22 research outputs found

    Azithromycin resistance in Escherichia coli and Salmonella from food-producing animals and meat in Europe.

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    OBJECTIVES To characterize the genetic basis of azithromycin resistance in Escherichia coli and Salmonella collected within the EU harmonized antimicrobial resistance (AMR) surveillance programme in 2014-18 and the Danish AMR surveillance programme in 2016-19. METHODS WGS data of 1007 E. coli [165 azithromycin resistant (MIC > 16 mg/L)] and 269 Salmonella [29 azithromycin resistant (MIC > 16 mg/L)] were screened for acquired macrolide resistance genes and mutations in rplDV, 23S rRNA and acrB genes using ResFinder v4.0, AMRFinder Plus and custom scripts. Genotype-phenotype concordance was determined for all isolates. Transferability of mef(C)-mph(G)-carrying plasmids was assessed by conjugation experiments. RESULTS mph(A), mph(B), mef(B), erm(B) and mef(C)-mph(G) were detected in E. coli and Salmonella, whereas erm(C), erm(42), ere(A) and mph(E)-msr(E) were detected in E. coli only. The presence of macrolide resistance genes, alone or in combination, was concordant with the azithromycin-resistant phenotype in 69% of isolates. Distinct mph(A) operon structures were observed in azithromycin-susceptible (n = 50) and -resistant (n = 136) isolates. mef(C)-mph(G) were detected in porcine and bovine E. coli and in porcine Salmonella enterica serovar Derby and Salmonella enterica 1,4, [5],12:i:-, flanked downstream by ISCR2 or TnAs1 and associated with IncIγ and IncFII plasmids. CONCLUSIONS Diverse azithromycin resistance genes were detected in E. coli and Salmonella from food-producing animals and meat in Europe. Azithromycin resistance genes mef(C)-mph(G) and erm(42) appear to be emerging primarily in porcine E. coli isolates. The identification of distinct mph(A) operon structures in susceptible and resistant isolates increases the predictive power of WGS-based methods for in silico detection of azithromycin resistance in Enterobacterales

    Replication Fork Stability Confers Chemoresistance in BRCA-deficient Cells

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    Brca1- and Brca2-deficient cells have reduced capacity to repair DNA double-strand breaks (DSBs) by homologous recombination (HR) and consequently are hypersensitive to DNA damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3/4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore HR activity at DSBs. Instead, its absence inhibits the recruitment of the MRE11 nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARPi and cisplatin resistance is associated with replication fork (RF) protection in Brca2-deficient tumor cells that do not develop Brca2 reversion mutations. Disruption of multiple proteins, including PARP1 and CHD4, leads to the same end point of RF protection, highlighting the complexities by which tumor cells evade chemotherapeutic interventions and acquire drug resistance

    Spinal Vascular Shunts: Single-Center Series and Review of the Literature of Their Classification

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    Spinal arteriovenous shunts (sAVSs) are an uncommon disease, constituting 3 to 4% of intradural lesions; 70% of these lesions are spinal arteriovenous fistulas (sAVFs), whereas spinal arteriovenous malformations (sAVMs) are rarer. Both share the problem of their classification due to the heterogeneity of their angioarchitecture. The aim of this study is to report a series of sAVSs treated in the neurosurgery department of the Hospital Nacional Guillermo Almenara during the 2018-2020 period and to present an overview of the current literature on sAVS classification. We reviewed all medical records of patients diagnosed with sAVFs and sAVMs during the 2018-2020 period, and then we analyzed images with Horos v4.0.0, illustrated some cases with Clip Studio Paint v1.10.5, and performed a descriptive statistical analysis with SPSS v25. Twelve patients were included in this study, eight of which were women (67%) and four of which were men (33%); the age range was from 3 to 74 years. Eight sAVSs were sAVFs, whereas four were sAVMs. The most frequent clinical manifestation was chronic myelopathy in seven patients (58%). Of those treated only by embolization, seven (70%) resulted in complete occlusion (five sAVFs and two sAVMs), while three (30%) remained with a residual lesion. At last follow-up, five patients (42%) improved clinically, and the seven remaining (58%) maintained the same neurological state. sAVSs require a detailed study of their angioarchitecture for proper management. The endovascular treatment is safe with acceptable cure rates. The surgical option should not be set aside

    New Targets and New Technologies in the Treatment of Parkinson’s Disease: A Narrative Review

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    Parkinson's disease (PD) is a progressive neurodegenerative disease, whose main neuropathological finding is pars compacta degeneration due to the accumulation of Lewy bodies and Lewy neurites, and subsequent dopamine depletion. This leads to an increase in the activity of the subthalamic nucleus (STN) and the internal globus pallidus (GPi). Understanding functional anatomy is the key to understanding and developing new targets and new technologies that could potentially improve motor and non-motor symptoms in PD. Currently, the classical targets are insufficient to improve the entire wide spectrum of symptoms in PD (especially non-dopaminergic ones) and none are free of the side effects which are not only associated with the procedure, but with the targets themselves. The objective of this narrative review is to show new targets in DBS surgery as well as new technologies that are under study and have shown promising results to date. The aim is to give an overview of these new targets, as well as their limitations, and describe the current studies in this research field in order to review ongoing research that will probably become effective and routine treatments for PD in the near future

    pH and Anion Effects on Cu-Phosphate Interfaces for CO Electroreduction

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    Herein, we have investigated the interfacial properties of Cu(111) and Cu(100) in phosphate buffer solutions at different pH conditions and in presence of CO. Ab initio molecular simulations of the Cu-electrolyte interface were combined with voltammetric experiments carried out on Cu(100) and Cu(111) single-crystalline electrodes. We show that the adsorption strength of phosphate species on the different Cu facets affects the potential range at which CO poisons the surface. The properties of the Cu-electrolyte interface controls the potential range for CO reduction on Cu
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