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Introduction and objective: Several studies have suggested that the hospitalization rate for COVID-19 in children and adolescents may reflect the prevalence of the infection rather than the severity of the disease. The aim of this study was to describe the clinical features of hospitalised paediatric patients with SARS-CoV-2 infection in order to understand if the infection was the reason for admission. Methods: Retrospective cohort study including patients aged 0–18 years with SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) admitted to a tertiary care children’s hospital in Spain between 01/01/2020 and 12/31/2021. Results: 228 patients were included, corresponding to 150 cases of COVID-related admission (SARS-CoV-2 infection as main cause of hospitalization) and 78 of non-COVID-related admission (SARS-CoV-2 infection unrelated to the hospitalization).In the group of COVID-related admissions, 58 patients had comorbidities. Forty-nine patients had acute respiratory disease (pneumonia, bronchospasm or bronchiolitis). Multisystem inflammatory syndrome in children was diagnosed in 27 and was significantly more frequent in the first year of the pandemic (wild type virus). Eighty percent of patients with acute respiratory disease needed respiratory support, mostly low-flow oxygen therapy. The severity of the disease was similar in all virus variants. Two patients (both with severe comorbidities) died from COVID-related conditions. Conclusions: In our study, one third of the patients were admitted with SARS-CoV-2 infection but not because of it. Acute respiratory disease was less frequent and had a better prognosis compared to the adult population, while MIS-C was a major cause of morbidity and hospitalization. The fatality rate was extremely low. Resumen: Introducción y objetivo: Varios estudios han sugerido que la tasa de hospitalización por COVID-19 en niños y adolescentes puede reflejar la prevalencia de la infección más que la gravedad de la enfermedad. El objetivo de este estudio fue describir las características clínicas de pacientes pediátricos hospitalizados con infección por SARS-CoV-2, con el fin de comprender si este fue el principal motivo de ingreso. Métodos: Estudio de cohortes retrospectivo que incluyó a pacientes de 0 a 18 años con infección por SARS-CoV-2 o síndrome inflamatorio multisistémico pediátrico vinculado a SARS-CoV-2 (SIM-PedS), ingresados en un hospital infantil de tercer nivel en España entre el 01/01/2020 y el 31/12/2021. Resultados: Se incluyeron 228 pacientes: 150 fueron ingresos causados por COVID (infección por SARS-CoV-2 como principal causa de hospitalización) y 78 fueron ingresos no causados por COVID (infección por SARS-CoV-2 no relacionada con la hospitalización). Entre los ingresos causados por COVID, 58 pacientes tenían comorbilidades. 49 pacientes cursaron con enfermedad respiratoria aguda (neumonía, broncoespasmo o bronquiolitis). 27 pacientes fueron diagnosticados de SIM-PedS; este diagnóstico se observó con más frecuencia durante el primer año de la pandemia (variante wild type). El 80% de los pacientes con enfermedad respiratoria aguda necesitaron algún tipo de soporte respiratorio, principalmente oxígeno de bajo flujo. La gravedad de la enfermedad fue similar con todas las variantes del virus. Dos pacientes (ambos con comorbilidades graves) fallecieron por afecciones relacionadas con la COVID-19. Conclusiones: En nuestro estudio, un tercio de los pacientes fueron hospitalizados con infección por SARS-CoV-2 pero no a causa de ella. La enfermedad respiratoria aguda tuvo menos incidencia y mejor pronóstico que en la población adulta, mientras que el SIM-PedS fue una causa importante de morbilidad y hospitalización. La mortalidad fue extremadamente baja.

The use of 3D-printed highly porous titanium acetabular cups in total hip arthroplasty (THA) is increasing. The porosity and mechanical properties of such highly porous titanium structures mimic those of natural cancellous bone, possibly allowing biological implant fixation to be improved. Recently, a 3D-printed highly porous Dual Mobility (DM) monobloc construct fully manufactured using Ti6Al4V alloy, with a titanium–niobium nitride (TiNbN) ceramic coating on the articular side to allow articulation against the mobile liner by improving the titanium vs. polyethylene tribological behavior, was introduced in THA. To the best of our knowledge, this is the first highly porous titanium monobloc DM implant on the market. The reasons for using a Ti alloy highly porous DM are multifarious: to prevent any possible adverse reactions due to the corrosion of Cobalt–Chromium–Molybdenum Alloy (CoCrMo) and Stainless Steel (SS) implants and to improve implant primary and secondary stability, particularly in cases of poor bone quality. Finally, with the introduction of an inner TiNbN ceramic coating surface, it was possible to overcome the poor tribological quality of titanium. Another interesting characteristic is this material’s higher implant radiolucency, which might facilitate the radiographic assessment of cup orientation, which can, in turn, facilitate the detection of any intraprosthetic dislocation (IPD) and the measurement of polyethylene wear, which is very important in the study of the durability of THA.

Star polymers, consisting of many arms connecting to a central core, represent a branched nanoscale material with compact structure and large surface area. Their synthesis is usually performed by making use of living polymers made by anionic polymerization as arms, and multifunctional compounds as linking agents. In general, polymer blends resulting from the star coupling process exhibit some polydispersity, which is influenced by (i) the polydispersity of the primary chains and (ii) the kinetics of the linking processes to the coupling agent. In the present contribution we develop a mathematical model for the description of the star coupling process in continuous reactors. The proposed model is based on the following statements: (i) the characterization of the MWD of the branched polymer species is accomplished by exploiting a probabilistic approach and (ii) the concentration of the single species is evaluated through implementation of mass balance equations, where the reactions describing the linking of the living polymers to the active branched unit are modelled with first and second order kinetics. The final goal is to predict the MWD shape when varying the operating conditions (i.e.: concentration of polymers and multifunctional agents in the feed flow and residence time).

Lung cancer is among the most clinically challenging tumors because of its aggressive proliferation, metastasis, and the presence of cancer stem cells (CSCs). Natural bioactive substances have been used for cancer prevention, and, in particular, resveratrol (RSV), a stilbene-based compound with wide biological properties, has been proposed for chemoprevention. Its lesser-known analogue 4,4’-dihydroxy-trans-stilbene (DHS) has demonstrated superior activity both in cell-based assays and in mouse and zebrafish in vivo models. The present study analyzed the effects of DHS and RSV on A549 lung cancer cells, with a particular focus on stemness features and CSCs, isolated by sorting of the side population (SP). The results show that both stilbenes, especially DHS, strongly inhibited cell cycle progression. A reduction in the S phase was induced by DHS, whereas an increase in this phase was obtained with RSV. In addition, 50% reductions in the clonogenicity and soft agar colony formation were observed with the DHS treatment only. Finally, both stilbenes, especially DHS, reduced stemness marker expression in A549 cells and their sorted SP fraction. Spheroid formation, higher in SP cells than in the main population (MP), was significantly reduced after pretreatment with DHS, which was found to decrease SOX2 levels more than RSV. These findings indicate that stilbenes, and particularly DHS, affect stemness features of A549 cells and the SP fraction, suggesting their potential utility as anticancer agents, either alone or combined with chemotherapeutic drugs.

Atherosclerotic disease of the carotid arteries is a crucial risk factor in predicting the likelihood of future stroke events. In addition, emerging studies suggest that carotid stenosis may also be an indicator of plaque load on coronary arteries and thus have a correlation with the risk of acute cardiovascular events. Furthermore, although in symptomatic patients the degree of stenosis is the main morphological parameter studied, recent evidence suggests, especially in asymptomatic patients, that plaque vulnerability should also be evaluated as an emerging and significant imaging parameter. The reference diagnostic methods for the evaluation of carotid stenosis are currently ultrasonography, magnetic resonance imaging (MRI), and computed tomography angiography (CTA). In addition, other more invasive methods such as 123I-metaiodobenzylguanidine (MIBG) scintigraphy and PET-CT, as well as digital subtraction angiography, can be used. Each method has advantages and disadvantages, and there is often some confusion in their use. For example, the usefulness of MRI is often underestimated. In addition, implementations for each method have been developed over the years and are already enabling a significant increase in diagnostic accuracy. The purpose of our study is to make an in-depth analysis of all the methods in use and in particular their role in the diagnostic procedure of carotid stenosis, also discussing new technologies.

Background and Objectives: Cellulite, or edemato-fibro-sclerotic panniculopathy (EFP), is characterized by dermal and hypodermal changes leading to adipose tissue accumulation and compromised venous circulation. This study investigates the efficacy of a hypertonic cream containing concentrated sodium chloride (Jovita Osmocell®) in addressing water retention and structural alterations in adipose tissue, aiming to interrupt the cellulite formation process. Materials and Methods: A 12-week, prospective, monocentric, double-blind, placebo-controlled study enrolled 30 female subjects with grade II or III cellulite. Patients were randomized to receive hypertonic cream or a placebo. Thigh circumference, ultrasound evaluations, and standardized photographs were collected at baseline, intermediate, and endpoint visits. Adverse events were monitored. Results: After 84 days, the hypertonic cream group exhibited a significant reduction in thigh circumference compared to the placebo group (p = 0.0037). B-mode ultrasound examinations revealed significant changes in the parameters studied, such as the thickness of the subcutaneous tissue. No statistically significant changes were noticed in the placebo group. Volunteers reported the investigational product’s pleasantness and good anti-cellulite activity, with no reported adverse events. Conclusions: The hypertonic cream demonstrated efficacy in reducing thigh circumference, addressing water retention and structural alterations in adipose tissue. The proposed mechanism involves osmosis, releasing accumulated fluids between fat cells, supporting drainage, and reducing inflammation. This study supports the efficacy and safety of hypertonic sodium chloride emulsions in cellulite treatment and confirms safety and user satisfaction.

BACKGROUND:Systemic and local immune suppression plays a significant role in glioma progression. Glioma microenvironment contains both brain-resident microglial cells (MG) and bone marrow-derived macrophages (BMDM), but the study of their functional and immune regulatory activity has been hampered until now by the lack of markers allowing a proper identification and isolation to collect pure populations. METHODS:Myeloid and lymphoid infiltrate were characterized in grade II, III and IV gliomas by multicolor flow cytometry, along with the composition of the cell subsets of circulating myeloid cells. Macrophages were sorted and tested for their immunosuppressive ability. Moreover, following preoperative administration of 5-aminolevulinic acid to patients, distinct areas of tumor lesion were surgically removed and analyzed, based on protoporphyrin IX fluorescence emission. RESULTS:The immune microenvironment of grade II to grade IV gliomas contains a large proportion of myeloid cells and a small proportion of lymphocytes expressing markers of dysfunctional activity. BMDM and resident MG cells were characterized through a combination of markers, thus permitting their geographical identification in the lesions, their sorting and subsequent analysis of the functional characteristics. The infiltration by BMDM reached the highest percentages in grade IV gliomas, and it increased from the periphery to the center of the lesion, where it exerted a strong immunosuppression that was, instead, absent in the marginal area. By contrast, MG showed little or no suppression. Functional differences, such as iron metabolism and phagocytosis, characterized resident versus blood-derived macrophages. Significant alterations in circulating monocytes were present in grade IV patients, correlating with accumulation of tumor macrophages. CONCLUSIONS:Grade IV gliomas have an alteration in both circulating and tumor-associated myeloid cells and, differently from grade II and III gliomas, show a significant presence of blood-derived, immune suppressive macrophages. BMDM and MG have different functional properties.

Lung cancer is among the most clinically challenging tumors because of its aggressive proliferation, metastasis, and the presence of cancer stem cells (CSCs). Natural bioactive substances have been used for cancer prevention, and, in particular, resveratrol (RSV), a stilbene-based compound with wide biological properties, has been proposed for chemoprevention. Its lesser-known analogue 4,4'-dihydroxy-trans-stilbene (DHS) has demonstrated superior activity both in cell-based assays and in mouse and zebrafish in vivo models. The present study analyzed the effects of DHS and RSV on A549 lung cancer cells, with a particular focus on stemness features and CSCs, isolated by sorting of the side population (SP). The results show that both stilbenes, especially DHS, strongly inhibited cell cycle progression. A reduction in the S phase was induced by DHS, whereas an increase in this phase was obtained with RSV. In addition, 50% reductions in the clonogenicity and soft agar colony formation were observed with the DHS treatment only. Finally, both stilbenes, especially DHS, reduced stemness marker expression in A549 cells and their sorted SP fraction. Spheroid formation, higher in SP cells than in the main population (MP), was significantly reduced after pretreatment with DHS, which was found to decrease SOX2 levels more than RSV. These findings indicate that stilbenes, and particularly DHS, affect stemness features of A549 cells and the SP fraction, suggesting their potential utility as anticancer agents, either alone or combined with chemotherapeutic drugs. [ABSTRACT FROM AUTHOR]

Abstract Objective To evaluate the role and the advantages of nasopharyngeal swabs in the detection of Influenza A and B viruses and Respiratory syncytial virus through a rapid test based upon a nucleic acid amplification reaction in order to avoid improper antibiotics use. Design Case-control retrospective study. Setting Emergency Room of “Sandro Pertini” General Hospital, Rome, Italy. Participants Children (

Abstract Background Communication between the gut microbiota and the brain is primarily mediated via soluble microbe-derived metabolites, but the details of this pathway remain poorly defined. Methylamines produced by microbial metabolism of dietary choline and l-carnitine have received attention due to their proposed association with vascular disease, but their effects upon the cerebrovascular circulation have hitherto not been studied. Results Here, we use an integrated in vitro/in vivo approach to show that physiologically relevant concentrations of the dietary methylamine trimethylamine N-oxide (TMAO) enhanced blood-brain barrier (BBB) integrity and protected it from inflammatory insult, acting through the tight junction regulator annexin A1. In contrast, the TMAO precursor trimethylamine (TMA) impaired BBB function and disrupted tight junction integrity. Moreover, we show that long-term exposure to TMAO protects murine cognitive function from inflammatory challenge, acting to limit astrocyte and microglial reactivity in a brain region-specific manner. Conclusion Our findings demonstrate the mechanisms through which microbiome-associated methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function. Video abstract

Atherosclerotic disease of the carotid arteries is a crucial risk factor in predicting the likelihood of future stroke events. In addition, emerging studies suggest that carotid stenosis may also be an indicator of plaque load on coronary arteries and thus have a correlation with the risk of acute cardiovascular events. Furthermore, although in symptomatic patients the degree of stenosis is the main morphological parameter studied, recent evidence suggests, especially in asymptomatic patients, that plaque vulnerability should also be evaluated as an emerging and significant imaging parameter. The reference diagnostic methods for the evaluation of carotid stenosis are currently ultrasonography, magnetic resonance imaging (MRI), and computed tomography angiography (CTA). In addition, other more invasive methods such as 123I-metaiodobenzylguanidine (MIBG) scintigraphy and PET-CT, as well as digital subtraction angiography, can be used. Each method has advantages and disadvantages, and there is often some confusion in their use. For example, the usefulness of MRI is often underestimated. In addition, implementations for each method have been developed over the years and are already enabling a significant increase in diagnostic accuracy. The purpose of our study is to make an in-depth analysis of all the methods in use and in particular their role in the diagnostic procedure of carotid stenosis, also discussing new technologies. [ABSTRACT FROM AUTHOR]

Dietary interventions, such as calorie restriction and ketogenic diet, have been extensively studied in ageing research, including in cognitive decline. Epidemiological studies indicate beneficial effects of certain dietary regimes on mental health, including mood disorders and dementia. However, randomised-controlled trials (the gold-standard of evidence-based medicine) on calorie restriction diets and the ketogenic diet have yet to show clinically convincing effects in neuropsychiatric disorders. This review will examine the quality of studies and evidence base for the ketogenic and calorie restriction diets in common neuropsychiatric conditions, collating findings from preclinical experiments, case reports or small clinical studies, and randomised controlled clinical trials. The major cellular mechanisms that mediate the effects of these dietary interventions on brain health include neuroinflammation, neuroprotection, and neuromodulation. We will discuss the studies that have investigated the roles of these pathways and their interactions. Popularity of the ketogenic and calorie restriction diets has grown both in the public domain and in psychiatry research, allowing for informed review of the efficacy, the limitations, and the side effects of these diets in specific patient populations. In this review we will summarise the clinical evidence for these diets in neuropsychiatry and make suggestions to improve clinical translation of future research studies.

To date very few studies with small sample size have compared peroral esophageal myotomy (POEM) with the current surgical standard of care, laparoscopic Heller myotomy (LHM), in terms of efficacy and safety, and no recommendations have been proposed.To investigate the efficacy and safety of POEM compared with LHM, for the treatment of achalasia.The databases of Pubmed, Medline, Cochrane, and Ovid were systematically searched between January 1, 2005 and January 31, 2015, with the medical subject headings (MeSH) and keywords "achalasia," "POEM," "per oral endoscopic myotomy," and "peroral endoscopic myotomy," "laparoscopic Heller myotomy" (LHM), "Heller myotomy."All types of study designs including adult patients with diagnosis of achalasia were selected. Studies that did not report the comparison between endoscopic and surgical treatment, experimental studies in animal models, single case reports, technical reports, reviews, abstracts, and editorials were excluded.The total number of included patients was 486 (196 in POEM group and 290 in LHM group).There were no differences between POEM and LHM in reduction in Eckardt score (MD = -0.659, 95% CI: -1.70 to 0.38, P = 0.217), operative time (MD = -0.354, 95% CI: -1.12 to 0.41, P = 0.36), postoperative pain scores (MD = -1.86, 95% CI: -5.17 to 1.44, P = 0.268), analgesic requirements (MD = -0.74, 95% CI: -2.65 to 1.16, P = 0.445), and complications (OR = 1.11, 95% CI: 0.5-2.44, P = 0.796). Length of hospital stay was significantly lower for POEM (MD = -0.629, 95% CI: -1.256 to -0.002, P = 0.049). There was a trend toward significant reduction in symptomatic gastroesophageal reflux rate in favors of LHM compared to POEM group (OR = 1.81, 95% CI: 1.11-2.95, P = 0.017).All included studied were not randomized. Furthermore all selected studies did not report the results of follow-up longer than 1 year and most of them included patients who were both treatment naive and underwent previous endoscopic or surgical interventions for achalasia.POEM represents a safe and efficacy procedure comparable to the safety profile of LHM for achalasia at a short-term follow-up. Long-term clinical trials are urgently needed.

Abstract Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells developing from myeloid progenitors, which are enriched in pathological conditions such as cancer, and are known to inhibit the functions of effector T cells. During aging, several changes occur both at the adaptive and innate immune system level, in a process defined as immunoscenescence. In particular, the low-grade inflammation state observed in the elderly appears to affect hematopoiesis. We previously demonstrated that the combination of GM-CSF and G-CSF drives the in vitro generation of bone marrow-derived MDSCs (BM-MDSCs) from precursors present in human bone marrow aspirates of healthy donors, and that these cells are endowed with a strong immune suppressive ability, resembling that of cancer-associated MDSCs. In the present work we investigated BM-MDSCs induction and functional ability in a cohort of pediatric versus elderly donors. To this aim, we analyzed the differences in maturation stages and ability to suppress T cell proliferation. We found that the ex vivo distribution of myeloid progenitors is similar between pediatric and elderly individuals, whereas after cytokine treatment a significant reduction in the more immature compartment is observed in the elderly. Despite the decreased frequency, BM-MDSCs maintain their suppressive capacity in aged donors. Taken together, these results indicate that in vitro induction of MDSCs from the BM is reduced with aging and opens new hypotheses on the role of age-related processes in myelopoiesis.

In an international theoretical framework relating to the challenges of digitalization on public sector communication, the article focuses on the open government process to present a historical review of the public sector communication as it has developed in Italy in the past thirty years. Definitions, reforms and the regulatory framework, structures and competences, different communication approaches and goals are collected here thanks to those "scholars' voices" which have fuelled the scientific debate on communication in public administrations since the 1990s. A diachronic approach is necessary in order to investigate the dynamic nature of the relationship between citizens and public sector organizations in a wider changing context and to further grasp the influence of digital technologies, with their impact on communication strategies and paradigms. The focus of the contribution is on the challenges that communication is facing in the new digital environment and in the contemporary scenario of open government. As the authors underline, the use of digital media is often seen as functional both to promoting a culture of transparency, openness and accessibility and to overcoming the traditional limits of the bureaucratic organizations, but there are some opportunities and risks to consider. So, the final part of the article offers a reflection on the consequences of digitalization. It introduces some key aspects of the contemporary debate on public sector communication in general and specifically in Italy, offering a critical discussion on those topics – new skills and professional profiles, training programmes, internal management, multichannel strategies, etc. - that are revealing their complexity in the new relational and organizational context.

The mechanisms that restore endothelial barrier integrity following inflammation-induced breaching are incompletely understood. Here the authors show that the CD31 immune receptor contributes to reestablishing vascular integrity via its effects on endothelial cell metabolism.

Abstract Background Multiple sclerosis (MS) is an autoimmune disease which results from the invasion of the brain by activated immune cells across the endothelial cells (ECs) of the blood-brain barrier (BBB), due to loss of immune self-tolerance. Many reports define the metabolic profile of immune cells in MS, however little is known about the metabolism of the BBB ECs during the disease. We aim to determine whether circulating factors in MS induce metabolic alterations of the BBB ECs compared to a healthy state, which can be linked with disruption of BBB integrity and subsequent immune cell extravasation. Methods and results In this report, we used an in vitro model to study the effect of sera from naïve-to-treatment, relapsing-remitting MS (RRMS) patients on the human brain microvascular endothelium, comparing effects to age/sex-matched healthy donor (HD) sera. Our data show that RRMS serum components affect brain endothelial cells by impairing intercellular tightness through the down-modulation of occludin and VE-cadherin, and facilitating immune cell extravasation through upregulation of intercellular adhesion molecules (ICAM-1) and P-glycoprotein (P-gp). At a metabolic level, the treatment of the endothelial cells with RRMS sera reduced their glycolytic activity (measured through the extracellular acidification rate-ECAR) and oxygen consumption rate (oxidative phosphorylation rate-OCR). Such changes were associated with the down-modulation of endothelial glucose transporter 1 (GLUT-1) expression and by altered mitochondrial membrane potential. Higher level of reactive oxygen species released from the endothelial cells treated with RRMS sera indicate a pro-inflammatory status of the cells together with the higher expression of ICAM-1, endothelial cell cytoskeleton perturbation (stress fibres) as well as disruption of the cytoskeleton signal transduction MSK1/2 and β-catenin phosphorylation. Conclusions Our data suggest that circulating factors present in RRMS patient serum induce physiological and biochemical alterations to the BBB, namely reducing expression of essential tightness regulators, as well as reduced engagement of glycolysis and alteration of mitochondrial potential. As these last changes have been linked with alterations in nutrient usage and metabolic function in immune cells; we propose that the BBB endothelium of MS patients may similarly undergo metabolic dysregulation, leading to enhanced permeability and increased disease susceptibility.

Background and Objectives: Cellulite, or edemato-fibro-sclerotic panniculopathy (EFP), is characterized by dermal and hypodermal changes leading to adipose tissue accumulation and compromised venous circulation. This study investigates the efficacy of a hypertonic cream containing concentrated sodium chloride (Jovita Osmocell®) in addressing water retention and structural alterations in adipose tissue, aiming to interrupt the cellulite formation process. Materials and Methods: A 12-week, prospective, monocentric, double-blind, placebo-controlled study enrolled 30 female subjects with grade II or III cellulite. Patients were randomized to receive hypertonic cream or a placebo. Thigh circumference, ultrasound evaluations, and standardized photographs were collected at baseline, intermediate, and endpoint visits. Adverse events were monitored. Results: After 84 days, the hypertonic cream group exhibited a significant reduction in thigh circumference compared to the placebo group (p = 0.0037). B-mode ultrasound examinations revealed significant changes in the parameters studied, such as the thickness of the subcutaneous tissue. No statistically significant changes were noticed in the placebo group. Volunteers reported the investigational product's pleasantness and good anti-cellulite activity, with no reported adverse events. Conclusions: The hypertonic cream demonstrated efficacy in reducing thigh circumference, addressing water retention and structural alterations in adipose tissue. The proposed mechanism involves osmosis, releasing accumulated fluids between fat cells, supporting drainage, and reducing inflammation. This study supports the efficacy and safety of hypertonic sodium chloride emulsions in cellulite treatment and confirms safety and user satisfaction. [ABSTRACT FROM AUTHOR]