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

Cryo-mechanical treatment and hydrometallurgical process for recycling Li-MnO2primary batteries with the direct production of LiMnPO4nanoparticles

In this work, an innovative hydrometallurgical recycling route for the recovery of all the materials composing Li-MnO2 primary batteries was proposed. End-of-life batteries were mechanically treated in an innovative pilot plant where a cryogenic crushing was performed. The mechanical treatment allowed for the release of the electrodic powder contained in the batteries with the simultaneous recovery of 44 kg of steel and 18 kg of plastics from 100 kg of batteries. Electrodic powder was employed as the raw material for the synthesis of LiMnPO4 nanoparticles. To obtain the synthesis precursors, selective sequential leaching of Li and Mn was performed. Li was extracted via water washing the electrodic powder and Li2CO3 and a purity of 99% was recovered. The black mass containing Mn oxides was leached using phosphoric acid, which gave a Mn-bearing precursor solution that was directly used for the hydrothermal synthesis of LiMnPO4 nanoparticles. A preliminary materials balance of the process was presented, indicating that the proposed process should be an easy hydrometallurgical route for the recycling of primary lithium batteries. In addition, the simultaneous production of high-value-added products that could be reintroduced into the battery manufacturing chain could ensure the economic feasibility of the process

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

The major allergen of the Parietaria pollen contains an LPS-binding region with immuno-modulatory activity

Background: The major allergens in Parietaria pollen, Par j 1 and Par j 2, have been identified as lipid transfer proteins. The family of the Par j 1 allergens is composed of two isoforms, which differ by the presence of a 37 amino acid peptide (Par37) exclusive to the Par j 1.0101 isoform. The goal of this study was to elucidate the biological properties of the Par37 peptide. Methods: In silico analysis, spectrofluorimetric experiments and in vitro cell culture assays were used to identify the biological properties of Par37. In addition, a mouse model of sensitization was used to study the influence of Par37 in the murine immune response. Results: In silico analysis predicted that Par37 displays characteristics of a host defence peptide. Spectrofluorimetric analysis, real-time PCR and ELISA assays demonstrated that Par37 possesses an LPS-binding activity influencing cell signalling in vitro. In RAW264.7 cells, LPS-induced IL-6 and TNF-a transcription and translation were inhibited after preincubation with Par37. Consistent with these data, inhibition of IFN-c secretion was observed in murine spleen cells and in human PBMC. Finally, mice immunized with the two Par j 1 isoforms differing in the presence or absence of the Par37 peptide showed different immunological behaviours in vivo. Conclusions: This study demonstrates that the Par j 1.0101 allergen displays LPSbinding activity due to the presence of a 37 amino acid COOH-terminal region and that this region is capable of influencing cytokine and antibody responses in vitro and in vivo

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

Mimicking human riboflavin responsive neuromuscular disorders by silencing flad-1 gene in C. elegans: Alteration of vitamin transport and cholinergic transmission

Riboflavin (Rf), or vitamin B2, is the precursor of FMN and FAD, redox cofactors of several dehydrogenases involved in energy metabolism, redox balance and other cell regulatory processes. FAD synthase, coded by FLAD1 gene in humans, is the last enzyme in the pathway converting Rf into FAD. Mutations in FLAD1 gene are responsible for neuromuscular disorders, in some cases treatable with Rf. In order to mimic these disorders, the Caenorhabditis elegans (C. elegans) gene orthologue of FLAD1 (flad-1) was silenced in a model strain hypersensitive to RNA interference in nervous system. Silencing flad-1 resulted in a significant decrease in total flavin content, paralleled by a decrease in the level of the FAD-dependent ETFDH protein and by a secondary transcriptional down-regulation of the Rf transporter 1 (rft-1) possibly responsible for the total flavin content decrease. Conversely an increased ETFDH mRNA content was found. These biochemical changes were accompanied by significant phenotypical changes, including impairments of fertility and locomotion due to altered cholinergic transmission, as indicated by the increased sensitivity to aldicarb. A proposal is made that neuronal acetylcholine production/release is affected by alteration of Rf homeostasis. Rf supplementation restored flavin content, increased rft-1 transcript levels and eliminated locomotion defects. In this aspect, C. elegans could provide a low-cost animal model to elucidate the molecular rationale for Rf therapy in human Rf responsive neuromuscular disorders and to screen other molecules with therapeutic potential

Electrochemical synthesis of nanowire anodes from spent lithium ion batteries

A novel process is proposed to produce nanostructured batteries anodes from spent lithium-ion batteries. The electrodic powder recovered by the mechanical treatment of spent batteries was leached and the dissolved metals were precipitated as cobalt carbonates. Two different precipitation routes were separately tested producing cobalt carbonates with different Cu and Fe contents. Nanowire anodes were produced by electrodeposition into nanoporous alumina templates from the electrolytic baths prepared by dissolution of the precipitated carbonates. The electrochemical performances of the produced anodes were evaluated as compared to nanowire anodes produced with the same electrodeposition method but using a synthetic cobalt bath. The application of the carbonates produced by directly precipitating all the leached metals gave nanowires with capacity about halved as compared to the nanowires electrodeposited from the synthetic bath. Selectively removing Cu and Fe prior cobalt carbonate precipitation yielded, in contrast, nanowires with capacity initially larger and then gradually approaching that attained by the nanowire electrodeposited from the synthetic bath. A detailed analysis is presented describing the role of metallic impurities in determining the capacity of the produced nanowires. The impact of the illustrated results for the development of sustainable recycling processes of lithium-ion batteries is discussed

Improved Determination of the CKM Angle alpha from B to pi pi decays

Motivated by a recent paper that compares the results of the analysis of the CKM angle alpha in the frequentist and in the Bayesian approaches, we have reconsidered the information on the hadronic amplitudes, which helps constraining the value of alpha in the Standard Model. We find that the Bayesian method gives consistent results irrespective of the parametrisation of the hadronic amplitudes and that the results of the frequentist and Bayesian approaches are equivalent when comparing meaningful probability ranges or confidence levels. We also find that from B to pi pi decays alone the 95% probability region for alpha is the interval [80^o,170^o], well consistent with recent analyses of the unitarity triangle where, by using all the available experimental and theoretical information, one gets alpha = (93 +- 4)^o. Last but not least, by using simple arguments on the hadronic matrix elements, we show that the unphysical region alpha ~ 0, present in several experimental analyses, can be eliminated.Comment: 16 pages, 7 figure

Prevalence and predictors of subclinical atrial fibrillation in hospitalized older adults

Subclinical atrial fibrillation (SCAF) is associated with an increased risk of clinical AF, major cardiovascular events and death. Short-term evidence on SCAF in older populations is scarce, especially in the hospital setting. We performed a cross-sectional study on 60 multimorbid older consecutive patients (aged 80+) admitted to an Internal Medicine and Geriatrics Unit for acute medical diseases with no history of AF, in order to investigate prevalence and predictors of SCAF. Portable ECG monitoring was placed on admission and ECG recording lasted for 5 days. Mean age: 85.7±4.9 years. Female prevalence: 58.3%. High burden of comorbidities: 87.9%. All enrolled patients had CHA2 DS2-VASc score ≥3. SCAF was detected in 16 patients (26.7%) and 11 patients (18.4%) had at least a SCAF episode lasting 6 minutes or longer. No clinical, laboratory and echocardiographic parameters predicted SCAF. Patients with ≥2004 supraventricular ectopic beats/24h (SVEBs/24h) had a 6-fold higher prevalence of SCAF than patients with <411 SVEBs/24h (p=0.038). Time to first SCAF episode was within 3 days of ECG recording in all enrolled patients. SCAF is highly prevalent in older adults hospitalized for acute diseases. This finding may affect clinical management and prognosis. Our study could foster larger multicenter studies in similar settings