University of Udine
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Beyond Hormone Receptors: liquid biopsy tools to unveil new clinical meanings and empower therapeutic decision-making in Luminal-like metastatic breast cancer
Get PDFImmunohistochemical (IHC) tissue profiling is a standard practice in the management of metastatic breast cancer (mBC), that enables the identification of distinct biological phenotypes based on hormone receptors' expression. Luminal-like tumors primarily benefit from a first line treatment strategy combining endocrine therapy and cyclin-dependent kinase 4/6 inhibitors. However, IHC analyses necessitate invasive procedures and may encounter technical and interpretational challenges. In the current era of precision medicine, liquid biopsy holds potential to provide clinicians with additional insights into disease biology, including mechanisms underlying endocrine resistance and disease progression. Several liquid-based biomarkers are entering clinical practice and hold prognostic and predictive values in Luminal-like mBC, while many others are currently being investigated. The present work aims to summarize the current evidence regarding the clinical meanings of hormone receptors and their downstream molecular pathways, alongside their implications for therapeutic decision-making in Luminal-like mBC
Synergistic Dual Ag/Cu Ion Implantation to Enhance Antimicrobial Defense on Boston Keratoprosthesis
Get PDFThe Boston keratoprosthesis (BKPro) is a critical device for vision restoration in complex cases of corneal blindness, although its long-term retention is challenged by infection risks. This study aims to enhance the antimicrobial properties of the titanium (Ti) backplate of the BKPro by ion implanting silver and copper ions to achieve effective infection control while maintaining cytocompatibility. Research on antimicrobial modifications for BKPro is limited, and while metallic ions like Ag and Cu show promise for biomaterial improvement, their effects on human corneal keratocytes (HCKs) require further study. Ag and Cu were implanted onto rough Ti surfaces, as mono- and coimplantations. Cytotoxicity was assessed in HCKs, and antimicrobial efficacy was tested against Pseudomonas aeruginosa and Candida albicans. After 21 d, monoimplanted Ag samples released 300.4 ppb of Ag+, coimplanted samples released 427.5 ppb of Ag+ and 272.3 ppb of Cu ions, and monoimplanted Cu samples released 567.0 ppb of Cu ions. All ion-implanted surfaces supported HCK proliferation, exhibited no cytotoxicity, and showed strong antimicrobial activity. Ag-implanted surfaces provided antibacterial effects through membrane disruption and reactive oxygen species generation, while Cu-implanted surfaces exhibited antifungal effects via impaired enzymatic functions and reactive oxygen species. Coimplanted AgCu surfaces demonstrated synergistic antimicrobial effects, resulting from the synergy between the bactericidal actions of Ag and the oxidative stress contributions of Cu. Additionally, ion-implanted surfaces enhanced HCK adhesion under co-culture conditions. In conclusion, ion implantation effectively imparts antimicrobial properties to the Ti backplate of BKPro, reducing infection risks while preserving compatibility with corneal cells
BEETter AGING: Short-Term Dietary Nitrate Supplementation Enhances Muscle Contractile Properties in Older But Not in Young Adults
No full textPurpose: Dietary nitrate (NO3-) supplementation has been shown to improve skeletal muscle contractile function and reduce fatigue, potentially due to alterations in skeletal muscle Ca2+ handling/sensitivity. Since aging muscle can have impaired Ca2+ handling, the aim of the study was to evaluate the effects of dietary NO3- supplementation on muscle contractile properties in young and older adults. Methods: Eleven older (69±4yrs, O) and 11 young (26±2yrs, YG) adults consumed either NO3-rich beetroot juice (BR) or placebo (PLA), for 7 days. After supplementations, plantar flexors of dominant leg were evaluated as follow: a) maximal voluntary isometric contraction (MVIC); b) potentiated single twitches (Twpot) and double twitches electrical stimulations at the frequency of 100Hz (Db100) on the tibial posterior nerve; c) a fatigue isometric (70% of MVIC) test until exhaustion. The force-frequency relationship was assessed with trains of electrical pulses across a wide range of frequencies on the muscle belly of the non-dominant leg. Results: BR supplementation increased plasma [NO3-] and nitrite [NO2-] in both O and YG compared to PLA (more than 7-fold; all P≤0.02). No changes were observed in MVC, Twpot, and Db100 force after BR compared to PLA in both YG and O. Only in O, Db100 area under the curve (-7±6 N∙s change from PLA) and half relaxation time (-0.05±0.06s change from PLA) were significantly reduced. and time to exhaustion (+32±43s change from PLA) was significantly longer (all P<0.02) after BR. In O, BR also significantly increased submaximal force produced by trains of electrical pulses (P < 0.001). Conclusions: NO3- supplementation positively affects muscle contractile proprieties, submaximal electrically evoked force production and fatigue resistance in older adults while these positive results were not found in young
Critique of Forest Intelligence: Scenarios for Architecture and the City in the Twenty-First Century (and Beyond)
Get PDFThis contribution starts from a question: in what terms can the "design reason" that is guiding the action of numerous contemporary architects, city planners and project makers be considered and defined? We argue that that such reason can be defined as "forest intelligence", opposed to the "human-animal intelligence" that has instead characterised the repertoire of architectural-urban solutions from modernity onwards. The latter is characterised by verticality, exemplified by classes of opposites such as centre and periphery, the space of "nature" and the space of the "city". On the other hand, the new "forest intelligence" is characterised by horizontality – urban polycentrism, interrelation between the parts of the city, absence of a clear division between "natural" and "urban" space. Therefore, we have investigated three remarkable moments of the first quarter of our century. From the art world, the Documenta 13 exhibition (2012); representing architecture and landscape design, Gilles Clément’s "Manifeste du Tiers paysage"
(2004); and from the field of politics, the "New Landscape Declaration" (2016), an updated manifesto for landscape practice. We believe that these three specific and topical events can be understood as activators, initiators and at the same time as spaces for publicising the aforementioned "forest intelligence"
Alectinib for the treatment of papillary thyroid carcinoma harbouring STRN – ALK fusion
No full textBackground: Anaplastic Lymphoma Kinase (ALK) rearrangement is a rare alteration in differentiated thyroid carcinomas (DTCs). Due to its low prevalence, a few evidence are available about the use of ALK inhibitors in advanced DTCs. Methods: We report the case of a striatin (STRN) - ALK translocated advanced thyroid carcinoma. STRN – ALK translocation was detected by NGS – RNA analysis. Results: A 74-year-old woman received first line alectinib for the treatment of a STRN - ALK translocated advanced thyroid carcinoma with symptomatic bilateral lung localizations. The dose of alectinib was progressively reduced due to the toxicity, but the treatment is still ongoing after 17 months with complete radiological response and clinical benefit. Conclusion: Here we report the first case in Europe of STRN - ALK translocated advanced thyroid carcinoma successfully treated with alectinib
New oxygen carriers for efficient syngas and H2 production by chemical looping steam methane reforming
Get PDFThe research work illustrate the development of catalyst-promoted Fe-based Oxygen Carriers (OC) for the Chemical Looping Steam Reforming (CL-SMR) process. Goal of the study was to explore novel methods for preparing oxygen carrier materials that combine the advantages of Fe-containing oxides, including environmental compatibility, relatively low cost, and the ability to be partially or fully reoxidized by steam, with the high CH4 activation ability of Ni. The process enables the simultaneous production of pure hydrogen, along with the syngas derived from the partial oxidation of the hydrocarbons feed. The work provides guidance for the design of physically mixed OC-supported catalyst composite carrier systems, through the investigation of the CL-SMR performances, chemical compatibility, stability, and composition of such systems. Furthermore, a preliminary investigation into the use of an exsolving Ni-doped Fe-based perovskite highlights the potential of this class of materials in chemical looping processes—a potential that has remained largely unexplored until recently
Temperament and Character Moderate the Effects of Mindfulness Training on Psychological and Professional Well-Being of School Teachers
Get PDFObjectives: The study aimed to investigate the pre-to-post effects of mindfulness training on school teachers’ psychological and professional well-being, as well as to explore the moderating role of temperament and character on these effects. Method: An 8-week mindfulness-based intervention was delivered via internet-based group meetings to Italian teachers (n = 139), who were assessed within two weeks before and after the intervention with self-report measures of emotional distress (Hospital Anxiety and Depression Scale), interoceptive awareness (Multidimensional Assessment of Interoceptive Awareness), and professional efficacy (Teachers’ Sense of Efficacy Scale), as well as with the Temperament and Character Inventory. A control group of teachers (n = 47) was tested with the same measures in two temporally-matched sessions. Results: Analysis of variance showed positive intervention effects on anxiety (medium effect size), on six of the eight dimensions of interoceptive awareness (medium-to-large effect size) and on two of the three scales of professional efficacy (small-to-medium effect size). Moderation analysis identified the following effects of temperament and character on outcomes: (1) reduced anxiety only for higher baseline reward dependence, or lower-to-middle baseline self-directedness; (2) improved interoceptive attention regulation specifically for middle-to-higher baseline persistence; (3) improved teacher efficacy for student engagement only for lower baseline self-transcendence. Conclusions: The study shows the positive effects of mindfulness training on teachers' psychological and professional well-being. It also highlights the importance of considering the impact of temperament and character dimensions on these effects, for example for developing effective mindfulness-based interventions for teachers. Future research should explore potential mechanisms of action underlying the observed effects and evaluate them in the long term. Preregistration: This study is not preregistered
Alcohol and forensic pathology. Systematic reviews of literature, analysis of casuistries and of bizarre fatal cases in Friuli
Get PDFIn forensic practice, ethanol is by far the most detected drug in toxicological laboratories and the determination of its blood concentration (BAC) has important criminal and civil implications. However, postmortem BAC interpretation may be problematic, because of possible changes due to post-mortem artifacts.
A method to differentiate the source of ethanol in post-mortem blood samples is the analysis of alcohols levels in alternative-to-blood specimens (e.g. vitreous humour or urine).
Two different research lines were the object of this thesis: 1) to perform a retrospective analysis of necroscopic records of four specific types of deaths occurred in Friuli throughout the period 1993-2020: homicide-suicides (10 perpetrators and 13 victims), complex suicides (n=24), fire- (n=39) and water-related-deaths (n=69). The role of ethanol in these specific contexts was investigated through a review of the literature and unusual cases were separately discussed; 2) to analyse the relationship between alcohol levels detected in the synovial fluid and those detected in blood and in urine, in order to evaluate the potential role of this biological fluid as an alternative-to-blood specimen in post-mortem ethanol interpretation.
Alcohol was the most detected drug in our case series and in literature: it resulted to have a neglegible influence on perpetrators of homicide-suicides (2/6 assailants with BACs of 0.21 and 0.25 g/L) and a significant role in the other types of death (BACs>0.5 g/L were detected in 3/6 victims of homicide-suicides, 5/20 fire-deaths and 6/11 complex suicides and a state of acute ethanol intoxication was noted in 22/40 water-related deaths).
Literature review showed that medico-legal aspects of alcohol have been investigated in many studies, but little research has been done on some peculiar issues such as post-mortem alcohol interpretation in burned and submerged bodies, with a need, therefore, to improve the current state of knowledge of these topics.
Weak agreements were observed between alcohol concentration of blood and synovial fluid (r=0.60, n=16) and urine and synovial alcohol (r=0.78, n=10).
When it was possible to differentiate individuals in relationship to the stage of alcohol metabolism in which the death occurred, a strong agreement was observed in individual deceased during the post-absorption phase (both blood/synovial fluid and urine/synovial fluid: r=0.99, n=5) and a weak agreement in individuals deceased during the absorption phase (blood/synovial fluid: r=0.56 and urine/synovial fluid: r=0.61, both n=4). However, the research was carried out on a small sample and it is necessary to corroborate these preliminary results
Unravelling the intricate language of fish guts: Impact of plant-based vs. plant-insect-poultry-based diets on intestinal pathways in European seabass
Get PDFThe long-term sustainability of aquaculture depends on finding economically viable and environmentally friendly feed ingredients to reduce the use of fishmeal and fish oil. An optimal strategy for the industry is not to identify substitutes or alternatives, but to find a combination of complementary raw materials that together meet the specific nutritional requirements for a given farmed fish species. The study aimed to examine the effects of different diets on the pyloric caeca and distal intestine of subadult European seabass (Dicentrarchus labrax) by applying transcriptomics and transmission electron microscopy. The study examined three dietary approaches: the classic fishmeal-based diet, a plant-based diet, and a plant-insect-poultry-based diet. The distal intestine was more sensitive to dietary changes than the pyloric caeca. The differentially expressed genes in both experimental diets were mainly involved in the digestion and absorption of proteins, fats, and vitamins. The overall transcriptomic changes were greater in the plant-based group than in the plant-insect-poultry-based group and included a greater number of overrepresented metabolic and signalling pathways. In contrast to the transcriptomic results, the ultrastructural findings showed decreased inflammation and/or evidence of tissue repair in the plant-based group, particularly in the pyloric caeca. Since the nutritional quality of all fish groups in this study was previously evaluated positively, the detected transcriptome-level changes can serve as evidence supporting the efficient nutrient utilisation and adaptability in European seabass. The study provides valuable insight into the potential benefits and implications of these dietary modifications on intestinal health and pathway regulation in European seabass. This can serve as a basis for further development of sustainable European seabass aquaculture practices and optimisation of diet formulations