Prevalence of resistance to colistin, tigecycline and minocycline in Acinetobacter baumannii isolated from clinical samples in 2014

Background: Colonization rate of Acinetobacter baumannii is increasing in hospitalized patients especially in long term hospitalized one and / or who were treat with extended spectrum antibiotics or anticancer. Antibiotic resistance in A. baumannii is considerable because more prevalence of them cause nosocomial infections and can impose high cost to health systems and patients. The aim of this study was determination of tigecycline, minocycline and colistin resistance A. baumannii in selected center in Tehran, Iran. Materials and Methods: This study was descriptive and functional foundation. In this study A. baumannii were collected from Milad, Mofid, Taleghani, Motahari and Loghman hospital, Tehran and transferred to laboratory of pediatric infections research center. Collected bacteria were identified by conventional microbiology tests. Antibiotic susceptibility testing was determined according to CLSI guide line. Tigecycline, minocycline and colistin resistance strains were isolated.  Results: In this study, 105 A. baumannii were collected from five selected hospitals: 48 (46%) from Milad, 33 (31%) from Motahari, 17 (16%) from Loghman, 4 (4%) from Mofid and 3 (3%) from Taleghani hospital. The highest resistance was observed against cefepime and high frequency of carbapenem and minocycline was observed. On the other hand, observed resistance to aminoglycosides was 93% at least. Tigecycline is the most effective antibiotic after colistin. Colistin resistant confirmed just in one isolate by E. test. Conclusion: The results of this study indicated that high rate of antibiotic resistance in A. baumannii even resistant to third and fourth generation of cephalosporin and carbapenem antibiotics. The treatment of MDR strains of A. baumannii become more complicated if the spread of them were not been controlled

A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma

The heterogeneity of cellular states in cancer has been linked to drug resistance, cancer progression and the presence of cancer cells with properties of normal tissue stem cells. Secreted Wnt signals maintain stem cells in various epithelial tissues, including in lung development and regeneration. Here we show that mouse and human lung adenocarcinomas display hierarchical features with two distinct subpopulations, one with high Wnt signalling activity and another forming a niche that provides the Wnt ligand. The Wnt responder cells showed increased tumour propagation ability, suggesting that these cells have features of normal tissue stem cells. Genetic perturbation of Wnt production or signalling suppressed tumour progression. Small-molecule inhibitors targeting essential posttranslational modification of Wnt reduced tumour growth and markedly decreased the proliferative potential of lung cancer cells, leading to improved survival of tumour-bearing mice. These results indicate that strategies for disrupting pathways that maintain stem-like and niche cell phenotypes can translate into effective anti-cancer therapies

Evaluation of Clarithromycin and Metronidazole Resistance of Helicobacter Pylori Infection in Symptomatic Iranian Children

Helicobacter Pylori (H. pylori) as a gram-negative bacterium is the most common infection of the gastrointestinal tract, and worldwide it affects the children over three years of age. H. pylori could cause gastrointestinal and extra-intestinal manifestations. Antibiotic resistance can happen primarily and occurs during treatment. We aimed to evaluate the resistance gene of H. pylori obtained from gastric biopsy by polymerase chain reaction (PCR) method in Iranian children over 3 years old. Materials and Methods This study was a cross-sectional to evaluate the resistance gene of H. pylori obtained from gastric biopsy by polymerase chain reaction method for metronidazole and clarithromycin in children over three years old referring to the Mofid Children's Medical Center in Tehran, Iran. Results: Finally, data from seventy-nine samples included (mean age=10.7 years and male gender = 60.8%). Beta Globulin (BG) gene were detectable in 75 (94.93%) specimens of 79 (100%). Seventeen out of 75 specimens showed positive results for molecular detection of H. pylori. The results of RFLP-PCR technique showed that mutation of RdxA gene in seven of 17 (41.1%) for Metronidazole resistance and one case of 17 (5.8%) mutation of 23Y RNA gene that leads to clarithromycin resistance. Conclusion: Regarding the results of our study, it is better to check microbial resistance by culture and antibiogram for the antibiotic regimen of the first and second line of H. pylori treatment in children

Eptifibatide-induced profound thrombocytopaenia: a rare complication.

Drug-induced immune thrombocytopaenia (DITP) is a type of thrombocytopaenia caused by medications. It is one of the common causes of unexplained thrombocytopaenia. It is caused by the formation of autoantibodies against a particular drug and is commonly observed with medications like heparin and beta-lactam antibiotics. One of the rare causes of DITP is eptifibatide, a widely used antiplatelet agent for pretreatment in cardiac catheterisation. These patients can be asymptomatic or develop complications like skin bruising, epistaxis and even intracranial haemorrhage. We present a case of a 64-year-old man who developed eptifibatide-induced profound thrombocytopaenia leading to extensive skin bruising. He was treated with platelet transfusions followed by prompt improvement in platelet count

Symphony of the Surplus/Value : Notes on labour, valorization and sabotage in the metropolitan factory

This essay is a reflection on how art produces value using the work of Arseny Avraamov, Heath Bunting, and debates around cultural labour. It argues that art produces value not through exchange itself or through labour as traditionally understood, but in how it renders value out of the labours of circulating ideas, images, and affects. Drawing from this perspective, and informed by autonomist theories of class composition, it then considers possibilities for the sabotage of value within circuits of artistic value production, such as in the regeneration of cities through an arts based economy. © 2012 Taylor and Francis Group, LLC

In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis.

In vivo interrogation of the function of genes implicated in tumorigenesis is limited by the need to generate and cross germline mutant mice. Here we describe approaches to model colorectal cancer (CRC) and metastasis, which rely on in situ gene editing and orthotopic organoid transplantation in mice without cancer-predisposing mutations. Autochthonous tumor formation is induced by CRISPR-Cas9-based editing of the Apc and Trp53 tumor suppressor genes in colon epithelial cells and by orthotopic transplantation of Apc-edited colon organoids. ApcΔ/Δ;Kras(G12D/+);Trp53Δ/Δ (AKP) mouse colon organoids and human CRC organoids engraft in the distal colon and metastasize to the liver. Finally, we apply the orthotopic transplantation model to characterize the clonal dynamics of Lgr5(+) stem cells and demonstrate sequential activation of an oncogene in established colon adenomas. These experimental systems enable rapid in vivo characterization of cancer-associated genes and reproduce the entire spectrum of tumor progression and metastasis.</p

Genomic and Functional Fidelity of Small Cell Lung Cancer Patient-Derived Xenografts

Small cell lung cancer (SCLC) patient-derived xenografts (PDX) can be generated from biopsies or circulating tumor cells (CTC), though scarcity of tissue and low efficiency of tumor growth have previously limited these approaches. Applying an established clinical-translational pipeline for tissue collection and an automated microfluidic platform for CTC enrichment, we generated 17 biopsy-derived PDXs and 17 CTC-derived PDXs in a 2-year timeframe, at 89% and 38% efficiency, respectively. Whole-exome sequencing showed that somatic alterations are stably maintained between patient tumors and PDXs. Early-passage PDXs maintain the genomic and transcriptional profiles of the founder PDX. In vivo treatment with etoposide and platinum (EP) in 30 PDX models demonstrated greater sensitivity in PDXs from EP-naive patients, and resistance to EP corresponded to increased expression of a MYC gene signature. Finally, serial CTC-derived PDXs generated from an individual patient at multiple time points accurately recapitulated the evolving drug sensitivities of that patient's disease. Collectively, this work highlights the translational potential of this strategy. SIGNIFICANCE: Effective translational research utilizing SCLC PDX models requires both efficient generation of models from patients and fidelity of those models in representing patient tumor characteristics. We present approaches for efficient generation of PDXs from both biopsies and CTCs, and demonstrate that these models capture the mutational landscape and functional features of the donor tumors. (C) 2018 AACR

STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS-Mutant Lung Adenocarcinoma.

KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) comutations define distinct subgroups of KRAS-mutant LUAC. Here, we examine the efficacy of PD-1 inhibitors in these subgroups. Objective response rates to PD-1 blockade differed significantly among KL (7.4%), KP (35.7%), and K-only (28.6%) subgroups (P &lt; 0.001) in the Stand Up To Cancer (SU2C) cohort (174 patients) with KRAS-mutant LUAC and in patients treated with nivolumab in the CheckMate-057 phase III trial (0% vs. 57.1% vs. 18.2%; P = 0.047). In the SU2C cohort, KL LUAC exhibited shorter progression-free (P &lt; 0.001) and overall (P = 0.0015) survival compared with KRASMUT;STK11/LKB1WT LUAC. Among 924 LUACs, STK11/LKB1 alterations were the only marker significantly associated with PD-L1 negativity in TMBIntermediate/High LUAC. The impact of STK11/LKB1 alterations on clinical outcomes with PD-1/PD-L1 inhibitors extended to PD-L1-positive non-small cell lung cancer. In Kras-mutant murine LUAC models, Stk11/Lkb1 loss promoted PD-1/PD-L1 inhibitor resistance, suggesting a causal role. Our results identify STK11/LKB1 alterations as a major driver of primary resistance to PD-1 blockade in KRAS-mutant LUAC.Significance: This work identifies STK11/LKB1 alterations as the most prevalent genomic driver of primary resistance to PD-1 axis inhibitors in KRAS-mutant lung adenocarcinoma. Genomic profiling may enhance the predictive utility of PD-L1 expression and tumor mutation burden and facilitate establishment of personalized combination immunotherapy approaches for genomically defined LUAC subsets. Cancer Discov; 8(7); 822-35. ©2018 AACR.See related commentary by Etxeberria et al., p. 794This article is highlighted in the In This Issue feature, p. 781