The Physiopathology of T- Cell Acute Lymphoblastic Leukemia: Focus on Molecular Aspects

T-cell acute lymphoblastic leukemia/lymphoma is an aggressive hematological neoplasm whose classification is still based on immunophenotypic findings. Frontline treatment encompass high intensity combination chemotherapy with good overall survival; however, relapsing/refractory patients have very limited options. In the last years, the understanding of molecular physiopathology of this disease, lead to the identification of a subset of patients with peculiar genetic profile, namely \u201cearly T-cell precursors\u201d lymphoblastic leukemia, characterized by dismal outcome and indication to frontline allogeneic bone marrow transplant. In general, the most common mutations occur in the NOTCH1/FBXW7 pathway (60% of adult patients), with a positive prognostic impact. Other pathogenic steps encompass transcriptional deregulation of oncogenes/oncosuppressors, cell cycle deregulation, kinase signaling (including IL7R-JAK-STAT pathway, PI3K/AKT/mTOR pathway, RAS/MAPK signaling pathway, ABL1 signaling pathway), epigenetic deregulation, ribosomal dysfunction, and altered expression of oncogenic miRNAs or long non-coding RNA. The insight in the genomic landscape of the disease paves the way to the use of novel targeted drugs that might improve the outcome, particularly in relapse/refractory patients. In this review, we analyse available literature on T-ALL pathogenesis, focusing on molecular aspects of clinical, prognostic, and therapeutic significance

Assessment of the Biocompatibility of the PLLA-PLCL Scaffold Obtained by Electrospinning

AbstractElectrospun membranes of poly (L-Lactide) / poly (L-lactide-co-caprolactone) blend were produced and evaluated by physical and mechanical tests to use as a scaffold for cell growth. The membranes were seeded with endothelial cells (HUVEC) and after culturing time it was visualized by confocal laser scanning microscopy and scanning electron microscopy. The results indicate that the process parameters were capable of producing PLLA-PLCL membranes presenting fibers with diameters in the nanometer range. The scaffolds supported cell attachment and growth, indicating the feasibility of producing scaffolds by electrospinning technique, which could be used in tissue engineering applications

The role of Epstein-Barr virus in adults with bronchiectasis : A prospective cohort study

Epstein-Barr virus (EBV) is implicated in the progression of chronic obstructive pulmonary disease. We aimed to determine whether EBV correlates with bronchiectasis severity, exacerbations, and progression. We collected induced sputum in healthy controls and spontaneous sputum at 3-6-month intervals and onset of exacerbations in bronchiectasis patients between March 2017 and October 2018. EBV DNA was detected with quantitative polymerase chain reaction. We collected 442 sputum samples from 108 bronchiectasis patients and 50 induced sputum samples from 50 healthy controls. When stable, bronchiectasis patients yielded higher detection rates of EBV DNA (48.1% vs 20.0%; P =.001), but not viral loads (mean log load, 4.45 vs 4.76; P =.266), compared with controls; 64.9% of patients yielded consistent detection status between 2 consecutive stable visits. Neither detection rate (40.8% vs 48.1%; P =.393) nor load (mean log load, 4.34 vs 4.45; P =.580) differed between the onset of exacerbations and stable visits, nor between exacerbations and convalescence. Neither detection status nor viral loads correlated with bronchiectasis severity. EBV loads correlated negatively with sputum interleukin-1β (P =.002), CXC motif chemokine-8 (P =.008), and tumor necrosis factor-α levels (P =.005). Patients initially detected with, or repeatedly detected with, EBV DNA had significantly faster lung function decline and shorter time to next exacerbations (both P .05). The EBV strains detected in bronchiectasis patients were phylogenetically homologous. Patients with detection of EBV DNA have a shorter time to bronchiectasis exacerbations. EBV may contribute to bronchiectasis progression

Implant of Port-o-Cath for antineoplastic chemotherapy in a canine: case report

O Port-o-Cath é um cateter venoso central totalmente implantável, o qual permite a infusão de quimioterápicos, hemoderivados, nutrição parenteral e coleta de sangue. Este trabalho relata o caso de um canino com um tumor no membro pélvico que foi tratado cirurgicamente e recebeu o cateter para a quimioterapia antineoplásica. A paciente possuía um sarcoma sinovial, tumor incomum em cães, que acomete normalmente as articulações e exige terapia multimodal. O tratamento foi feito em duas etapas; na primeira, o membro foi amputado e, na segunda, foi realizado o implante do Port-o-Cath e exérese de nódulo metastático. A cadela respondeu satisfatoriamente à cirurgia e realizou as sessões de quimioterapia com perfeito funcionamento do cateter, indo a óbito por outras causas 90 dias após o procedimento. O implante de Port-o-Cath para a quimioterapia é um grande aliado à terapia multimodal preconizada para o câncer, podendo o cateter ser considerado em pacientes que necessitem de medicação quimioterápica por longo período.The Port-a-Cath is a totally implantable central venous catheter that allows the infusion of chemotherapeutic agents, blood products, parenteral nutrition, and blood sample collection. This work reports the case of a dog with a tumor in the pelvic limb that was treated surgically and received the catheter for cancer chemotherapy. The patient was diagnosed with synovial sarcoma, an uncommon tumor in dogs that usually affects the joints and requires multimodal therapy. The treatment was done in two steps, in the first the limb was amputated and in the second the Port-a-Cath implantation and the excision of the metastatic nodule were performed. The dog responded well to surgery and chemotherapy sessions held with proper functioning of the catheter, and died from other causes 90 days after the procedure. The implantation of Port-a-Cath for chemotherapy is a great ally of multimodal therapy recommended for cancer, so this catheter may be considered for patients requiring chemotherapy medication for a long period

Low temperature transport in AC-driven Quantum Dots in the Kondo regime

We present a fully nonequilibrium calculation of the low temperature transport properties of a quantum dot in the Kondo regime when an AC potential is applied to the gate voltage. We solve a time dependent Anderson model with finite on-site Coulomb interaction. The interaction self-energy is calculated up to second order in perturbation theory in the on-site interaction, in the context of the Keldysh non-equilibrium technique, and the effect of the AC voltage is taken into account exactly for all ranges of AC frequencies and AC intensities. The obtained linear conductance and time-averaged density of states of the quantum dot evolve in a non trivial way as a function of the AC frequency and AC intensity of the harmonic modulation.Comment: 30 pages,7 figure

Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths

We review observations of several classes of neutron-star-powered outflows: pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe interacting directly with interstellar medium (ISM), and magnetar-powered outflows. We describe radio, X-ray, and gamma-ray observations of PWNe, focusing first on integrated spectral-energy distributions (SEDs) and global spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering array of morphologies, with jets, trails, and other structures. Several of the 23 so far identified magnetars show evidence for continuous or sporadic emission of material, sometimes associated with giant flares, and a few possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02