On the need of a scale-dependent material characterization to describe the mechanical behavior of 3D printed Ti6Al4V custom prostheses using finite element models

Additive manufacturing is widely used in the orthopaedic industry for the high freedom and flexibility in the design and production of personalized custom implants made of Ti6Al4V. Within this context, finite element modeling of 3D printed prostheses is a robust tool both to guide the design phase and to support clinical eval-uations, possibly virtually describing the in-vivo behavior of the implant. Given realistic scenarios, a suitable description of the overall implant's mechanical behavior is unavoidable. Considering typical custom prostheses' designs (i.e. acetabular and hemipelvis implants), complex designs involving solid and/or trabeculated parts, and material distribution at different scales hinder a high-fidelity modeling of the prostheses.Moreover, uncertainties in the production and in the material characterization of small parts approaching the accuracy limit of the additive manufacturing technology still exist.While recent works suggest that the mechanical properties of thin 3D-printed parts may be peculiarly affected by specific processing parameters (i.e. powder grain size, printing orientation, samples' thickness) as compared to conventional Ti6Al4V alloy, the current numerical models make gross simplifications in describing the complex material behavior of each part at different scales.The present study focuses on two patient-specific acetabular and hemipelvis prostheses, with the aim of experimentally characterizing and numerically describing the dependency of the mechanical behavior of 3D printed parts on their peculiar scale, therefore, overcoming one major limitation of current numerical models. Coupling experimental activities with finite element analyses, the authors initially characterized 3D printed Ti6Al4V dog-bone samples at different scales, representative of the main material components of the investigated prostheses. Afterwards, the authors implemented the characterized material behaviors into finite element models to compare the implications of adopting scale-dependent vs. conventional scaleindependent approaches in predicting the experimental mechanical behavior of the prostheses in terms of their overall stiffness and the local strain distribution. The material characterization results highlighted the need for a scale-dependent reduction of the elastic modulus for thin samples compared to the conventional Ti6Al4V, which is fundamental to properly describe the overall stiffness and local strain distribution on the prostheses.The presented works demonstrate how an appropriate material characterization and a scale-dependent ma-terial description is needed to develop reliable FE models of 3D printed implants characterized by a complex material distribution at different scales

Post-Irradiation Hyperamylasemia Is a Prognostic Marker for Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in Pediatric Population: A Retrospective Single-Centre Cohort Analysis

Background: Total body irradiation (TBI) is a mandatory step for patients with acute lymphoblastic leukemia (ALL), undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In the past, amylases have been reported to be a possible sign of TBI toxicity. We investigated the relationship between total amylases (TA) and transplant-related outcomes in pediatric recipients. Methods: We retrospectively analyzed the medical records of all the patients who underwent allogeneic HSCT between January 2000 and November 2019. The inclusion criteria were the following: recipient's age between 2 and 18, diagnosis of ALL, no previous transplantation, and use of TBI-based conditioning. The serum total amylase and pancreatic amylase were evaluated before, during, and after transplantation. Cytokines and chemokines assays were retrospectively performed. Results: 78 patients fulfilled the inclusion criteria. Fifty-seven patients were treated with fractionated TBI, and 21 with a single-dose regimen. The overall survival (OS) was 62.8%. Elevated values of TA were detected in 71 patients (91%). The TA were excellent in predicting the OS (AUC = 0.773; 95% CI = 0.66-0.86; p < 0.001). TA values below 374 U/L were correlated with a higher OS. The highest mean TA values (673 U/L) were associated with a high disease-progression mortality rate. The TA showed a high predictive performance for disease progression-related death (AUC = 0.865; 95% CI = 0.77-0.93; p < 0.0001). Elevated TA values were also connected with significantly higher levels of proinflammatory cytokines, such as TNF-alpha, IL-6, and RANTES (p < 0.001). Conclusions: this study shows that TA is a valuable predictor of post-transplant OS and increased risk of leukemia relapse

In vitro downregulated hypoxia transcriptome is associated with poor prognosis in breast cancer

© The Author(s), 2017. Background Hypoxia is a characteristic of breast tumours indicating poor prognosis. Based on the assumption that those genes which are up-regulated under hypoxia in cell-lines are expected to be predictors of poor prognosis in clinical data, many signatures of poor prognosis were identified. However, it was observed that cell line data do not always concur with clinical data, and therefore conclusions from cell line analysis should be considered with caution. As many transcriptomic cell-line datasets from hypoxia related contexts are available, integrative approaches which investigate these datasets collectively, while not ignoring clinical data, are required. Results We analyse sixteen heterogeneous breast cancer cell-line transcriptomic datasets in hypoxia-related conditions collectively by employing the unique capabilities of the method, UNCLES, which integrates clustering results from multiple datasets and can address questions that cannot be answered by existing methods. This has been demonstrated by comparison with the state-of-the-art iCluster method. From this collection of genome-wide datasets include 15,588 genes, UNCLES identified a relatively high number of genes (>1000 overall) which are consistently co-regulated over all of the datasets, and some of which are still poorly understood and represent new potential HIF targets, such as RSBN1 and KIAA0195. Two main, anti-correlated, clusters were identified; the first is enriched with MYC targets participating in growth and proliferation, while the other is enriched with HIF targets directly participating in the hypoxia response. Surprisingly, in six clinical datasets, some sub-clusters of growth genes are found consistently positively correlated with hypoxia response genes, unlike the observation in cell lines. Moreover, the ability to predict bad prognosis by a combined signature of one sub-cluster of growth genes and one sub-cluster of hypoxia-induced genes appears to be comparable and perhaps greater than that of known hypoxia signatures. Conclusions We present a clustering approach suitable to integrate data from diverse experimental set-ups. Its application to breast cancer cell line datasets reveals new hypoxia-regulated signatures of genes which behave differently when in vitro (cell-line) data is compared with in vivo (clinical) data, and are of a prognostic value comparable or exceeding the state-of-the-art hypoxia signatures.Dr. Abu-Jamous would like to acknowledge the financial assistance from Brunel University London. Professors Buffa and Harris acknowledge support from Cancer Research UK, EU framework 7, and the Oxford NIHR Biomedical Research Centre. Professor Harris acknowledges support from the Breast Cancer Research Foundation. Professor Nandi would like to acknowledge that this work was partly supported by the National Science Foundation of China grant number 61520106006 and the National Science Foundation of Shanghai grant number 16JC1401300. The funding bodies have no role in the design of the study, in the collection, analysis, and interpretation of data, or in writing the manuscript

A novel approach for the selective analysis of L-lysine in untreated human serum by a co-crosslinked L-lysine–α-oxidase/overoxidized polypyrrole bilayer based amperometric biosensor

An amperometric biosensor based on an L-lysine-α-oxidase (LO) layer immobilized by co-crosslinking onto the surface of an overoxidized polypyrrole modified Pt electrode (Pt/oPPy) and able to analyse L-lysine (Lys) in untreated human serum is described. The sensing electrode has been characterised and a proper enzyme kinetics optimisation permits to use a low specific enzyme as LO from Trichoderma viride for the selective biorecognition of Lys in the presence of other interferent amino acids; a kinetics study of LO evidenced also the allosteric behaviour of this enzyme, a kinetic feature which was never reported before for this enzyme. The biosensor showed a sensitivity of 0.11 μA/mM mm2, linear responses up to 4 mM and a limit of detection of 2 μM; the within-a-day coefficients of variation for replicate (n = 5) were 0.92% and 1.35% at 4 mM and 0.2 mM Lys levels, respectively. The permselective behaviour of Pt/oPPy modified electrode assured an interference- and fouling-free determination of Lys even in untreated serum samples. The determination of Lys in human serum from healthy donors gave Lys levels in good agreement with the expected values so that the use of the proposed biosensor appears promising in the relevant clinical fields

Falsi ricordi per eventi emozionali: Il ruolo delle differenze individuali nella memoria di lavoro e nei tratti ansioso-depressivi

La nostra memoria \ue8 soggetta a distorsioni. Spesso ci serviamo dei nostri ricordi quando siamo in uno stato emotivo particolare e talvolta sono gli eventi stessi emotivamente carichi ad influenzare il recupero. Ricerche recenti suggeriscono che misure di working memory (WM) sono negativamente correlate alla produzione di falsi ricordi e che i tratti ansioso-depressivi favoriscono i falsi ricordi a valenza negativa. Il presente studio ha l\u2019obiettivo di studiare il ruolo delle differenze individuali in WM verbale e visuo-spaziale, memoria a breve termine (span di cifre) e stati affettivi (questionari per ansia, depressione e ruminazione) nella produzione di falsi ricordi emotivi. Studenti universitari (N=103) hanno partecipato allo studio. E\u2019 stato somministrato un paradigma di memoria di riconoscimento per fotografie (a valenza neutra, positiva o negativa) rappresentanti diversi script; esso consente di rilevare errori gap-filling (i.e., ricordare erroneamente un evento coerente con lo script) e causali (ricordare erroneamente la causa non vista dell\u2019effetto di un\u2019azione contenuta nello script). I risultati principali sono i seguenti: in generale, gli eventi da ricordare emotivamente carichi (positivi e negativi) proteggono gli individui dai falsi ricordi causali, rispetto agli eventi neutri. Inoltre, i gruppi con Bassa WM verbale e Basso span all\u2019indietro producono pi\uf9 errori causali negativi rispetto alle controparti Alta WM e Alta MBT. Un simile pattern di risultati si \ue8 verificato per il gruppo con Alti e Bassi tratti ansioso-depressivi. Infine, il gruppo Alta ruminazione produce un maggior numero di falsi ricordi rispetto al gruppo Bassa ruminazione. Importanti implicazioni pratiche per la testimonianza emergono da questo studio. Soprattutto, l\u2019importanza di considerare le differenze individuali in WM e MBT quando si deve valutare la memoria per eventi emotivamente carichi, cos\uec come la presenza di tratti ansioso-depressivi al momento della codifica degli eventi

Global stiffness and residual stresses in spinal fixator systems: A validated finite element study on the interconnection mechanism

Posterior spinal fixation systems are the gold standard to treat different column disorders using rods and screws. The proper connection between them is guaranteed by the Interconnection Mechanism (IM), consisting of different metallic subcomponents held together through the application of tightening torque. The response of the fixation system is defined by its overall stiffness, which in turn is governed by the local residual stress field arising during tightening. Although literature computational models for studying spinal fixation are becoming increasingly anatomically complex, most studies disregard completely the realistic modeling of the IM, namely choosing elastic-plastic material models and proper contact interactions. In this frame, the present study aims at increasing awareness in the field of spinal fixation modeling by investigating the mechanical response of the IM in terms of overall stiffness and local residual stresses. Once validated through dedicated experiments, the results of the proposed model have been compared with the current literature, highlighting the key role of the IM in the reliable modeling of spinal fixation

Collatamp sponges in the management of open fractures

Abstract. Open fractures are at high risk of infection and the prompt treatment of these injuries is critical to the success and is crucial to reduce the rate of complications.The basic steps of treatment include the immediate administration of systemic antibiotics, early surgical stabilization of the fracture associated with copious irrigation and radical debridement of the site of exposure, and when possible adequate soft tissue coverage. The systemic antibiotic therapy significantly improves the prognosis and reduces the occurrence of complications. However, in order to ensure adequate and sustained local concentration of antibiotic agent, high doses and for a long time are necessary. This increases the risk of side effects and bacterial resistance. The introduction of the antibiotic-loaded collagen sponges offers the advantages of a high local concentrations of antibiotic carrier delivering system with reduced systemic drug diffusion (less risk of side effects and resistance rate). Sponges are also biodegradable and fully resorbable and do not require additional surgery for their remova

Che cos'è terapeutico nel Therapeutic Residential Care? Come analizzare e sostenere la dimensione terapeutica nelle comunità residenziali [What is therapeutic in Therapeutic Residential Care? How to support and analyse the therapeutic dimension in residential care]

Il termine Therapeutic Residential Care (TRC) (Whittaker, del Valle e Holmes, 2014) indica le forme di accoglienza residenziale che si basano su un ambiente di vita intenzionalmente pensato per produrre cambiamento e migliorare le condizioni di vita di persone che presentano problematiche e bisogni specifici. Il presente articolo illustra i risultati parziali di una ricerca intervento realizzata in una comunità mamma-bambino dove si è applicato un metodo di lavoro a più componenti sviluppato per sostenere la funzione terapeutica degli interventi di comunità. Il metodo propone uno strumento di progettazione e valutazione basato su un processo di mentalizzazione di gruppo finalizzato alla costruzione di un pensiero e di una conoscenza condivisi dallo staff su ciascun utente.The term Therapeutic Residential Care (TRC) (Whittaker, del Valle, & Holmes, 2014) involves the planful use of a purposefully constructed, multi-dimensional living environment designed to enhance or provide treatment, education, socialization, support, and protection to children and youth with identified mental health or behavioral needs. The paper illustrates, through the example of its application in a mother-child unit, a multi-component working method developed to support the therapeutic function of residential care. The method proposes a planning and evaluation tool whose systematic use promotes a group mentalization process aimed at building a shared knowledge by the staff on each guest user, reducing the fragmentation of points of view and individual representations