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Background: Asthma is a chronic inflammatory disease that is very common among youth worldwide. The burden of this illness is very high not only considering financial costs but also on emotional and social functioning. Guidelines and many researches recommend to develop a good communication between physicians and children/caregiver and their parents. Nevertheless, a previous Italian project showed some criticalities in paediatric severe asthma management. The consensus gathered together experts in paediatric asthma management, experts in narrative medicine and patient associations with the aim of identify simple recommendation to improve communication strategies. Methods: Participants to the consensus received the results of the project and a selection of narratives two weeks before the meeting. The meeting was structured in plenary session and in three working groups discussing respectively about communication strategies with children, adolescents and parents. The task of each working group was to identify the most effective (DO) and least effective practices (DON' T) for 5 phases of the visit: welcome, comprehension of the context, emotions management, duration and end of the visit and endurance of the relationship. Results: Participants agreed that good relationships translate into positive outcomes and reached consensus on communication strategies to implement in the different phase of relationships. Conclusions: The future challenges identified by the participants are the dissemination of this Consensus document and the implementation of effective communication strategies to improve the management of pediatric asthma. [ABSTRACT FROM AUTHOR]

The literature highlights a complex array of risk factors associated with violent recidivism of sexual offenders. This study aimed to examine the risk of future violence among eight sex offenders within a detention facility in southern Italy. This was achieved through an exploration of various cognitive, emotional, and social factors, with the aim of identifying strategies for risk prevention and offering tailored recommendations for the management of violent recidivism risk. Evaluations involved evaluative-psychological interviews, review of psychological reports from their prison observation period, court documents, and comprehensive analysis of each subject’s psychosocial functioning and history of violent behaviour. Factors such as delinquent culture, family poverty, lack of parental figures, and conflicted family relationships were identified as influential in the life histories of these individuals. Additionally, early involvement in criminal activities, unstable emotional bonds, and deficiencies in education and relationships were seen as contributing factors to sexually deviant behaviour, including coercion and physical violence. [ABSTRACT FROM AUTHOR]

Recently, we proposed a Good Manufacturing Practice (GMP)-compliant production process for freeze-dried mesenchymal stem cell (MSC)-secretome (lyo-secretome): after serum starvation, the cell supernatant was collected, and the secretome was concentrated by ultrafiltration and freeze-dried, obtaining a standardized ready-to-use and stable powder. In this work, we modified the type of human platelet lysate (HPL) used as an MSC culture supplement during the lyo-secretome production process: the aim was to verify whether this change had an impact on product quality and also whether this new procedure could be validated according to GMP, proving the process robustness. MSCs were cultured with two HPLs: the standard previously validated one (HPL-E) and the new one (HPL-S). From the same pool of platelets, two batches of HPL were obtained: HPL-E (by repeated freezing and thawing cycles) and HPL-S (by adding Ca-gluconate to form a clot and its subsequent mechanical wringing). Bone marrow MSCs from three donors were separately cultured with the two HPLs until the third passage and then employed to produce lyo-secretome. The following indicators were selected to evaluate the process performance: (i) the lyo-secretome quantitative composition (in lipids and proteins), (ii) the EVs size distribution, and (iii) anti-elastase and (iv) immunomodulant activity as potency tests. The new HPL supplementation for MSCs culture induced only a few minimal changes in protein/lipid content and EVs size distribution; despite this, it did not significantly influence biological activity. The donor intrinsic MSCs variability in secretome secretion instead strongly affected the quality of the finished product and could be mitigated by concentrating the final product to reach a determined protein (and lipid) concentration. In conclusion, the modification of the type of HPL in the MSCs culture during lyo-secretome production induces only minimal changes in the composition but not in the potency, and therefore, the new procedure can be validated according to GMP. [ABSTRACT FROM AUTHOR]

In this paper, the experimental conditions for preparing ampicillin-loaded surfactant vesicles (SVs) are described. Our studies are focused on the potential use of a vesicular polymeric dispersion as ampicillin delivery system for topical application. The main components of the formulation are uncharged and charged SVs loaded with ampicillin and dispersed in a gellan solution. The following issues are addressed: the drug encapsulation efficiency (e.e.), the kinetic of drug release from the delivery systems, the antimicrobial activity of vesicle-entrapped ampicillin. The in vitro permeation experiments through a synthetic lipophilic barrier (Silastic™) and through porcine skin are carried out to evaluate the potential use as a dermal formulation. The use of both a synthetic and a biological membrane allows to discriminate between the effects related to variations of thermodynamic parameters and those correlated to biological factors. The release rate of ampicillin is increased by encapsulation in neutral and negatively charged SVs and the permeation rate was slowed by dispersion of drug-loaded SVs in gellan solution. Finally, studies of antimicrobial activity on prepared systems evidenced that ampicillin encapsulated in SVs exhibit a higher activity than the free drug. [Copyright &y& Elsevier]

Current literature regarding systemic autoimmune diseases in X‐chromosome aneuploidies is scarce and limited to case reports. Our aim was to evaluate the frequency of anti‐nuclear (ANAs), extractable nuclear (ENA), anti‐double‐stranded DNA (dsDNAs), anti‐smooth muscle (ASMAs) and anti‐mitochondrial (AMAs) antibodies in a large cohort of adults with Klinefelter's syndrome (KS, 47,XXY) and rare higher‐grade sex chromosome aneuploidies (HGAs) for the first time. Sera from 138 X‐chromosome aneuploid patients [124 adult patients with 47,XXY KS and 14 patients with HGA (six children, eight adults)] and 50 age‐matched 46,XY controls were recruited from the Sapienza University of Rome (2007–17) and tested for ANAs, ENAs, anti‐dsDNAs, ASMAs and AMAs. Non‐organ‐specific immunoreactivity was found to be significantly higher in patients with 47,XXY KS (14%) than in the controls (2%, p = 0.002). Among all the antibodies investigated, only ANAs were observed significantly more frequently in patients with 47,XXY KS (12.1%) than in the controls (2%, p = 0.004). No anti‐dsDNA immunoreactivity was found. Stratifying by testosterone replacement therapy (TRT), non‐organ‐specific autoantibody frequencies were higher in TRT‐naive (p = 0.01) and TRT‐treated groups than in controls. No patients with HGA were found positive for the various autoantibodies. Non‐organ‐specific autoantibodies were significantly present in 47,XXY adult patients. Conversely, HGAs did not appear to be target of non‐organ‐specific immunoreactivity, suggesting that KS and HGAs should be considered as two distinct conditions. The classification and diagnosis of systemic autoimmune diseases is frequently difficult. To support a correct clinical evaluation of KS disease and to prevent eventual secondary irreversible immune‐mediated damages, we highlight the importance of screening for non‐organ‐specific autoimmunity in Klinefelter's syndrome. [ABSTRACT FROM AUTHOR]

Aims: Our observational study aimed to evaluate the impact of the lockdown period due to 2019 Coronavirus disease pandemic on glycaemic control in a cohort of paediatric patients with type 1 diabetes (T1D).Methods: Eighty-five patients with T1D aged 5-18 years using continuous glucose monitoring (CGM) systems were enrolled. Demographic and clinical data, including glucose metrics generated by CGM-specific web-based cloud platforms, were collected in three different periods (pre-lockdown phase, lockdown phase, and post-lockdown phase) of 90 days each and were statistically analysed.Results: During the lockdown period, a clear improvement in almost all CGM metrics (time in range, time above range, coefficient of variation, and glucose management indicator) was observed in our study population, regardless of age and insulin type treatment. In the months following lockdown, maintaining satisfactory diabetes outcomes was confirmed only in younger patients (aged 5-9 years) and in those individuals on hybrid closed loop therapy.Conclusions: The increasing use of innovative technological devices together with data sharing systems and interaction with multidisciplinary diabetes team through telemedicine allowed paediatric patients with T1D to improve glucose metrics during the lockdown period. However, our findings showed that the achievement of better glycaemic control was transient for most patients. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathies are characterized by serum monoclonal component (MC) plus an intact immunoglobulin and a free light chain (FLC), or a combination of both. The measurement of FLC with Freelite® is the standard practice recommended by International Myeloma Working Group guidelines. Recently, Hevylite® heavy/light chains (HLC) assays were introduced to specifically target junctional epitopes between the heavy and light chains of intact immunoglobulins, allowing the independent quantification of the involved (MC) and uninvolved (polyclonal immunoglobulin background) HLC isotype. Between January 2012 and March 2014, 90 patients were examined: 49 multiple myeloma (MM), 6 smoldering MM (SMM) and 35 monoclonal gammopathy of undetermined significance (MGUS). Of these 90 patients, 300 samples were collected at different times. The diagnostic and monitoring contribution of Hevylite A and G assays was assessed in all 90 patients examined. Additionally, 3 representative cases were selected. The Hevylite absolute values and ratio demonstrated high sensitivity and specificity with respect to serum protein electrophoresis and serum immunofixation. The combined use of Hevylite A and G with Freelite was particularly useful in dubious cases with more than one MC or with co-migrating components, as well as in the course of monitoring to assess the independent change of FLC and HLC, possibly reflecting the presence of clonal heterogeneity in the cohort. From this study, it can be concluded that FLC and HLC are independent, useful markers to monitor the MC and to assess with greater specificity and sensitivity the effect of therapy, thereby providing clinical support. Further studies are required to assess the prognostic potential of Hevylite in MGUS and SMM. [ABSTRACT FROM AUTHOR]

Background aims. Mesenchymal stromal cells (MSC) are ideal candidates for regenerative and immunomodulatory therapies. The use of xenogeneic protein-free Good Manufacturing Practice-compliant growth media is a prerequisite for clinical MSC isolation and expansion. Human platelet lysate (HPL) has been efficiently implemented into MSC clinical manufacturing as a substitute for fetal bovine serum (FBS). Because the use of human-derived blood materials alleviates immunologic risks but not the transmission of blood-borne viruses, the aim of our study was to test an even safer alternative than HPL to FBS: HPL subjected to pathogen inactivation by psoralen (iHPL). Methods. Bone marrow samples were plated and expanded in oc-minimum essential medium with 10% of three culture supplements: HPL, iHPL and FBS, at the same time. MSC morphology, growth and immunophenotype were analyzed at each passage. Karyotype, tumorigenicity and sterility were analyzed at the third passage. Statistical analyses were performed. Results. The MSCs cultivated in the three different culture conditions showed no significant differences in terms of fibroblast colony-forming unit number, immunophenotype or in their multipotent capacity. Conversely, the HPLViHPL-MSCs were smaller, more numerous, had a higher proliferative potential and showed a higher Oct-3/4 and NANOG protein expression than did FBS-MSCs. Although HPLV iHPL-MSCs exhibit characteristics that may be attributable to a higher primitive sternness than FBS-MSCs, no tumorigenic mutations or karyotype modifications were observed. Conclusions. We demonstrated that iHPL is safer than HPL and represents a good, Good Manufacturing Practice-compliant alternative to FBS for MSC clinical production that is even more advantageous in terms of cellular growth and sternness. [ABSTRACT FROM AUTHOR]

Abstract: In this work, we report the preparation, the characterization and interaction with cells of novel pH-sensitive non-phospholipid vesicle formulations, from a non-ionic surfactant mixed with cholesterol (CHOL) and his derivative cholesteryl hemisuccinate (CHEMS), as pH-sensitive molecule. This molecule, can destabilize the vesicle lipid bilayer when exposed to an acidic environment, with a subsequent release of vesicular content, enhancing the cytoplasmatic delivery of drugs to target cells. Vesicles were characterized by static and dynamic light scattering, in order to evaluate their dimensions, bilayer thickness and vesicle stability. Membrane permeability changes were determined by the release of entrapped hydroxypyrene-1,3,6-trisulfonic acid (HPTS). Also diphenylhesatriene (DPH) fluorescence anisotropy and ζ potential measurements were used to evidence the pH sensitivity. Furthermore vesicles were characterized by means of electronic microscopy after freeze-fracture. The interaction of non-lipid vesicles containing different fluorescent dyes with Raw 264.7, mouse monocite macrophage, were analyzed by flow cytometric analysis. The obtained results indicate that the pH-sensitive vesicular structures show good plasma stability and relevant pH-sensitivity. Moreover this formulation was able to interact with target membranes (i.e. plasma or endosomal membrane) and to release the encapsulated material into the cytoplasm. [Copyright &y& Elsevier]

Fibroblast growth factor 10 is a novel member of the fibroblast growth factor family, which is involved in morphogenesis and epithelial proliferation. It is highly homologous to the keratinocyte growth factor (or fibroblast growth factor 7), a key mediator of keratinocyte growth and differentiation. Both fibroblast growth factor 10 and keratinocyte growth factor bind with high affinity to the tyrosine kinase keratinocyte growth factor receptor. Here we analyzed the effect of fibroblast growth factor 10 on primary cultures of human keratinocytes, grown in chemically defined medium, and we compared the proliferative and differentiative cell responses to fibroblast growth factor 10 with those induced by keratinocyte growth factor and epidermal growth factor. Cell counting, 5-bromo-2′-deoxyuridine incorporation, and western blot analysis showed that fibroblast growth factor 10, similarly to keratinocyte growth factor, not only is a potent mitogen for human keratinocytes, but also promotes the expression of both early differentiation markers K1 and K10 and late differentiation marker filaggrin in response to the Ca2+ signal, and seems to sustain the proliferative activity in suprabasal stratified cells. Immunoprecipitation/western blot analysis revealed that fibroblast growth factor 10, similarly to keratinocyte growth factor, is able to induce tyrosine phosphorylation of keratinocyte growth factor receptor and of cellular substrates such as PLCγ. [ABSTRACT FROM AUTHOR]

Background: Mantle cell lymphoma (MCL) has the worst prognosis of B-cell subtypes owing to its aggressive clinical disease course and incurability with standard chemo-immunotherapy. Options for relapsed MCL are limited, although several single agents have been studied. Lenalidomide is available in Italy for patients with MCL based on a local disposition of the Italian Drug Agency., Subjects, Materials, and Methods: An observational retrospective study was conducted in 24 Italian hematology centers with the aim to improve information on effectiveness and safety of lenalidomide use in real practice., Results: Seventy patients received lenalidomide for 21/28 days with a median of eight cycles. At the end of therapy, there were 22 complete responses (31.4%), 11 partial responses, 6 stable diseases, and 31 progressions, with an overall response rate of 47.1%. Eighteen patients (22.9%) received lenalidomide in combination with either dexamethasone ( n  = 13) or rituximab ( n  = 5). Median overall survival (OS) was reached at 33 months and median disease-free survival (DFS) at 20 months: 14/22 patients are in continuous complete response with a median of 26 months. Patients who received lenalidomide alone were compared with patients who received lenalidomide in combination: OS and DFS did not differ. Progression-free survivals are significantly different: at 56 months, 36% in the combination group versus 13% in patients who received lenalidomide alone. Toxicities were manageable, even if 17 of them led to an early drug discontinuation., Conclusion: Lenalidomide therapy for relapsed MCL patients is effective and tolerable even in a real-life context., Implication for Practice: Several factors influence treatment choice in relapsed/refractory mantle cell lymphoma (rrMCL), and the therapeutic scenario is continuously evolving. In fact, rrMCL became the first lymphoma for which four novel agents have been approved: temsirolimus, lenalidomide, ibrutinib, and bortezomib. The rrMCL therapeutic algorithm is not so well established because data in the everyday clinical practice are still poor. Lenalidomide for rrMCL patients is effective and tolerable even in a real-life context., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

Chronic spontaneous urticaria (CSU) is a clinical condition characterized by spontaneous or inducible recurrent wheals. This condition may significantly affect quality of life of patients and of their families. Etiology is not identified in 25-85% of cases that are indicated as 'idiopathic', because all diagnostic tests are negative. Autoimmune processes may be present in 30-50% of patients, although a definite etiological diagnosis is seldom possible. Some patients, in fact, have autoantibodies against the high-affinity IgE receptor FcεR1 or IgE. These patients show an increased incidence of anti-thyroid autoantibodies and represent 30-50% of the patients designated as having CSU. Familial cold autoinflammatory syndrome (FCAS) must be distinguished from acquired cold urticaria, which is characterized by a rash occurring within a few minutes after cold exposure, and is often described as 'allergy to cold'. Cold urticaria (CU) is rare in childhood and is not linked to inflammatory markers. The treatment is based on antihistamines. However, in non-responders, a second-line treatment with omalizumab can show efficacy. We describe the clinical case of a 9-year-old-female with recurrent monthly episodes of fever, arthralgia, abdominal pain, and urticaria-angioedema who did not respond to steroids associated with antihistamines, however, showed the complete resolution of the disease with omalizumab.

In this manuscript for the first time we describe the concomitant diagnosis of primary renal non-Hodgkin lymphoma (PRL) and of a papillary urothelial cancer in a patient with megaloblastic anemia. PRL is a rare disease, since the kidney is one of the extranodal organs usually not containing lymphoid tissue. The disease usually affects adults with an average age of 60 years and slight male preponderance. Flank pain is the most common presenting symptom and different histologies have been reported. A review of literature indicated that simultaneous diagnosis of PRL and papillary urothelial carcinoma of the urether, makes our case unique. The early diagnosis of both diseases allowed the eradication of the two neoplasms by nephro-ureterecthomy and by performing subsequent systemic chemotherapy.

Antiphospholipid antibody syndrome (APS) is a disorder caused by circulating antibodies reacting with biological membranes and characterized by recurrent thrombosis, chronic thrombocytopenia and miscarriages. It has been reported to occur either as a primary syndrome or secondary to systemic autoimmune disorders. We describe a case of primary APS in a young patient, in whom the clinical course was particularly severe and complicated by a respiratory distress syndrome. The patient was resistant to a number of treatments, and eventually responded to intravenous high dose corticosteroids.