of disengagement in PA. These findings should lead to more attention on and improvements to PA promotion in the adolescent population after the restrictions caused by the COVID-19 pandemic.

Although the important contribution of nutrition and physical activity to people’s health is known, it is equally well known that there are many barriers to adherence to healthy habits (i.e., of an organizational, economic, and/or psychological nature) experienced by the general population, as well as by people with non-communicable diseases. Knowledge of these barriers seems essential to the implementation of the activities and strategies needed to overcome them. Here, we aim to highlight the most frequent barriers to nutrition and exercise improvement that patients with chronic-degenerative diseases experience. Drawing from the Pubmed database, our analysis includes quantitative or mixed descriptive studies published within the last 10 years, involving adult participants with non-communicable diseases. Barriers of an organizational nature, as well as those of an environmental, economic, or psychological nature, are reported. The study of patients’ barriers enables healthcare and non-health professionals, stakeholders, and policymakers to propose truly effective solutions that can help both the general population and those with chronic pathologies to adhere to a healthy lifestyle.

Exergames are defined as digital games that require bodily movements to play, stimulating an active gaming experience to function as a form of physical activity (PA). The players interact with the game through whole-body movements improving energy expenditure. Exergames may be effective in improving physical and psychological aspects of children and adolescents with obesity. In this narrative review, we synthesized the current evidence regarding the role of exergames in modifying body composition and weight and in promoting changes in sedentary behavior to define the benefits of active video games as useful tools for fighting sedentarism and to outline the future directions of exergaming as a supplementation exercise rather than a replacement in educational programs for pediatric obesity. Data from the literature indicate that exergames may offer an interesting impact on childhood obesity and may be considered a potential strategy for controlling weight gain and body composition, promote PA, and decrease time spent on sedentary behavior in children and adolescents with obesity. However, exergame use also has some limits, such as children’s poor self-regulation and poor structuring of exergame use. Therefore, a prudent approach should be maintained, and additional high-quality research is needed to determine if exergames can be effectively used in the treatment of childhood obesity and if new digital media, as a supplementation of exercise rather than a replacement, could be considered to combat sedentary behavior in educational programs for pediatric obesity prevention.

The reconstruction of large segmental defects still represents a critical issue in the orthopedic field. The use of functionalized scaffolds able to create a magnetic environment is a fascinating option to guide the onset of regenerative processes. In the present study, a porous hydroxyapatite scaffold, incorporating superparamagnetic Fe3O4 nanoparticles (MNPs), was implanted in a critical bone defect realized in sheep metatarsus. Superparamagnetic nanoparticles functionalized with hyperbranched poly(epsilon-Lysine) peptides and physically complexed with vascular endothelial growth factor (VEGF) where injected in situ to penetrate the magnetic scaffold. The scaffold was fixed with cylindrical permanent NdFeB magnets implanted proximally, and the magnetic forces generated by the magnets enabled the capture of the injected nanoparticles forming a VEGF gradient in its porosity. After 16 weeks, histomorphometric measurements were performed to quantify bone growth and bone-to-implant contact, while the mechanical properties of regenerated bone via an atomic force microscopy (AFM) analysis were investigated. The results showed increased bone regeneration at the magnetized interface; this regeneration was higher in the VEGF-MNP-treated group, while the nanomechanical behavior of the tissue was similar to the pattern of the magnetic field distribution. This new approach provides insights into the ability of magnetic technologies to stimulate bone formation, improving bone/scaffold interaction.

Childhood obesity is characterized by an increased risk of several metabolic derangements including insulin resistance (IR). The strongest recommendations to prevent obesity and related complications are a balanced and adequate diet and practicing physical activity from early childhood. In this review, we propose to present the effects of healthy lifestyle strategies, including physical exercise and dietary approaches, on the management of IR and related metabolic derangements. All types of exercise (aerobic, resistance and combined training) effectively reduce IR in pediatric patients with obesity; it seems that aerobic and combined training stimulate greater improvements in IR compared to resistance training. Balanced normocaloric or hypocaloric dietary approaches are also valid strategies to address IR; it is not possible to assess the long-term impact of varying macronutrients on cardiometabolic risk. The glycemic index/load evaluation is a useful dietary approach to glucose metabolism control. Similarly, they should adopt the principle of the Mediterranean diet. Randomized studies with longer monitoring are needed to define the benefits of nutritional supplementation on IR. Considering that healthy style acquisition could track to later ages, programs of healthy lifestyle starting with children offer a better preventive strategy to preserve metabolic control and children’s health.

Background: Inflammatory bowel disease (IBD) patients show a higher risk of developing metabolic and cardiovascular diseases due to the presence of systemic low-grade chronic inflammation. Exercise can improve cardiovascular fitness and modulate the inflammatory processes. We evaluated the physical activity (PA) level and the fitness performance of children and adolescents with IBD. Patients and methods: We considered 54 pediatric patients with IBD (14.6 ± 2.2; 22 M), including CD (n = 27) UC (n = 24) and IBD unclassified (n = 3), and 70 healthy children. In all children, the Physical Activity Questionnaire (PAQ-C) and the International Fitness Enjoyment Scale were self-reported and recorded. Results: PAQ-C showed significant difference in PA levels in patients with IBD compared to controls (p < 0.001). A decrease in general fitness (p = 0.003), cardiorespiratory fitness (p = 0.002), strength (p = 0.01), speed agility (p = 0.003), and flexibility (p = 0.01) were also detected between patients and controls. Speed agility was related to age (p = 0.02) and BMI z-score (p = 0.01), and flexibility to BMI z-score (p = 0.05). We noted a correlation between PA levels and physician global assessment (p = 0.021) and activity disease severity (p = 0.025). Conclusions: A poorer PA level and poor physical competence were found in patients with IBD compared to healthy children and adolescents. Monitored exercise could provide multiple benefits at both physical and psychological levels.

BackgroundCutaneous melanoma (CM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CM in several Italian centers, which are part of the Clinical National Melanoma Registry (CNMR).MethodsMelanoma-specific survival and overall survival were calculated. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors.ResultsThe median follow-up time was 36 months (range 1.2-185.1). 787 CM were included in the analysis with completed information about therapies. All types of immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by anti-PD-1 (HR=0.25), globally immunotherapy was significantly associated with improved survival, either for anti-CTLA4 monotherapy or combined with anti-PD-1 (HR=0.47 and 0.26, respectively) and BRAFI+MEKI (HR=0.62).ConclusionsThe nivolumab/pembrolizumab in combination of ipilimumab and the addition of ant-MEK to the BRAFi can be considered the best therapies to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment.

During the refurbishing of the “Lombard Art of the XV-XVI century” department at the Pinacoteca di Brera (Milan), concluded in 2018, the Conservation and Restoration Center “La Venaria Reale” had the opportunity to study and restore the famous pictorial cycle of Men at Arms by Donato Bramante (1488-89). The paper aims to present the methodological approach and the results obtained with the last conservation treatment, aimed at a new and updated aesthetic proposal for the pictorial cycle. The main objective was to re-establish the unity of the images, compromised by the numerous lacunae left visible by previous treatments, respecting at the same time the material features of the paintings and the evidence of their particular conservative history. The interdisciplinary work group* has reconstructed the complex conservative history of the detached wall paintings, thanks to the technical observation of the surfaces and the scientific characterization of the constituent materials. The results were compared with the available historical documentation, in particular with historical photographs. The project allowed us to retrace the profound changes that the concept of pictorial integration has encountered over time, from the beginning of the twentieth century to the present day. The conservation treatment also originated from the need of the Pinacoteca di Brera to update the aesthetic presentation of the works, facilitating the reading of the fragmented images due to numerous lacunae. d images due to numerous lacunae.

Background: Physical fitness (PF) is positively related to skeletal and metabolic health, and it had an inverse relation with obesity. Adolescents with obesity have the worst performance in PF and speed-agility (SA) that contributes to an augmented risk to develop pathologies. To the best of our knowledge, many studies analyzed the trends of obesity and SA separately, but there is a lack of data about SA ability trends in adolescents with obesity. We aimed to investigate SA trends in children with obesity in the last few decades to define the association between body weight and physical performance. Methods: We recruited 3.923 Caucasian children across the period 1985–2010 in the same school in Northern Italy, near Milan. Once a year, at the ages of 11–12- and 13-years-old, we collected anthropometric measures and SA performance. We pooled the data into 5-year-period study waves and then stratified our analysis into test-sex-age BMI-z-score specific groups. Results: We reported an undetermined trend across years. The 4×5 m run test significantly decreased in adolescents with overweight/obesity, while we did not report a decline in 30 m and 60 m run tests. Conclusions: Fitness tests highlighted differences in normal weight compared to overweight/obese children, suggesting that it is crucial to carefully monitor PF capacities through the years.

In this study, we compared the overall gene and pathway expression profiles of HS-5 and HS-27A stromal cell lines with those of primary bone marrow MSCs to verify if they can be considered a reliable alternative tool for evaluating the contribution of MSCs in tumor development and immunomodulation. Indeed, due to their easier manipulation in vitro as compared to primary MSC cultures, several published studies took advantage of stromal cell lines to assess the biological mechanisms mediated by stromal cells in influencing tumor biology and immune responses. However, the process carried out to obtain immortalized cell lines could profoundly alter gene expression profile, and consequently their biological characteristics, leading to debatable results. Here, we evaluated the still undisclosed similarities and differences between HS-5, HS-27A cell lines and primary bone marrow MSCs in the context of tumor development and immunomodulation. Furthermore, we assessed by standardized immunological assays the capability of the cell lines to reproduce the general mechanisms of MSC immunoregulation. We found that only HS-5 cell line could be suitable to reproduce not only the MSC capacity to influence tumor biology, but also to evaluate the molecular mechanisms underlying tumor immune escape mediated by stroma cells. However, HS-5 pre-treatment with inflammatory cytokines, that normally enhances the immunosuppressive activity of primary MSCs, did not reproduce the same MSCs behavior, highlighting the necessity to accurately set up in vitro assays when HS-5 cell line is used instead of its primary counterpart.

The home advantage (HA) affects football competitions, especially due to the presence of crowd support. Even though several studies demonstrated that HA (which is influenced by the crowd) decreased in recent years, the empty stadia caused by COVID-19 restrictions offered unique situations to explore and quantify HA. For this reason, we aimed to assess HA in two seasons of the major Italian Championships. We conducted an observational study with the data from the last three seasons of the Italian football championship A–B series, analyzing a total of 2.964 individual game scores. To quantify the HA, the number of points won at home was calculated as a percentage of the total number of points won, home and away. In every season and for every team classification, HA was found (scored points > 50% in home matches). We reported a difference in HA median score for Serie B. Additionally, a difference was found in Serie A for middle-ranking HA median scores in the two seasons compared (p-value = 0.017), which was similarly found in Serie B (p-value = 0.009). The number of penalties was lower in the season with a crowd compared to one without a crowd (p = 0.001). The HA did not disappear in empty stadiums, so there must be other contributing factors. Additionally, we found that the referees were biased by the presence of the crowd in favor of the home teams, and this result could be considered by the football association during referees’ training and formation.

The coexistence of childhood obesity (or its risk) and COVID-19 pandemic put children and adolescents in greater risk to develop respiratory and cardiovascular diseases. In fact, the restrictions introduced to limit the spread of the virus had detrimental effects on various lifestyle components, especially in young population. This resulted in augmented levels of physical inactivity and sedentary behaviors and a reduced time spent in play outdoors or sport practices. Contrariwise, the increased use of technology led clinicians, teachers, and trainers to maintain relations with obese children/adolescents so as to reduce sedentary behaviors and the associated health risks. This narrative review aims to describe the role of Telehealth and Tele-exercise as useful tools in the management of pediatric obesity during COVID-19 pandemic. Telehealth and Tele-exercise were effective in promoting self-monitoring and behavioral changes, including adherence to exercise training programs in children and adolescents. Moreover, tele-exercise platforms such as applications or exergames allowed flexible scheduling, limiting the infection risks.

Mesenchymal stromal cells (MSCs) are adult, multipotent cells of mesodermal origin representing the progenitors of all stromal tissues. MSCs possess significant and broad immunomodulatory functions affecting both adaptive and innate immune responses once MSCs are primed by the inflammatory microenvironment. Recently, the role of extracellular vesicles (EVs) in mediating the therapeutic effects of MSCs has been recognized. Nevertheless, the molecular mechanisms responsible for the immunomodulatory properties of MSC-derived EVs (MSC-EVs) are still poorly characterized. Therefore, we carried out a molecular characterization of MSC-EV content by high-throughput approaches. We analyzed miRNA and protein expression profile in cellular and vesicular compartments both in normal and inflammatory conditions. We found several proteins and miRNAs involved in immunological processes, such as MOES, LG3BP, PTX3, and S10A6 proteins, miR-155-5p, and miR-497-5p. Different in silico approaches were also performed to correlate miRNA and protein expression profile and then to evaluate the putative molecules or pathways involved in immunoregulatory properties mediated by MSC-EVs. PI3K-AKT signaling pathway and the regulation of actin cytoskeleton were identified and functionally validated in vitro as key mediators of MSC/B cell communication mediated by MSC-EVs. In conclusion, we identified different molecules and pathways responsible for immunoregulatory properties mediated by MSC-EVs, thus identifying novel therapeutic targets as safer and more useful alternatives to cell or EV-based therapeutic approaches.

Necrotizing sialometaplasia is a rare, benign, self-limiting, necrotizing process involving the minor salivary glands, mainly the mucoserous glands of the hard palate. It is thought to be the result of an ischemic event of the vasculature supplying the salivary gland lobules. Some predisposing factors such as smoking, use of alcohol, denture wearing, recent surgery, traumatic injuries, respiratory infections, systemic diseases bulimia, and anorexia have been described. Herein we present a case of necrotizing sialometaplasia of the hard palate in a patient without known predisposing factors, in our opinion, resulting from the use of topical anti-inflammatory drug. After diagnosis, the patient underwent treatment with chlorhexidine gluconate and a full palatal acrylic guard to protect the exposed bone from food residues during meals. After the sixth week the lesion regressed.

In a time in which everybody’s asked a big effort to use hospitals, resources and emergency departments in a rational way, the Centralization – that is sending the right patient to the right hospital at the right time – allows an optimization of the resources and a better management of medical patients. In this study we examined the actual state of Centralization in the city of Ferrara where an experimental protocol of “centralization” has been introduced. This study has the purpose of simulating reality if the protocol had been introduced in the years 2008/2009. The results confirm not only that an important number of patients that were meant to be sent to the CTZ of Ferrara where instead sent to the PST but also that, on the contrary, patients from the suburbs that didn’t require advanced treatments were sent to the Sant’Anna hospital of Ferrara. So if medical literature already points out the advantages of a correct Centralization for patients with polytraumas; the study, based on the reality in Ferrara , shows how the creation of an agreed protocol with the goal to guide health workers at sending polytrauma patients to the right destination , instead of creating an excessive flow th the main hub, can improve the overall organization of health services, with an equal distribution between hub and spoke. When considering First Aid not always speed and rapidity guarantee survival; this is so much more real in the case of patients with polytrauma, where quality of cures assumes more importance than time.