INVESTIGATION OF THE UNDERGROUND BUILDING HERITAGE AND THE MECHANISM OF WATER FLOWING IN QANĀTS IN PALERMO THROUGH INNOVATIVE SURVEYING TECHNIQUES

The valorisation, protection and preservation policies for the underground building heritage are often difficult to implement due to an inadequate knowledge of hypogeal constructions. The complex and widespread underground structures of the vast “Cavo” Heritage (“horizontal wells”, “shelf wells” or “well tunnels”), so called qanāts, hidden underground and built over the centuries in Palermo, representing an evocative testimony to the history of water culture in the ancient city. Through the historical and constructive analyses and the implementation and development of measurement and 3D representation and visualization, first actions have been carried out. The paper will present the first results of the restoration project and the path of re-introduction in the fruition network of the qanāt “Gesuitico alto”, developed also in the field of “iHeritage. Mediterranean Platform for UNESCO Cultural Heritage” project, financed by ENI CBC MED Programme 2014-2020. The paper presents an experimentation of a procedural workflow of data acquisition, analysis and subsequent 3D virtual navigation of hypogeal environments. The methodology used is the SLAM with a last generation WMLS. The platform of virtual reality visualization, within UnReal Engine, allows the user to immerse and navigate in the anthropic environment by engaging it with a set of infographics that highlight the virtual visit

Confirmation of increased and more severe adolescent mental health-related in-patient admissions in the COVID-19 pandemic aftermath: A 2-year follow-up study

: COVID-19 pandemic may have affected youth's mental wellbeing. Youth admissions for mental health emergencies over the 2-year period following the COVID-19 outbreak (March 2020-February 2022) were compared to those occurring in the same period of 2018-2020, with reference to individual and clinical data. The study identified 30 admissions in the pre-pandemic period and 65 (+116.7%) in the post-pandemic period, with the latter being younger, less likely to have a personal psychiatric history, and more likely to receive psychopharmacological treatment. A higher likelihood of earlier, ex novo psychiatric manifestations, requiring medication to reach clinical stability, in the post-COVID era, is suggested

A multi-state analysis of disease trajectories and mental health transitions in patients with type 2 diabetes: A population-based retrospective cohort study utilizing health administrative data

Aims: To investigate the risk of major depression and dementia in patients with type 2 diabetes, including dementia resulting from depression, and their impact on diabetes-related complications and mortality. Methods: We conducted a population-based retrospective cohort study including 11,441 incident cases of diabetes in 2015-2017, with follow-up until 2022. A multi-state survival analysis was performed on a seven-state model with 15 transitions to capture disease progression and onset of mental disorders. Results: Eight-year probabilities of depression, dementia, diabetes-related complications, and death were 9.7% (95% CI 8.7-10.7), 0.9% (95% CI 0.5-1.3), 10.4% (95% CI 9.5-11.4), and 14.8% (95% CI 13.9-15.7), respectively. Depression increased the risk of dementia up to 3.7% (95% CI 2.0-5.4), and up to 10.3% (95% CI 0.3-20.4) if coupled with diabetes complications. Eight-year mortality was 37.5% (95% CI 33.1-42.0) after depression, 74.1% (95% CI 63.7-84.5) after depression plus complications, 76.4% (95% CI 68.8-83.9) after dementia, and 98.6% (95% CI 96.1-100.0) after dementia plus complications. Conclusions: The interconnections observed across depression, dementia, complications, and mortality underscore the necessity for comprehensive and integrated approaches in managing diabetes. Early screening for depression, followed by timely and targeted interventions, may mitigate the risk of dementia and improve diabetes prognosis

[Cost-Utility Analysis of Dupilumab for the Treatment of Severe Atopic Dermatitis in Children and Adolescents in Italy]

BACKGROUND AND OBJECTIVE: Atopic dermatitis (AD) is a chronic, multifactorial, inflammatory condition characterized by a significant impact on patients' quality of life. Dupilumab is reimbursed by the Italian Medicines Agency (AIFA) for the treatment of adolescent and adult patients with severe AD (according to AIFA registry criteria). Recently, dupilumab has been reimbursed in the treatment of children with severe AD. The objective of this analysis was to estimate the incremental cost-utility ratio (ICUR) of dupilumab compared to current supportive care (SC), for the treatment of severe AD in children (6-11 years) and adolescents (12-17 years) in Italy.MATERIALS AND METHODS: Cost-effectiveness analysis was conducted using a 1-year decision tree followed by a Markov model over a lifetime period. The base case analysis was performed on the overall population of the LIBERTY AD ADOL (NCT03054428) and LIBERTY AD PEDS (NCT03345914) studies, adopting the National Health Service (NHS) perspective. The following costs were considered: acquisition of treatment, management of disease, adverse events and complications. The robustness of the model was tested through sensitivity analysis. In addition, a scenario analysis adopting the social perspective was performed.RESULTS: In the base case, over a lifetime, dupilumab was more effective than SC in both children and adolescents (+2.44 and +1.62 quality-adjusted life years—QALYs, respectively). The introduction of dupilumab generated an increase in treatment costs (+€ 64,800 and +€ 52,853 € for children and adolescents, respectively), partially offset by a decrease in the costs of disease management and complications. Incremental cost-utility ratios (ICURs) were € 21,189 per QALY gained, for children, and € 26,569 per QALY gained, for adolescents. In both cases, the ICUR was lower than the willingness to pay threshold considered in Italy (€ 50,000 per QALY gained). Both the deterministic and probabilistic sensitivity analysis confirmed the robustness of the base case results. Finally, the scenario analysis, adopting the social perspective, showed coherent results compared to the base case.DISCUSSION: Dupilumab is a cost-effective option for the treatment of children and adolescents with severe AD eligible for systemic treatment in Italy compared to SC, from both the NHS and social perspective, confirming the results obtained in the adult population

Case report: The CCDC103 variant causes ultrastructural sperm axonemal defects and total sperm immotility in a professional athlete without primary ciliary diskinesia

Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder characterized by abnormal ciliary motion, due to a defect in ciliary structure and/or function. This genetic condition leads to recurrent upper and lower respiratory infections, bronchiectasis, laterality defect, and subfertility. Male infertility is often associated with PCD, since the ultrastructure of the axoneme in the sperm tail is similar to that of the motile cilia of respiratory cells. We present the first reported case of a male patient from a non-consanguineous Italian family who exhibited a severe form of asthenozoospermia factor infertility but no situs inversus and absolutely no signs of the clinical respiratory phenotype, the proband being a professional basketball player. Whole-exome sequencing (WES) has identified a homozygote mutation (CCDC103 c.461 A > C, p.His154Pro) in the proband, while his brother was a heterozygous carrier for this mutation. Morphological and ultrastructural analyses of the axoneme in the sperm flagellum demonstrated the complete loss of both the inner and outer dynein arms (IDA and ODA, respectively). Moreover, immunofluorescence of DNAH1, which is used to check the assembly of IDA, and DNAH5, which labels ODA, demonstrated that these complexes are absent along the full length of the flagella in the spermatozoa from the proband, which was consistent with the IDA and ODA defects observed. Noteworthy, TEM analysis of the axoneme from respiratory cilia showed that dynein arms, although either IDAs and/or ODAs seldom missing on some doublets, are still partly present in each observed section. This case reports the total sperm immotility associated with the CCDC103 p.His154Pro mutation in a man with a normal respiratory phenotype and enriches the variant spectrum of ccdc103 variants and the associated clinical phenotypes in PCD, thus improving counseling of patients about their fertility and possible targeted treatments

Preventing the acute skin side effects in patients treated with radiotherapy for breast cancer: the use of corneometry in order to evaluate the protective effect of moisturizing creams

BACKGROUND AND PURPOSE: The purpose of this study was to add, to the objective evaluation, an instrumental assessment of the skin damage induced by radiation therapy. MATERIALS AND METHODS: A group of 100 patients affected by breast cancer was recruited in the study over one year. Patients were divided into five groups of 20 patients. For each group it was prescribed a different topical treatment. The following products were used: Betaglucan, sodium hyaluronate (Neoviderm®), Vitis vinifera A. s-I-M.t-O.dij (Ixoderm®), Alga Atlantica plus Ethylbisiminomethylguaicolo and Manganese Cloruro (Radioskin1®) and Metal Esculetina plus Ginko Biloba and Aloe vera (Radioskin 2®); Natural triglycerides-fitosterols (Xderit®); Selectiose plus thermal water of Avene (Trixera+®). All hydrating creams were applied twice a day starting 15 days before and one month after treatment with radiations. Before and during treatment patients underwent weekly skin assessments and corneometry to evaluate the symptoms related to skin toxicity and state of hydration. Evaluation of acute cutaneous toxicity was defined according to the RTOG scale. RESULTS: All patients completed radiotherapy; 72% of patients presented a G1 cutaneous toxicity, 18% developed a G2 cutaneous toxicity, 10% developed a G3 toxicity, no one presented G4 toxicity. The corneometry study confirmed the protective role of effective creams used in radiation therapy of breast cancer and showed its usefulness to identify radiation-induced dermatitis in a very early stage. CONCLUSIONS: The preventive use of topic products reduces the incidence of skin side effects in patients treated with radiotherapy for breast cancer. An instrumental evaluation of skin hydration can help the radiation oncologist to use strategies that prevent the onset of toxicity of high degree. All moisturizing creams used in this study were equally valid in the treatment of skin damage induced by radiotherapy

Correlation between the Antimicrobial Activity and Metabolic Profiles of Cell Free Supernatants and Membrane Vesicles Produced by Lactobacillus reuteri DSM 17938

The aim of the work is to assess the antimicrobial activities of Cell Free Supernatants (CFS) and Membrane Vesicles (MVs), produced by Lactobacillus reuteri DSM 17938, versus Gram-positive and Gram-negative bacteria and investigate their metabolic profiles. The Minimum Inhibitory Concentration was determined through the broth microdilution method and cell proliferation assay while the Minimum Bactericidal Concentration was determined by Colony Forming Units counts. The characteristics of the antimicrobial compounds were evaluated by pH adjustments, proteinase treatment, and size fractionation of the CFS. The cytotoxicity of CFS was tested on two human cell lines. A detailed snapshot of the L. reuteri metabolism was attained through an untargeted metabolic profiling by means of high resolution Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) coupled with Electrospray Ionization Source (ESI). The results showed (i) a greater efficacy of CFS and its fractions towards Gram-negative compared to Gram-positive bacteria; (ii) an antimicrobial effect related to pH-dependent compounds but not to MVs; (iii) a molecular weight < 3 KDa as well as an a non-proteinaceous nature of the antimicrobial compounds; and (iv) more than 200 and 500 putative metabolites annotated in MVs and supernatants, covering several classes of metabolites, including amino acids, lipids, fatty and organic acids, polyalcohols, nucleotides, and vitamins. Some putative compounds were proposed not only as characteristic of specific fractions, but also possibly involved in antimicrobial activity

Mesenchymal stem cell-based tissue engineering strategy for cartilage regeneration: A morphomolecular study

Articular cartilage is an avascular and aneural tissue with poor self-repair capacity. Pathological conditions leading to the cartilage degeneration, such as osteoarthritis (OA), have prompted the development of strategies aimed to its regeneration, such as mesenchymal stem cells (MSCs)-based tissue engineering approach. The aim of this study was to investigate if chondrocytes, differentiated from rat adipose tissue derived-MSCs (AMSCs) and seeded on Collagen Cell Carrier (CCC) scaffolds, are able to constitute a morphologically and biochemically healthy hyaline cartilage. To this purpose the AMSCs were primarily differentiated in chondrocytes through chondrogenic medium and subsequently cultured for 6 weeks on CCC scaffolds. The expression of osteoblast (Runt-related transcription factor 2 (RUNX2) and osteocalcin), chondrocyte (collagen I, II and lubricin) and apoptosis (caspase-3) biomarkers were evaluated in undifferentiated AMSCs, AMSCs-derived chondrocytes cultured in monolayer and AMSCs-derived chondrocytes seeded on CCC scaffolds, by different techniques such as immunohistochemistry, ELISA, Western blot and gene expression analyses. AMSCs-derived chondrocytes cultured on CCC scaffolds showed the increased expression of collagen II and lubricin, whereas the expression of collagen I, RUNX2, osteocalcin and caspase-3 resulted decreased when compared to the other groups. In conclusion, the results of this study suggest a possible role of AMSCs and the use of CCC scaffolds for therapeutic strategies aimed to the articular cartilage regeneration

In-hospital percentage BNP reduction is highly predictive for adverse events in patients admitted for acute heart failure: the Italian RED Study

Introduction: Our aim was to evaluate the role of B-type natriuretic peptide (BNP) percentage variations at 24 hours and at discharge compared to its value at admission in order to demonstrate its predictive value for outcomes in patients with acute decompensated heart failure (ADHF). Methods: This was a multicenter Italian (8 centers) observational study (Italian Research Emergency Department: RED). 287 patients with ADHF were studied through physical exams, lab tests, chest X Ray, electrocardiograms (ECGs) and BNP measurements, performed at admission, at 24 hours, and at discharge. Follow up was performed 180 days after hospital discharge. Logistic regression analysis was used to estimate odds ratios (OR) for the various subgroups created. For all comparisons, a P value 46% at discharge had an area under curve (AUC) of 0.70 (P 300 pg/mL. A BNP reduction of 25.9% after 24 hours had an AUC at ROC curve of 0.64 for predicting adverse events (P 46% was 4.775 (95% confidence interval (CI) 1.76 - 12.83, P 300 pg/mL and whose percentage decrease at discharge was 46% was 9.614 (CI 4.51 - 20.47, P 46% at hospital discharge compared to the admission levels coupled with a BNP absolute value < 300 pg/mL seems to be a very powerful negative prognostic value for future cardiovascular outcomes in patients hospitalized with ADHF