Biomechanics of the distal radio-ulnar joint: A finite element study (biomeccanica dell'articolazione radio-ulnare distale: Studio agli elementi finiti)

Il metodo agli elementi finiti è stato utilizzato per valutare la distribuzione dei carichi e delle deformazioni in numerose componenti del corpo umano. L'applicazione di questo metodo ha avuto particolare successo nelle articolazioni con geometria semplice e condizioni di carico ben definite, mentre ha avuto un impatto minore sulla conoscenza della biomeccanica delle articolazioni multi-osso come il polso. Lo scopo di questo lavoro è quello di valutare gli aspetti clinici e biomeccanici dell’articolazione distale radio-ulnare, attraverso l’utilizzo di metodi di modellazione e di analisi agli elementi finiti. Sono stati progettati due modelli 3D a partire da immagini CT, in formato DICOM. Le immagini appartenevano ad un paziente con articolazione sana e ad un paziente con articolazione patologica, in particolare si trattava di una dislocazione ulnare traumatica. Le componenti principali dei modelli presi in considerazione sono stati: radio, ulna, cartilagine, legamento interosso, palmare e distale. Per la realizzazione del radio e dell’ulna sono stati utilizzati i metodi di segmentazione “Thresholding” e “RegionGrowing” sulle immagini e grazie ad operatori morfologici, è stato possibile distinguere l’osso corticale dall’osso spongioso. Successivamente è stata creata la cartilagine presente tra le due ossa, attraverso operazioni di tipo booleano. Invece, i legamenti sono stati realizzati prendendo i punti-nodo del radio e dell’ulna e formando le superfici tra di essi. Per ciascuna di queste componenti, sono state assegnate le corrispondenti proprietà dei materiali. Per migliorare la qualità dei modelli, sono state necessarie operazioni di “Smoothing” e “Autoremesh”. In seguito, è stata eseguita un’analisi agli elementi finiti attraverso l’uso di vincoli e forze, così da simulare il comportamento delle articolazioni. In particolare, sono stati simulati lo stress e la deformazione. Infine, grazie ai risultati ottenuti dalle simulazioni, è stato possibile verificare l’eventuale rischio di frattura in differenti punti anatomici del radio e dell’ulna nell’articolazione sana e patologica

Analysis of Intracellular Zn-Hydroxyapatite Nucleation in the Early Stages of Human Osteogenic Differentiation Combining Synchrotron-Based and Diffraction Techniques

The core knowledge about biomineralization is provided by studies on the advanced phases of the process mainly occurring in the extracellular matrix. This PhD project is based on the analysis of the early stages of biomineralization by evaluating the chemical fingerprint of the initial mineral nuclei deposition in the intracellular milieu and their evolution toward hexagonal hydroxyapatite. The study is conducted on human bone mesenchymal stem cells (bMSC) exposed to an osteogenic cocktail for 4 and 10 days, exploiting laboratory X-ray diffraction techniques and cutting-edge developments of synchrotron based 2D and 3D cryo X-ray microscopy. The synchrotron-based phase contrast imaging revealed few small intracellular depositions @4th day of differentiation and a lot of extracellular and intracellular mineral nuclei @10th day. The 3D reconstructions of phase-contrast images of bMSC at 10 days allowed browsing the entire cell along its thickness to explore the three-dimensional localization of the mineral depositions. Several spots are localized in the cytoplasm of the cell, indicating that the biomineralization starts in the intracellular environment. Synchrotron X-ray Fluorescence Microscopy was carried out to determine the chemical composition of mineral nuclei formation at nanoscale, confirming that mineral accumulation starts early during the osteogenic differentiation of bMSC and providing experimental evidence about the Zn role in HA nucleation. The X-ray fluorescence tomography was performed to obtain the 3D visualization of Ca, P and Zn elemental distribution. Wide/Small Angle X-ray Scattering and X-ray Absorption Near-Edge Spectroscopy revealed the hexagonal HA as the unique crystalline structure present in differentiating bMSC. In conclusion, thanks to the combination of 3D high-resolution synchrotron-based X-ray techniques, it has been demonstrated that biomineralization starts with hydroxyapatite nucleation in the intracellular environment, rapidly evolving toward a hexagonal hydroxyapatite crystal very similar to the one present in human bone as detected after just ten days of osteogenic induction

Blood CXCR3(+) CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals

We recently demonstrated that lymph nodes (LNs) PD-1+/T follicular helper (Tfh) cells from antiretroviral therapy (ART)-treated HIV-infected individuals were enriched in cells containing replication competent virus. However, the distribution of cells containing inducible replication competent virus has been only partially elucidated in blood memory CD4 T-cell populations including the Tfh cell counterpart circulating in blood (cTfh). In this context, we have investigated the distribution of (1) total HIV-infected cells and (2) cells containing replication competent and infectious virus within various blood and LN memory CD4 T-cell populations of conventional antiretroviral therapy (cART)-treated HIV-infected individuals. In the present study, we show that blood CXCR3-expressing memory CD4 T cells are enriched in cells containing inducible replication competent virus and contributed the most to the total pool of cells containing replication competent and infectious virus in blood. Interestingly, subsequent proviral sequence analysis did not indicate virus compartmentalization between blood and LN CD4 T-cell populations, suggesting dynamic interchanges between the two compartments. We then investi-gated whether the composition of blood HIV reservoir may reflect the polarization of LN CD4 T cells at the time of reservoir seeding and showed that LN PD-1+ CD4 T cells of viremic untreated HIV-infected individuals expressed significantly higher levels of CXCR3 as compared to CCR4 and/or CCR6, suggesting that blood CXCR3-expressing CD4 T cells may originate from LN PD-1+ CD4 T cells. Taken together, these results indicate that blood CXCR3-expressing CD4 T cells represent the major blood compartment con-taining inducible replication competent virus in treated aviremic HIV-infected individuals

Clinical efficacy of Enzyme Replacement Therapy in paediatric Hunter patients, an independent study of 3.5 years

BACKGROUND: Hunter Syndrome is an X-linked lysosomal storage disorder due to the deficit of iduronate 2-sulfatase, an enzyme catalysing the degradation of the glycosaminoglycans (GAG) dermatan- and heparan-sulfate. Treatment of the disease is mainly performed by Enzyme Replacement Therapy (ERT) with idursulfase, in use since 2006. Clinical efficacy of ERT has been monitored mainly by the Hunter Outcome Survey (HOS) while very few independent studies have been so far conducted. The present study is a 3.5-years independent follow-up of 27 Hunter patients, starting ERT between 1.6 and 27 years of age, with the primary aim to evaluate efficacy of the therapy started at an early age (<12 years). METHODS: In this study, we evaluated: urinary GAG content, hepato/splenomegaly, heart valvulopathies, otorinolaryngological symptoms, joint range of motion, growth, distance covered in the 6-minute walk test, neurological involvement. For data analysis, the 27 patients were divided into three groups according to the age at start of ERT: ≤5 years, >5 and ≤ 12 years and > 12 years. Patients were analysed both as 3 separate groups and also as one group; in addition, the 20 patients who started ERT up to 12 years of age were analysed as one group. Finally, patients presenting a “severe” phenotype were compared with “attenuated” ones. RESULTS: Data analysis revealed a statistically significant reduction of the urinary GAG in patients ≤5 years and ≤ 12 years and of the hepatomegaly in the group aged >5 and ≤ 12 years. Although other clinical signs improved in some of the patients monitored, statistical analysis of their variation did not reveal any significant changes following enzyme administration. The evaluation of ERT efficacy in relation to the severity of the disease evidenced slightly higher improvements as for hepatomegaly, splenomegaly, otological disorders and adenotonsillar hypertrophy in severe vs attenuated patients. CONCLUSIONS: Although the present protocol of idursulfase administration may result efficacious in delaying the MPS II somatic disease progression at some extent, in this study we observed that several signs and symptoms did not improve during the therapy. Therefore, a strict monitoring of the efficacy obtained in the patients under ERT is becoming mandatory for clinical, ethical and economic reasons. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-014-0129-1) contains supplementary material, which is available to authorized users

Predictors of long-term response to abiraterone in patients with metastastic castration-resistant prostate cancer: a retrospective cohort study

We aimed to identify clinical predictors of long-term response to abiraterone (defined as &gt;12 months drug exposure) in a retrospective cohort of metastatic castration-resistant prostate cancer patients treated in post-docetaxel setting at 24 Italian centers. The Cox proportional hazards model was used to analyze the association between clinical features and the duration of drug exposure. Results were expressed as hazard ratios (HR) with associated 95% confidence intervals (CI). A total of 143 patients met the inclusion criteria. Their median age was 73 years, median Gleason score 8 and median abiraterone exposure 20 months. At the univariate analysis, a significant correlation with the duration of abiraterone exposure was found for Gleason score (HR 0.82, 95% CI 0.71-0.96; p=0.012), PSA (HR 1.10, 95% CI 1.03-1.18; p=0.08) and lactic dehydrogenase levels (HR 1.22, 95% CI 1.02-1.46; p=0.027), while the association between lower alkaline phosphatase levels and treatment duration was marginally significant (HR 1.07, 95% CI 0.99-1.16; p=0.074). Only PSA and Gleason score were predictive of long-term treatment duration in the multivariate analysis. No other clinical factors resulted to be predictive of sustained response to abiraterone, including metastatic disease at diagnosis and visceral disease, suggesting that all subgroups of patients may derive a substantial clinical benefit from abiraterone treatment. These findings need to be validated in prospective, larger studies

The prognostic value of the previous nephrectomy in pretreated metastatic renal cell carcinoma receiving immunotherapy: a sub-analysis of the Meet-URO 15 study

Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era

Natural History of Malignant Bone Disease in Renal Cancer: Final Results of an Italian Bone Metastasis Survey

Abstract Background: Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as diseaserelated survival improves. There are few data on the natural history of bone disease in RCC

El mito de Ulises en el teatro español contemporáneo

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Filosofía y Letras, Departamento de Filología Española. Fecha de lectura: 19-10-201

New formulation of the Navier–Stokes equations for liquid flows

For isothermal liquid flows, the condition of incompressibility provides a useful simplification for describing their mechanical properties. Nevertheless, it overlooks acoustic effects, and it provides the unpleasant shortcoming of infinite propagation speed of velocity perturbations, no matter the type of constitutive equation for the shear stresses is adopted. In this paper, we provide a derivation of a new formulation of the Navier–Stokes equations for liquid flows that overcomes the above issues. The pressure looses its ancillary status of mere gauge variable (or equivalently Lagrange multiplier of the incompressibility condition) enforcing the solenoidal nature of the velocity field, and attains the proper physical meaning of hydrodynamic field variable characterized by its own spatiotemporal evolution. From the experimental evidence of sound attenuation, related to the occurrence of a non-vanishing bulk viscosity, the evolution equation for pressure in out-of-equilibrium conditions is derived without introducing any adjustable parameters. The connection between compressibility and memory effects in the propagation of internal stresses is established. Normal mode analysis and some preliminary simulations are also discussed

Comparison between one- and two-way coupling approaches for estimating effective transport properties of suspended particles undergoing Brownian sieving hydrodynamic chromatography

Simplified one-way coupling approaches are often used to model transport properties of diluted particle suspensions for predicting the performance of microcapillary hydrodynamic chromatography (MHDC). Recently, a one-way coupling approach was exploited to optimize the geometry and operating conditions of an unconventional double-channel geometry with a square cross-section, where a Brownian sieving mechanism acting alongside the MHDC separation drive (BS-MHDC) is enforced to boost separation resolution. In this article, a cylindrical geometry enforcing the same BS-MHDC separation drive is thoroughly investigated by following a two-way coupling, fully three-dimensional approach, and results are compared with those obtained enforcing the one-way coupling analysis. Device geometry and operating conditions are optimized by maximizing the separation resolution. The effective velocity and dispersion coefficient of spherical, finite-sized particles of different diameters are computed, and two-phase effects are discussed in detail. Similar to the square channel device, the cylindrical double-channel geometry allows for a sizable reduction in the column length and in the analysis time (a factor above 12 for the length and a factor larger than 3 for the processing time) when compared to the standard MHDC configuration ensuring the same separation resolution. As expected, the one-way coupling approach overestimates the separation performance of both the BS-MHDC and the standard MHDC devices with respect to the two-way coupling analysis. But, surprisingly, the enhancement factor of the BS-MHDC over the standard MHDC is underestimated by the single-phase approximation as it doubles when wall/particle interactions are properly accounted for with a two-phase description