Tra essere e agire. I mille volti della paura nella trilogia di Batman di Christopher Nolan

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A MALDI-TOF MS approach for mammalian, human, and formula milks’ profiling

Human milk composition is dynamic, and substitute formulae are intended to mimic its protein content. The purpose of this study was to investigate the potentiality of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), followed by multivariate data analyses as a tool to analyze the peptide profiles of mammalian, human, and formula milks. Breast milk samples from women at different lactation stages (2 (n = 5), 30 (n = 6), 60 (n = 5), and 90 (n = 4) days postpartum), and milk from donkeys (n = 4), cows (n = 4), buffaloes (n = 7), goats (n = 4), ewes (n = 5), and camels (n = 2) were collected. Different brands (n = 4) of infant formulae were also analyzed. Protein content (<30 kDa) was analyzed by MS, and data were exported for statistical elaborations. The mass spectra for each milk closely clustered together, whereas different milk samples resulted in well-separated mass spectra. Human samples formed a cluster in which colostrum constituted a well-defined subcluster. None of the milk formulae correlated with animal or human milk, although they were specifically characterized and correlated well with each other. These findings propose MALDI-TOF MS milk profiling as an analytical tool to discriminate, in a blinded way, different milk types. As each formula has a distinct specificity, shifting a baby from one to another formula implies a specific proteomic exposure. These profiles may assist in milk proteomics for easiness of use and minimization of costs, suggesting that the MALDI-TOF MS pipelines may be useful for not only milk adulteration assessments but also for the characterization of banked milk specimens in pediatric clinical settings

In Vivo Confocal Imaging of the Conjunctiva as a Predictive Tool for the Glaucoma Filtration Surgery Outcome

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Gatekeeper Improves Voluntary Contractility in Patients With Fecal Incontinence

Background. Gatekeeper (GK) has shown to be safe and effective in patients with fecal incontinence (FI). We aimed to understand its mechanism of action by comparing pre- and post-implant change in the external anal sphincter (EAS) contractility. Methods. Study of EAS contractility was conducted in 16 FI females (median age = 69 years) before and after implant of 6 GK prostheses. Muscle tension (Tm), expressed in millinewtons per centimeter squared, mN(cm2) 121, was calculated using the equation Tm = P(ri)(tm) 121, where P is the average maximum squeeze pressure and ri and tm the inner radius and thickness of the EAS, respectively. The effect of a predefined set of covariates on Tm was tested by restricted maximum likelihood models. Results. Compared with baseline, despite unchanged tm (2.7 [2.5-2.8] vs 2.5 [2.2-2.8] mm; P =.31 mm), a significant increase in P (median = 45.8 [26.5-75.8] vs 60.4 [43.1-88.1] mm Hg; P =.017), and ri (12.4 [11.5-13.4] vs 18.7 [17.3-19.6] mm; P <.001) resulted in an increase in Tm (233.2 [123.8-303.2] vs 490.8 [286.9-562.4] mN(cm2) 121; P <.001) at 12 months after GK implant. Twelve-month follow-up improvements were also observed on Cleveland Clinic FI score (8-point median decrease; P =.0001), St Marks FI score (10-point median decrease; P <.0001), and American Medical Systems score (39-point median decrease; P <.0001). Restricted maximum likelihood models showed that years of onset of FI was negatively associated with change in Tm (P =.048). Conclusions. GK-related EAS compression positively influences muscle contractility by increasing ri, with consequent increase in Tm (length-tension relationship). Further studies are needed to confirm the long-term effectiveness of GK

A Novel Ex Vivo Approach Based on Proteomics and Biomarkers to Evaluate the Effects of Chrysene, MEHP, and PBDE-47 on Loggerhead Sea Turtles (Caretta caretta)

The principal aim of the present study was to develop and apply novel ex vivo tests as an alternative to cell cultures able to evaluate the possible effects of emerging and legacy contaminants in Caretta caretta. To this end, we performed ex vivo experiments on non-invasively collected whole-blood and skin-biopsy slices treated with chrysene, MEHP, or PBDE-47. Blood samples were tested by oxidative stress (TAS), immune system (respiratory burst, lysozyme, and complement system), and genotoxicity (ENA assay) biomarkers, and genotoxic and immune system effects were observed. Skin slices were analyzed by applying a 2D-PAGE/MS proteomic approach, and specific contaminant signatures were delineated on the skin proteomic profile. These reflect biochemical effects induced by each treatment and allowed to identify glutathione S-transferase P, peptidyl-prolyl cis-trans isomerase A, mimecan, and protein S100-A6 as potential biomarkers of the health-threatening impact the texted toxicants have on C. caretta. Obtained results confirm the suitability of the ex vivo system and indicate the potential risk the loggerhead sea turtle is undergoing in the natural environment. In conclusion, this work proved the relevance that the applied ex vivo models may have in testing the toxicity of other compounds and mixtures and in biomarker discovery

Budget impact of bi-monthly use of Cetuximab in patients diagnosed with mCRC

Aim: Cetuximab is used for the treatment of RAS wild-type metastatic colorectal cancer patients. Standard administration schedule is once a week; however, the bioequivalence of an every-other-week (EOW) schedule was demonstrated. Methods: We compared a base case scenario of 100% weekly administration to an EOW at 50 or 100%. Medical examinations, patient management and loss of productivity were considered. Results: Base case was estimated at €100.6 million versus €92.8 million and €84.9 million of EOW 50 and 100%, which showed a cost reduction of 8 and 16%, respectively. Indirect costs accounted for 65% in both scenarios. Conclusion: The adoption of an EOW administration schedule of cetuximab reduced direct and indirect costs substantially

Allergic adverse events following immunization: Data from post-marketing surveillance in Apulia region (South of Italy)

IntroductionAmong adverse events following immunization (AEFIs), allergic reactions elicit the most concern, as they are often unpredictable and can be life-threatening. Their estimates range from one in 1,000,000 to one in 50,000 vaccine doses. This report describes allergic events following immunization reported from 2020 to 2021 in Puglia, a region in the South-East of Italy with around 4 million inhabitants. Its main objective is to describe the allergic safety profile of currently employed vaccines.Materials and methodsThis is a retrospective observational study. The study period spanned from January 2020 to December 2021, and the whole Apulian population was included in the study. Information regarding AEFIs reported in Puglia during the study period was gathered from the Italian Drug Authority’s pharmacovigilance database (National Pharmacovigilance Network, RNF). The overall number of vaccine doses administered was extrapolated by the Apulian online immunization database (GIAVA). Reporting rates were calculated as AEFIs reported during a certain time span/number of vaccine doses administered during the same period.Results10,834,913 vaccine doses were administered during the study period and 95 reports of allergic AEFIs were submitted to the RNF (reporting rate 0.88/100,000 doses). 27.4% of the reported events (26/95) were classified as serious (reporting rate 0.24/100,000 doses). 68 out of 95 (71.6%) adverse events were at least partially resolved by the time of reporting and none of them resulted in the subject’s death.ConclusionsAllergic reactions following vaccination were rare events, thus confirming the favourable risks/benefits ratio for currently marketed vaccines

Positive Energy Districts: Fundamentals, Assessment Methodologies, Modeling and Research Gaps

The definition, characterization and implementation of Positive Energy Districts is crucial in the path towards urban decarbonization and energy transition. However, several issues still must be addressed: the need for a clear and comprehensive definition, and the settlement of a consistent design approach for Positive Energy Districts. As emerged throughout the workshop held during the fourth edition of Smart and Sustainable Planning for Cities and Regions Conference (SSPCR 2022) in Bolzano (Italy), further critical points are also linked to the planning, modeling and assessment steps, besides sustainability aspects and stakeholders' involvement. The "World Caf & eacute;" methodology adopted during the workshop allowed for simple-but also effective and flexible-group discussions focused on the detection of key PED characteristics, such as morphologic, socio-economic, demographic, technological, quality-of-life and feasibility factors. Four main work groups were defined in order to allow them to share, compare and discuss around five main PED-related topics: energy efficiency, energy flexibility, e-mobility, soft mobility, and low-carbon generation. Indeed, to properly deal with PED challenges and crucial aspects, it is necessary to combine and balance these technologies with enabler factors like financing instruments, social innovation and involvement, innovative governance and far-sighted policies. This paper proposes, in a structured form, the main outcomes of the co-creation approach developed during the workshop. The importance of implementing a holistic approach was highlighted: it requires a systematic and consistent integration of economic, environmental and social aspects directly connected to an interdisciplinary cross-sectorial collaboration between researchers, policymakers, industries, municipalities, and citizens. Furthermore, it was reaffirmed that, to make informed and reasoned decisions throughout an effective PED design and planning process, social, ecological, and cultural factors (besides merely technical aspects) play a crucial role. Thanks to the valuable insights and recommendations gathered from the workshop participants, a conscious awareness of key issues in PED design and implementation emerged, and the fundamental role of stakeholders in the PED development path was confirmed

Gut Microbiota, Metabolome, and Body Composition Signatures of Response to Therapy in Patients with Advanced Melanoma

Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid to the gut microbiota and other modifiable patient factors (e.g., diet and body composition), though their role in influencing therapeutic responses has yet to be defined. Here, we characterized a cohort of 31 patients with unresectable IIIC-IV-stage cutaneous melanoma prior to initiation of targeted or first-line immunotherapy via the following methods: (i) fecal microbiome and metabolome via 16S rRNA amplicon sequencing and gas chromatography/mass spectrometry, respectively, and (ii) anthropometry, body composition, nutritional status, physical activity, biochemical parameters, and immunoprofiling. According to our data, patients subsequently classified as responders were obese (i.e., with high body mass index and high levels of total, visceral, subcutaneous, and intramuscular adipose tissue), non-sarcopenic, and enriched in certain fecal taxa (e.g., Phascolarctobacterium) and metabolites (e.g., anethole), which were potentially endowed with immunostimulatory and oncoprotective activities. On the other hand, non-response was associated with increased proportions of Streptococcus, Actinomyces, Veillonella, Dorea, Fusobacterium, higher neutrophil levels (and a higher neutrophil-to-lymphocyte ratio), and higher fecal levels of butyric acid and its esters, which also correlated with decreased survival. This exploratory study provides an integrated list of potential early prognostic biomarkers that could improve the clinical management of patients with advanced melanoma, in particular by guiding the design of adjuvant therapeutic strategies to improve treatment response and support long-term health improvement

Yeast-derived recombinant avenanthramides inhibit proliferation, migration and epithelial mesenchymal transition of colon cancer cells

Avenanthramides (Avns), polyphenols found exclusively in oats, are emerging as promising therapeutic candidates for the treatment of several human diseases, including colon cancer. By engineering a Saccharomyces cerevisiae strain, we previously produced two novel phenolic compounds, N-(E)-p-coumaroyl-3-hydroxyanthranilic acid (Yeast avenanthramide I, YAvnI) and N-(E)-caffeoyl-3-hydroxyanthranilic acid (Yeast avenanthramide II, YAvnII), which are endowed with a structural similarity to bioactive oat avenanthramides and stronger antioxidant properties. In this study, we evaluated the ability of these yeast-derived recombinant avenanthramides to inhibit major hallmarks of colon cancer cells, including sustained proliferation, migration and epithelial-mesenchymal transition (EMT). Using the human colon adenocarcinoma cell line HT29, we compared the impact of YAvns and natural Avns, including Avn-A and Avn-C, on colon cancer cells by performing MTT, clonogenic, adhesion, migration, and anchorage-independent growth assays, and analyzing the expression of EMT markers. We found that both YAvns and Avns were able to inhibit colon cancer cell growth by increasing the expression of p21, p27 and p53 proteins. However, YAvns resulted more effective than natural compounds in inhibiting cancer cell migration and reverting major molecular features of the EMT process, including the down-regulation of E-cadherin mRNA and protein levels