Additive manufactured, highly resilient, elastic, and biodegradable poly(ester)urethane scaffolds with chondroinductive properties for cartilage tissue engineering

Articular cartilage was thought to be one of the first tissues to be successfully engineered. Despite the avascular and non-innervated nature of the tissue, the cells within articular cartilage - chondrocytes - account for a complex phenotype that is difficult to be maintained in vitro. The use of bone marrow-derived stromal cells (BMSCs) has emerged as a potential solution to this issue. Differentiation of BMSCs toward stable and non-hypertrophic chondrogenic phenotypes has also proved to be challenging. Moreover, hyaline cartilage presents a set of mechanical properties - relatively high Young's modulus, elasticity, and resilience - that are difficult to reproduce. Here, we report on the use of additive manufactured biodegradable poly(ester)urethane (PEU) scaffolds of two different structures (500 mu m pore size and 90 degrees or 60 degrees deposition angle) that can support the loads applied onto the knee while being highly resilient, with a permanent deformation lower than 1% after 10 compression-relaxation cycles. Moreover, these scaffolds appear to promote BMSC differentiation, as shown by the deposition of glycosaminoglycans and collagens (in particular collagen II). At gene level, BMSCs showed an upregulation of chondrogenic markers, such as collagen II and the Sox trio, to higher or similar levels than that of traditional pellet cultures, with a collagen II/collagen I relative expression of 2-3, depending on the structure of the scaffold. Moreover, scaffolds with different pore architectures influenced the differentiation process and the final BMSC phenotype. These data suggest that additive manufactured PEU scaffolds could be good candidates for cartilage tissue regeneration in combination with microfracture interventions.</p

Quality of Life and psychopathology in adults who underwent Hematopoietic Stem Cell Transplantation (HSCT) in childhood: a qualitative and quantitative analysis.

Background: Patients who undergo pediatric Hematopoietic Stem Cell Transplantation (HSCT) may experience long-term psychological sequelae and poor Quality of Life (QoL) in adulthood. This study aimed to investigate subjective illness experience, QoL, and psychopathology in young adults who have survived pediatric HSCT. Method: The study involved patients treated with HSCT in the Hematology-Oncology Department between 1984 and 2007. Psychopathology and QoL were investigated using the SCL-90-R and SF-36. Socio-demographic and medical information was also collected. Finally, participants were asked to write a brief composition about their experiences of illness and care. Qualitative analysis of the texts was performed using T-LAB, an instrument for text analysis that allows the user to highlight the occurrences and co-occurrences of lemma. Quantitative analyses were performed using non-parametric tests (Spearman correlations, Kruskal-Wallis and Mann-Whitney tests). Results: Twenty-one patients (9 males) participated in the study. No significant distress was found on the SCL-90 Global Severity Index, but it was found on specific scales. On the SF-36, lower scores were reported on scales referring to bodily pain, general health, and physical and social functioning. All the measures were significantly (p < 0.05) associated with specific socio-demographic and medical variables (gender, type of pathology, type of HSCT, time elapsed between communication of the need to transplant and effective transplantation, and days of hospitalization). With regard to the narrative analyses, males focused on expressions related to the body and medical therapies, while females focused on people they met during treatment, family members, and donors. Low general health and treatment with autologous HSCT were associated with memories about chemotherapy, radiotherapy, and the body parts involved, while high general health was associated with expressions focused on gratitude (V-Test \ub1 1.96). Conclusion: Pediatric HSCT survivors are more likely to experience psychological distress and low QoL in adulthood compared with the general population. These aspects, along with survivors' subjective illness experience, show differences according to specific medical and socio-demographic variables. Studies are needed in order to improve the care and long-term follow-up of these families

Investigating the gamma-ray burst from decaying MeV-scale axion-like particles produced in supernova explosions

We investigate the characteristics of the gamma-ray signal following the decay of MeV-scale Axion-Like Particles (ALPs) coupled to photons which are produced in a Supernova (SN) explosion. This analysis is the first to include the production of heavier ALPs through the photon coalescence process, enlarging the mass range of ALPs that could be observed in this way and giving a stronger bound from the observation of SN 1987A. Furthermore, we present a new analytical method for calculating the predicted gamma-ray signal from ALP decays. With this method we can rigorously prove the validity of an approximation that has been used in some of the previous literature, which we show here to be valid only if all gamma rays arrive under extremely small observation angles (i.e. very close to the line of sight to the SN). However, it also shows where the approximation is not valid, and offers an efficient alternative to calculate the ALP-induced gamma-ray flux in a general setting when the observation angles are not guaranteed to be small. We also estimate the sensitivity of the Fermi Large Area Telescope (Fermi-LAT) to this gamma-ray signal from a future nearby SN and show that in the case of a non-observation the current bounds on the ALP-photon coupling $g_{a\gamma}$ are strengthened by about an order of magnitude. In the case of an observation, we show that it may be possible to reconstruct the product $g_{a\gamma}^2 m_a$, with $m_a$ the mass of the ALP.Comment: 28 pages, 9 figure

Global analysis of the pMSSM in light of the Fermi GeV excess: prospects for the LHC Run-II and astroparticle experiments

We present a new global fit of the 19-dimensional phenomenological Minimal Supersymmetric Standard Model (pMSSM-19) that comply with all the latest experimental results from dark matter indirect, direct and accelerator dark matter searches. We show that the model provides a satisfactory explanation of the excess of gamma-rays from the Galactic centre observed by the Fermi~Large Area Telescope, assuming that it is produced by the annihilation of neutralinos in the Milky Way halo. We identify two regions that pass all the constraints: the first corresponds to neutralinos with a mass ~80-100 GeV annihilating into WW with a branching ratio of 95% ; the second to heavier neutralinos, with mass ~180-200 GeV annihilating into t tbar with a branching ratio of 87%. We show that neutralinos compatible with the Galactic centre GeV excess will soon be within the reach of LHC run-II -- notably through searches for charginos and neutralinos, squarks and light smuons -- and of Xenon1T, thanks to its unprecedented sensitivity to spin-dependent cross-section off neutrons.Comment: Minor changes following referee reports. Main conclusions unchanged. Matches version published in JCA

Short-Term Bisphosphonate Therapy Could Ameliorate Osteonecrosis: A Complication in Childhood Hematologic Malignancies

Osteonecrosis (ON) is a critical complication in the treatment of childhood leukemia and lymphoma. It particularly affects survivors of acute lymphoblastic leukemia and non-Hodgkin lymphoma reflecting the cumulative exposure to glucocorticosteroid therapy. ON is often multiarticular and bilateral, specially affecting weight-bearing joints. A conventional approach suggests a surgical intervention even if pharmacological options have also recently been investigated. We reported two cases of long time steroid-treated patients who underwent Bone Marrow Transplantation (BMT) for hematological disease. Both patients developed femoral head osteonecrosis (ON) that was diagnosed by magnetic resonance imaging (MRI) and the ON was also accompanied with pain and a limp. Despite of the conventional strategies of therapy, we successfully started a short-term treatment with bisphosphonates in order to decrease the pain and the risk of fracture

An INTEGRAL/SPI view of reticulum II: Particle dark matter and primordial black holes limits in the MeV range

© 2022 The Author(s) Published by Oxford University Press on behalf of Royal Astronomical Society. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1093/mnras/stac008Reticulum II (Ret II) is a satellite galaxy of the Milky Way and presents a prime target to investigate the nature of dark matter (DM) because of its high mass-to-light ratio. We evaluate a dedicated INTEGRAL observation campaign data set to obtain $\gamma$-ray fluxes from Ret II and compare those with expectations from DM. Ret II is not detected in the $\gamma$-ray band 25--8000 keV, and we derive a flux limit of $\lesssim 10^{-8}\,\mathrm{erg\,cm^{-2}\,s^{-1}}$. The previously reported 511 keV line is not seen, and we find a flux limit of $\lesssim 1.7 \times 10^{-4}\,\mathrm{ph\,cm^{-2}\,s^{-1}}$. We construct spectral models for primordial black hole (PBH) evaporation and annihilation/decay of particle DM, and subsequent annihilation of positrons produced in these processes. We exclude that the totality of DM in Ret II is made of a monochromatic distribution of PBHs of masses $\lesssim 8 \times 10^{15}\,\mathrm{g}$. Our limits on the velocity-averaged DM annihilation cross section into $e^+e^-$ are $\langle \sigma v \rangle \lesssim 5 \times 10^{-28} \left(m_{\rm DM} / \mathrm{MeV} \right)^{2.5}\,\mathrm{cm^3\,s^{-1}}$. We conclude that analysing isolated targets in the MeV $\gamma$-ray band can set strong bounds on DM properties without multi-year data sets of the entire Milky Way, and encourage follow-up observations of Ret II and other dwarf galaxies.Peer reviewedFinal Accepted Versio

Clinical and functional characterization of a novel mutation in lamin a/c gene in a multigenerational family with arrhythmogenic cardiac laminopathy.

none17noneAkinori Kimura;Cinzia Forleo;Monica Carmosino;Nicoletta Resta;Alessandra Rampazzo;Rosanna Valecce;Sandro Sorrentino;Massimo Iacoviello;Francesco Pisani;Giuseppe Procino;Andrea Gerbino;Arnaldo Scardapane;Cristiano Simone;Martina Calore;Silvia Torretta;Maria Svelto;Stefano FavaleAkinori, Kimura; Cinzia, Forleo; Monica, Carmosino; Nicoletta, Resta; Rampazzo, Alessandra; Rosanna, Valecce; Sandro, Sorrentino; Massimo, Iacoviello; Francesco, Pisani; Giuseppe, Procino; Andrea, Gerbino; Arnaldo, Scardapane; Cristiano, Simone; Calore, Martina; Silvia, Torretta; Maria, Svelto; Stefano, Faval

BK virus associated meningoencephalitis in an AIDS patient treated with HAART

A severely immune-suppressed AIDS patient was suspected of suffering from BK virus (BKV) meningoencephalitis, after being studied for common causes of neurological complications of co-infectious origin. Polymerase chain reaction (PCR) and sequence analysis of cerebrospinal fluid and brain samples, confirmed the presence of BKV. His clinical condition improved along with the regression of brain lesions, after modifications on his antiretroviral regime. Five months after discharge, the patient was readmitted because of frequent headaches, and a marked inflammatory reaction was evidenced by a new magnetic resonance imaging (MRI). The symptoms paralleled a rising CD4+ lymphocyte count, and immune reconstitution syndrome was suspected. This is the first non-postmortem report of BKV meningoencephalitis in an AIDS patient, showing clinical and radiographic improvement solely under HAART