The relevance of BRAF G469A mutation in determining the response to therapy in metastatic melanoma

N.A

Trend of sexually transmitted infections during the Covid-19 age. What was the impact of the pandemic and the social distancing measures?

Covid-19 pandemic has led to social distancing guidelines andresource allocation with subsequent impairment of sexual healthservices. The impact of such measures and the recommendationsregarding changes of sexual behaviour is a matter of debate

First results of a novel Silicon Drift Detector array designed for low energy X-ray fluorescence spectroscopy

We developed a trapezoidal shaped matrix with 8 cells of Silicon Drift Detectors (SDD) featuring a very low leakage current (below 180 pA/cm2 at 20 \ub0C) and a shallow uniformly implanted p+ entrance window that enables sensitivity down to few hundreds of eV. The matrix consists of a completely depleted volume of silicon wafer subdivided into 4 square cells and 4 half-size triangular cells. The energy resolution of a single square cell, readout by the ultra-low noise SIRIO charge sensitive preamplifier, is 158 eV FWHM at 5.9 keV and 0 \ub0C. The total sensitive area of the matrix is 231 mm2 and the wafer thickness is 450\u3bcm. The detector was developed in the frame of the INFN R&D project ReDSoX in collaboration with FBK, Trento. Its trapezoidal shape was chosen in order to optimize the detection geometry for the experimental requirements of low energy X-ray fluorescence (LEXRF) spectroscopy, aiming at achieving a large detection angle. We plan to exploit the complete detector at the TwinMic spectromicroscopy beamline at the Elettra Synchrotron (Trieste, Italy). The complete system, composed of 4 matrices, increases the solid angle coverage of the isotropic photoemission hemisphere about 4 times over the present detector configuration. We report on the layout of the SDD matrix and of the experimental set-up, as well as the spectroscopic performance measured both in the laboratory and at the experimental beamline. \ua9 2015 Elsevier B.V

PLoS Pathog

The treatment of schistosomiasis, a disease caused by blood flukes parasites of the Schistosoma genus, depends on the intensive use of a single drug, praziquantel, which increases the likelihood of the development of drug-resistant parasite strains and renders the search for new drugs a strategic priority. Currently, inhibitors of human epigenetic enzymes are actively investigated as novel anti-cancer drugs and have the potential to be used as new anti-parasitic agents. Here, we report that Schistosoma mansoni histone deacetylase 8 (smHDAC8), the most expressed class I HDAC isotype in this organism, is a functional acetyl-L-lysine deacetylase that plays an important role in parasite infectivity. The crystal structure of smHDAC8 shows that this enzyme adopts a canonical alpha/beta HDAC fold, with specific solvent exposed loops corresponding to insertions in the schistosome HDAC8 sequence. Importantly, structures of smHDAC8 in complex with generic HDAC inhibitors revealed specific structural changes in the smHDAC8 active site that cannot be accommodated by human HDACs. Using a structure-based approach, we identified several small-molecule inhibitors that build on these specificities. These molecules exhibit an inhibitory effect on smHDAC8 but show reduced affinity for human HDACs. Crucially, we show that a newly identified smHDAC8 inhibitor has the capacity to induce apoptosis and mortality in schistosomes. Taken together, our biological and structural findings define the framework for the rational design of small-molecule inhibitors specifically interfering with schistosome epigenetic mechanisms, and further support an anti-parasitic epigenome targeting strategy to treat neglected diseases caused by eukaryotic pathogens

Recurrent neurosurgical site infection by extensively drug-resistant P. aeruginosa treated with cefiderocol: a case report and literature review

Introduction: Cefiderocol is a new siderophore cephalosporin designed to be active against extensively resistant Gram-negative bacteria; however, clinical studies are limited to complicated urinary tract infections, pneumonia, and intra-abdominal infections. To date, no data are available on neurosurgical site infections. Case presentation: We present a case of a patient successfully cured with Cefiderocol for a neurosurgical site infection due to extensively resistant P. aeruginosa, who had failed a previous treatment based on combined antimicrobial therapy and right parietal bone excision. Conclusions: Cefiderocol is a promising antibiotic for complicated infections due to multidrug resistant gram-negative bacteria

Synthesis and biological evaluation of N-biphenyl-nicotinic based moiety compounds: A new class of antimitotic agents for the treatment of Hodgkin Lymphoma

We previously demonstrated that some N-biphenylanilides caused cell-cycle arrest at G2/M transition in breast cancer cells. Among them we choose three derivatives, namely PTA34, PTA73 and RS35 for experimentation in solid tumor cell lines, classical Hodgkin Lymphoma (cHL) cell lines and bona fide normal cell lines. Almost all tumor cells were sensitive to compounds in the nanomolar range whereas, they were not cytotoxic to normal ones. Interestingly the compounds caused a strong G2/M phase arrest in cHL cell lines, thus, here we investigated whether they affected the integrity of microtubules in such cells. We found that they induced a long prometaphase arrest, followed by induction of apoptosis which involved mitochondria. PTA73 and RS35 induced the mitotic arrest through the fragmentation of microtubules which prevented the kinethocore-mitotic spindle interaction and the exit from mitosis. PTA34 is instead a tubulin-targeting agent because it inhibited the tubulin polymerization as vinblastine. As such, PTA34 maintained the Cyclin B1-CDK1 regulatory complex activated during the G2/M arrest while inducing the inactivation of Bcl-2 through phosphorylation in Ser70, the degradation of Mcl-1 and a strong activation of BIML and BIMS proapoptotic isoforms. In addition PTA34 exerted an antiangiogenic effect by suppressing microvascular formation