Treatment responses to antiangiogenetic therapy and chemotherapy in nonsecreting paraganglioma (PGL4) of urinary bladder with SDHB mutation: a case report

Paraganglioma (PGL) is a rare neuroendocrine tumor. Currently, the malignancy is defined as the presence of metastatic spread at presentation or during follow-up. Several gene mutations are listed in the pathogenesis of PGL, among which succinate dehydrogenase (SDHX), particularly the SDHB isoform, is the main gene involved in malignancy. A 55-year-old male without evidence of catecholamine secretion had surgery for PGL of the urinary bladder. After 1 year, he showed a relapse of disease and demonstrated malignant PGL without evidence of catecholamine secretion with a germline heterozygous mutation of succinate dehydrogenase B (SDHB). After failure of a second surgery for relapse, he started medical treatment with sunitinib daily but discontinued due to serious side effects. Cyclophosphamide, vincristine, and dacarbazine (CVD) chemotherapeutic regimen stopped the disease progression for 7 months. Conclusion: Malignant PGL is a very rare tumor, and SDHB mutations must be always considered in molecular diagnosis because they represent a critical event in the progression of the oncological disease. Currently, there are few therapeutic protocols, and it is often difficult, as this case demonstrates, to decide on a treatment option according to a reasoned set of choices. Abbreviations: CVD = cyclophosphamide, vincristine and dacarbazine, HIF-1a = hypoxia inducible factor 1 alpha, PGL = paraganglioma, SDH = succinate dehydrogenase, VEGF = vasoendothelial growth factor

First steps to define murine amniotic fluid stem cell microenvironment

Stem cell niche refers to the microenvironment where stem cells reside in living organisms. Several elements define the niche and regulate stem cell characteristics, such as stromal support cells, gap junctions, soluble factors, extracellular matrix proteins, blood vessels and neural inputs. In the last years, different studies demonstrated the presence of cKit+ cells in human and murine amniotic fluid, which have been defined as amniotic fluid stem (AFS) cells. Firstly, we characterized the murine cKit+ cells present both in the amniotic fluid and in the amnion. Secondly, to analyze the AFS cell microenvironment, we injected murine YFP+ embryonic stem cells (ESC) into the amniotic fluid of E13.5 wild type embryos. Four days after transplantation we found that YFP+ sorted cells maintained the expression of pluripotency markers and that ESC adherent to the amnion were more similar to original ESC in respect to those isolated from the amniotic fluid. Moreover, cytokines evaluation and oxygen concentration analysis revealed in this microenvironment the presence of factors that are considered key regulators in stem cell niches. This is the first indication that AFS cells reside in a microenvironment that possess specific characteristics able to maintain stemness of resident and exogenous stem cells

Constraints on new physics from the quark mixing unitarity triangle

The status of the Unitarity Triangle beyond the Standard Model including the most recent results on Delta m_s, on dilepton asymmetries and on width differences is presented. Even allowing for general New Physics loop contributions the Unitarity Triangle must be very close to the Standard Model result. With the new measurements from the Tevatron, we obtain for the first time a significant constraint on New Physics in the B_s sector. We present the allowed ranges of New Physics contributions to Delta F=2 processes, and of the time-dependent CP asymmetry in B_s to J/Psi phi decays.Comment: 5 pages, 4 figures. v2: numerical error in Delta Gamma_s/Gamma_s corrected. Plots and tables updated. v3: update after ICHEP06, final version published in Phys Rev Letter

Exploratory analysis of transposable elements expression in the C. elegans early embryo

Background: Transposable Elements (TE) are mobile sequences that make up large portions of eukaryote genomes. The functions they play within the complex cellular architecture are still not clearly understood, but it is becoming evident that TE have a role in several physiological and pathological processes. In particular, it has been shown that TE transcription is necessary for the correct development of mice embryos and that their expression is able to finely modulate transcription of coding and non-coding genes. Moreover, their activity in the central nervous system (CNS) and other tissues has been correlated with the creation of somatic mosaicisms and with pathologies such as neurodevelopmental and neurodegenerative diseases as well as cancers. Results: We analyzed TE expression among different cell types of the Caenorhabditis elegans (C. elegans) early embryo asking if, where and when TE are expressed and whether their expression is correlated with genes playing a role in early embryo development. To answer these questions, we took advantage of a public C. elegans embryonic single-cell RNA-seq (sc-RNAseq) dataset and developed a bioinformatics pipeline able to quantify reads mapping specifically against TE, avoiding counting reads mapping on TE fragments embedded in coding/non-coding transcripts. Our results suggest that i) canonical TE expression analysis tools, which do not discard reads mapping on TE fragments embedded in annotated transcripts, may over-estimate TE expression levels, ii) Long Terminal Repeats (LTR) elements are mostly expressed in undifferentiated cells and might play a role in pluripotency maintenance and activation of the innate immune response, iii) non-LTR are expressed in differentiated cells, in particular in neurons and nervous system-Associated tissues, and iv) DNA TE are homogenously expressed throughout the C. elegans early embryo development. Conclusions: TE expression appears finely modulated in the C. elegans early embryo and different TE classes are expressed in different cell types and stages, suggesting that TE might play diverse functions during early embryo development

Long-term results after modified Burton-Pellegrini’s technique in 24 cases affected by advanced rhizarthrosis

Background and aim: Rhizarthrosis iscommon in elderly and represents 10% of all artrhitic manifestations. Trapeziectomy with ligament reconstruction and tendon interposition remains the gold standard for stages II to IV according to Eaton and Littler. This retrospective study aimed to evaluate the results of 24 patients affected by advanced rhizarthrosis who underwent to modified Burton-Pellegrini’s trapeziectomy with ligamentoplasty using the entire flexor carpi radialis tendon. Methods: Patients were assessed through DASH and PRWHE questionnaires; the examination focused also on pain symptoms (VAS score) and the results obtained in carrying out specific tests to evaluate the trapezius-metacarpal functionality (key-pinch, grip strength, Kapandji test, reduction of wrist flexion strength). Furthermore, postoperative complications were evaluated. Results: Clinical evaluation and individual satisfaction were positive in most cases (mean DASH 18,8 and mean PRWHE 21,7). VAS pain score reduced of 76.7%, grip strength and key pinch were similar to those of the non-operated hand and Kapandji test was excellent in 20 patients. One superficial wound infection was encountered which resolved by specific antibiotic therapy. Conclusions: The choice of the most appropriate treatment depends on clinical conditions and socio-occupational factors of the patient (age, sex and functional needs), the degree of osteoarthritis and the presence of deformities of the first metacarpophalangeal joint. Surgery aims to relief pain and to improve joint function and strength. According to the results observed this surgical technique has to be considered a valid option for the treatment of advanced rhizarthrosis as it provides pain relief, stability and mobility of the thumb. (www.actabiomedica.it)

Dair approach in 7 infected total hip arthroplasties: our experience and current concepts of the literature

INTRODUCTION: Periprosthetic joint infection (PJI) is one of the most challenging complications following total hip arthroplasty. In early infection, within four to twelve weeks from surgery, debridement, antibiotics and implant retention (DAIR) can be the initial treatment. The aim of this study is to report our case series and review current concepts reported in the literature about this topic. MATERIALS AND METHODS: This was an observational cohort study that included 7 patients managed with DAIR for PJI following primary total hip replacement (THR) between 2014 and 2020. Inclusion criteria were a primary THR, direct anterior or lateral approach, DAIR procedure, and PJI. Exclusion criteria were a PJI following a revision total hip replacement or hemiarthroplasty, posterolateral approach, 1-stage revision, 2-stage revision, and Girdlestone procedure without prior DAIR. For each patient demographic characteristics, laboratory values, microorganisms involved, antibiotic therapy and outcome at one-year follow-up were registered. RESULTS: The mean duration between THR and DAIR was 19 days. In all cases only one DAIR procedure was performed. Most infections were caused by Staphylococcus aureus (4 cases) [one methicillin resistant (MRSA)]. The other infections were caused by Streptococcus agalactiae, Staphylococcus coagulase negative and Escherichia coli. At the final follow-up, the procedure was considered as successful in 6 out of 7 patients (85%). The one with unsuccessful outcome underwent to a two-stage revision. DISCUSSION: Our results were comparable with those of a recent systematic review of the literature. Factors that have been postulated to influence the outcome of DAIR in the management of PJIs include the timing and numbers of debridement, the exchange of components, the responsible microorganism and the duration of antibiotic treatment. In conclusion, the outcomes following DAIR are better as the indications are refined and risk factors identified. PJI prevention remains the key but the current literature still lacks well documented and effective PJI prevention protocols. (www.actabiomedica.it)

Digital light processing stereolithography of hydroxyapatite scaffolds with bone-like architecture, permeability, and mechanical properties

This work deals with the additive manufacturing and characterization of hydroxyapatite scaffolds mimicking the trabecular architecture of cancellous bone. A novel approach was proposed relying on stereolithographic technology, which builds foam-like ceramic scaffolds by using three-dimensional (3D) micro-tomographic reconstructions of polymeric sponges as virtual templates for the manufacturing process. The layer-by-layer fabrication process involves the selective polymerization of a photocurable resin in which hydroxyapatite particles are homogeneously dispersed. Irradiation is performed by a dynamic mask that projects blue light onto the slurry. After sintering, highly-porous hydroxyapatite scaffolds (total porosity ~0.80, pore size 100-800 µm) replicating the 3D open-cell architecture of the polymeric template as well as spongy bone were obtained. Intrinsic permeability of scaffolds was determined by measuring laminar airflow alternating pressure wave drops and was found to be within 0.75-1.74 × 10−9m2, which is comparable to the range of human cancellous bone. Compressive tests were also carried out in order to determine the strength (~1.60 MPa), elastic modulus (~513 MPa) and Weibull modulus (m = 2.2) of the scaffolds. Overall, the fabrication strategy used to print hydroxyapatite scaffolds (tomographic imaging combined with digital mirror device [DMD]-based stereolithography) shows great promise for the development of porous bioceramics with bone-like architecture and mass transport properties

Metrological characterization of MEMS accelerometers by LDV

Abstract In this work two calibration methodologies, able to characterize the digital sensitivity of MEMS accelerometers, are presented and compared, to identify the contributions for the evaluation of the reproducibility in the low frequency range. The methodologies are different from the point of view of test bench, test procedure and data processing method. In particular, different vibration actuators are used, a linear slide and an electro-dynamic shaker, different sensors as a reference for the calibration, piezoelectric accelerometers and a Laser Doppler Vibrometer (LDV). A group of 5 accelerometers is tested for the purpose of developing the calibration techniques and evaluate a first reproducibility estimate. The experimental results provided by the two calibration procedures show significant differences. Some elements that could explain these differences have been identified, and will be further investigated in future work

Characterisation of the secondary-neutron production in particle therapy treatments with the MONDO tracking detector

Particle Therapy (PT) is a non-invasive technique that exploits charged light ions for the irradiation of tumours that cannot be effectively treated with surgery or conventional radiotherapy. While the largest dose fraction is released to the tumour volume by the primary beam, a non-negligible amount of additional dose is due to the beam fragmentation that occurs along the path towards the target volume. In particular, the produced neutrons are particularly dangerous as they can release their energy far away from the treated area, increasing the risk of developing a radiogenic secondary malignant neoplasm after undergoing a treatment. A precise measurement of the neutron flux, energy spectrum and angular distributions is eagerly needed in order to improve the treatment planning system software, so as to predict the normal tissue toxicity in the target region and the risk of late complications in the whole body. The MONDO (MOnitor for Neutron Dose in hadrOntherapy) project is dedicated to the characterisation of the secondary ultra-fast neutrons ([20-400] MeV energy range) produced in PT. The neutron tracking system exploits the reconstruction of the recoil protons produced in two consecutive (n, p) elastic scattering interactions to measure simultaneously the neutron incoming direction and energy. The tracker active media is a matrix of thin squared scintillating fibers arranged in orthogonally oriented layers that are read out by a sensor (SBAM) based on SPAD (Single-Photon Avalanche Diode) detectors developed in collaboration with the Fondazione Bruno Kessler (FBK)

Efficacy and safety of viscosupplementation with hyaluronic acid for hip osteoarthritis: Results from a cross-sectional study with a minimum follow-up of 4 years

Background and aim of the work: Osteoarthritis is the most common cause of disability in elderly. Hip osteoarthritis is the second most frequent form affecting a large joint and the social and economic impact on society of its related disability is expected to increase. The purpose of this study was to verify the efficacy and safety of ultrasound-guided viscosupplementation with high weight hyaluronic acid in hip osteoarthritis. Methods: 183 patients with painful hip OA (Kellgren-Lawrence 1-2-3) were treated from January 2014 to December 2016 with viscosupplementation. Patients were evaluated before injection (T0) and after 1,2,3,4 (T1-T2-T3-T4) years through the VAS scale and Harris Hip Score (HHS). Patients who underwent to subsequent injections were followed and assessed. Subjects who underwent prosthesis were analyzed for a minimum of 6 months in order to detect any early postoperative complication. Results: The mean improvement of HHS and VAS between T0 and T1 was statistically significant. Patients who underwent subsequent injections showed a higher improvement even if statistical significance was not observed. Results showed that patients with grade 2 of osteoarthritis had the higher change in the scores. No adverse effects were registered. No early complications were reported in those patients who needed prosthesis. Discussion and Conclusions: Results observed confirm that ultrasound-guided viscosupplementation with high weight hyaluronic acid could be a possibility in the treatment of hip osteoarthritis, especially in patients with Kellgren-Lawrence grade 2 of disease. Subsequent injections are not characterized by similar positive effects. Outcomes of pros-thetic surgery are not influenced by viscosupplementation