A severe infective endocarditis successfully treated with linezolid

Despite significant improvements in surgical and medical therapy, prosthetic valve endocarditis (PVE) is a diagnostic and therapeutic challenge and is often associated with a severe prognosis. We report a case of a 59-year-old woman, with  PVE and bacterial endocarditis (Streptococcus bovis) successfully treated with linezolid. Linezolid is a bacteriostatic oxazolidinone antibiotic that has been proven to be effective for the treatment of patients with pneumonia, skin and soft tissue infections, and infections due to Gram-positive cocci. Linezolid is not yet recognised as a standard therapy for infective endocarditis, but its use becomes a necessity when infection is due to multidrug-resistant microorganisms

Breast cancer cells treated with proton beam: Immunological features and gene signatures

The breast cancer (BC) disease is characterized by a wide heterogeneity at both clinical and molecular level, showing distinct subtypes with different clinical outcomes. Thus, the choice of the therapeutic plan, such as the type of radiotherapy (RT) need to take into account this complexity. Indeed, the proton therapy (PT) shows a medical benefit compared to conventional X-ray RT, as regards the localized delivery of the radiation dose sparing health tissues, but few data regarding proton-induced molecular changes are currently available. The aim of this study was therefore to investigate the production of immunological molecules and gene expression profiles induced by proton irradiation on BC cell lines. Clonogenic survival assay, luminex assay and cDNA microarray gene expression analyses were performed both in the non-tumorigenic MCF10A cell line and in two tumorigenic MCF7 and MDA-MB-231 cell lines, following irradiation with 0.5, 2 and 9 Gy of clinical proton beams. We found that proton irradiation induced gene expression changes useful to define a cell line and dose-dependent gene signatures. The lack of molecular data in the literature can be filled by data here presented that could represent a useful tool to better understand the molecular mechanisms elicited by protons predicting the treatment outcome

Preliminary study of novel SRC tyrosine kinase inhibitor and proton therapy combined effect on glioblastoma multiforme cell line: In vitro evaluation of target therapy for the enhancement of protons effectiveness

The aim of this work was to evaluate proton therapy effectiveness in combination with a molecule SRC protein inhibitor for glioblastoma multiforme treatment. The role of this novel compound, Si306, is to interfere with glioblastoma carcinogenesis and progression, creating a radiosensitivity condition. The experiments were performed on U87 human glioblastoma multiforme cell line. Molecule concentrations of 10 μM and 20μM were tested in combination with proton irradiation doses of 2, 4, 10 and 21Gy. Cell survival evaluation was performed by clonogenic assay. The results showed that Si306 increases the efficacy of proton therapy reducing the surviving cells fraction significantly compared to treatment with protons only. These studies will support the preclinical phase realization, in order to evaluate proton therapy effects and molecularly targeted drug combined treatments

Proton-irradiated breast cells: molecular points of view

Breast cancer (BC) is the most common cancer in women, highly heterogeneous at both the clinical and molecular level. Radiation therapy (RT) represents an efficient modality to treat localized tumor in BC care, although the choice of a unique treatment plan for all BC patients, including RT, may not be the best option. Technological advances in RT are evolving with the use of charged particle beams (i.e. protons) which, due to a more localized delivery of the radiation dose, reduce the dose administered to the heart compared with conventional RT. However, few data regarding proton-induced molecular changes are currently available. The aim of this study was to investigate and describe the production of immunological molecules and gene expression profiles induced by proton irradiation. We performed Luminex assay and cDNA microarray analyses to study the biological processes activated following irradiation with proton beams, both in the non-tumorigenic MCF10A cell line and in two tumorigenic BC cell lines, MCF7 and MDA-MB-231. The immunological signatures were dose dependent in MCF10A and MCF7 cell lines, whereas MDA-MB-231 cells show a strong pro-inflammatory profile regardless of the dose delivered. Clonogenic assay revealed different surviving fractions according to the breast cell lines analyzed. We found the involvement of genes related to cell response to proton irradiation and reported specific cell line- and dose-dependent gene signatures, able to drive cell fate after radiation exposure. Our data could represent a useful tool to better understand the molecular mechanisms elicited by proton irradiation and to predict treatment outcome

Analysis of the role of elution buffers on the separation capabilities of dielectrophoretic devices

Field flow fractionation dielectrophoretic (FFF-DEP) devices are currently used, among the others, for the separation of tumor cells from healthy blood cells. To this end specific suspension/elution buffers (EBs), with reduced conductivity (with respect to that of the cell cytoplasm) are generally used. In this paper we investigate the long-term alterations of the cells and elution buffers. We find that the EB conductivity is critically modified within few minutes after cells suspension. In turn, this modification results in a change the ideal separation frequency of the FFF-DEP device. On the other hand we prove that DEP manipulation is preserved for more than three hours for cells suspended in the considered EBs. Keywords: Dielectrophoresis, Elution buffer, Circulating tumor cells, Cell motilit

Molecular Investigation on a Triple Negative Breast Cancer Xenograft Model Exposed to Proton Beams

Specific breast cancer (BC) subtypes are associated with bad prognoses due to the absence of successful treatment plans. The triple-negative breast cancer (TNBC) subtype, with estrogen (ER), progesterone (PR) and human epidermal growth factor-2 (HER2) negative receptor status, is a clinical challenge for oncologists, because of its aggressiveness and the absence of effective therapies. In addition, proton therapy (PT) represents an effective treatment against both inaccessible area located or conventional radiotherapy (RT)-resistant cancers, becoming a promising therapeutic choice for TNBC. Our study aimed to analyze the in vivo molecular response to PT and its efficacy in a MDA-MB-231 TNBC xenograft model. TNBC xenograft models were irradiated with 2, 6 and 9 Gy of PT. Gene expression profile (GEP) analyses and immunohistochemical assay (IHC) were performed to highlight specific pathways and key molecules involved in cell response to the radiation. GEP analysis revealed in depth the molecular response to PT, showing a considerable immune response, cell cycle and stem cell process regulation. Only the dose of 9 Gy shifted the balance toward pro-death signaling as a dose escalation which can be easily performed using proton beams, which permit targeting tumors while avoiding damage to the surrounding healthy tissue

List of non-EU viruses and viroids of Cydonia Mill., Fragaria L., Malus Mill., Prunus L., Pyrus L., Ribes L., Rubus L. and Vitis L.

The Panel on Plant Health performed a listing of non-EU viruses and viroids (reported hereinafter as viruses) of Cydonia Mill., Fragaria L., Malus Mill., Prunus L., Pyrus L., Ribes L., Rubus L. and Vitis L. A systematic literature review identified 197 viruses infecting one or more of the host genera under consideration. Viruses were allocated into three categories (i) 86 non-EU viruses, known to occur only outside the EU or having only limited presence in the EU (i.e. reported in only one or few Member States (MSs), known to have restricted distribution, outbreaks), (ii) 97 viruses excluded at this stage from further categorisation efforts because they have significant presence in the EU (i.e. only reported so far from the EU or known to occur or be widespread in some MSs or frequently reported in the EU), (iii) 14 viruses with undetermined standing for which available information did not readily allow to allocate to one or the other of the two above groups. Comments provided by MSs during consultation phases were integrated in the opinion. The main knowledge gaps and uncertainties of this listing concern (i) the geographic distribution and prevalence of the viruses analysed, in particular when they were recently described; (ii) the taxonomy and biological status of a number of poorly characterised viruses; (iii) the host status of particular plant genera in relation to some viruses. The viruses considered as non-EU and those with undetermined standing will be categorised in the next steps to answer a specific mandate from the Commission to develop pest categorisations for non-EU viruses. This list does not imply a prejudice on future needs for a pest categorisation for other viruses which are excluded from the current categorisation efforts

Pest categorisation of non-EU viruses of Ribes L

Following a request from the EU Commission, the Panel on Plant Health addressed the pest categorisation of the viruses of Ribes L. determined as being either non-EU or of undetermined standing in a previous EFSA opinion. These infectious agents belong to different genera and are heterogeneous in their biology. Alaska vitivirus 1 and Ribes virus F were excluded from categorisation because these are very poorly characterised viruses. The pest categorisation was completed for seven viruses with clear identity and for which detection methods are available. All these viruses are efficiently transmitted by vegetative propagation techniques, with plants for planting representing the major pathway for longdistance dispersal and thus considered as the major pathway for entry. Depending on the virus, additional pathway(s) can also be Ribes seeds, pollen and/or vector(s). Most of the viruses categorised here are known to infect only one or few plant genera, but tomato ringspot virus (ToRSV) has a wide host range, thus extending the possible entry pathways. ToRSV meets all the criteria evaluated by EFSA to qualify as potential Union quarantine pest (QP). With the exception of impact in the EU territory, on which the Panel was unable to conclude, Actinidia virus X, blackcurrant leaf chlorosis-associated virus, blackcurrant leafroll-associated virus, black currant-associated rhabdovirus, blackcurrant waikavirus A and Ribes americanum virus A satisfy all the other criteria to be considered as potential Union QPs. For several viruses, especially those recently discovered, the categorisation is associated with high uncertainties mainly because of the absence of data on their biology, distribution and impact. Since this opinion addresses specifically the non-EU viruses, in general these viruses do not meet the criteria assessed by EFSA to qualify as potential Union regulated non-quarantine pests