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Σάββατο 29 Ιουλίου 2017

Celiac Disease

Celiac disease is a health condition of the small intestine in which you cannot eat gluten. When a person with celiac disease eats gluten, the immune system, which is supposed to help protect the body against disease, reacts by harming the cells of the lining of the small intestine and also may harm other parts of the body, such as the skin, bones, or brain (nervous system). Both dietary and genetic factors cause the disease.

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Tissue kallikrein-related peptidase 4 (KLK4), a novel biomarker in triple-negative breast cancer

Journal Name: Biological Chemistry
Issue: Ahead of print


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Catalase, a remarkable enzyme: targeting the oldest antioxidant enzyme to find a new cancer treatment approach

Journal Name: Biological Chemistry
Issue: Ahead of print


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Candidate Gene Identification of Feed Efficiency and Coat Color Traits in a C57BL/6J × Kunming F2 Mice Population Using Genome-Wide Association Study

Feed efficiency (FE) is a very important trait in livestock industry. Identification of the candidate genes could be of benefit for the improvement of FE trait. Mouse is used as the model for many studies in mammals. In this study, the candidate genes related to FE and coat color were identified using C57BL/6J (C57) × Kunming (KM) F2 mouse population. GWAS results showed that 61 and 2 SNPs were genome-wise suggestive significantly associated with feed conversion ratio (FCR) and feed intake (FI) traits, respectively. Moreover, the Erbin, Msrb2, Ptf1a, and Fgf10 were considered as the candidate genes of FE. The Lpl was considered as the candidate gene of FI. Further, the coat color trait was studied. KM mice are white and C57 ones are black. The GWAS results showed that the most significant SNP was located at chromosome 7, and the closely linked gene was Tyr. Therefore, our study offered useful target genes related to FE in mice; these genes may play similar roles in FE of livestock. Also, we identified the major gene of coat color in mice, which would be useful for better understanding of natural mutation of the coat color in mice.

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Paracetamol in Patent Ductus Arteriosus Treatment: Efficacious and Safe?

In preterm infants, failure or delay in spontaneous closure of Ductus Arteriosus (DA), resulting in the condition of Patent Ductus Arteriosus (PDA), represents a significant issue. A prolonged situation of PDA can be associated with several short- and long-term complications. Despite years of researches and clinical experience on PDA management, unresolved questions about the treatment and heterogeneity of clinical practices in different centers still remain, in particular regarding timing and modality of intervention. Nowadays, the most reasonable strategy seems to be reserving the treatment only to hemodynamically significant PDA. The first-line therapy is medical, and ibuprofen, related to several side effects especially in terms of nephrotoxicity, is the drug of choice. Administration of oral or intravenous paracetamol (acetaminophen) recently gained attention, appearing effective as traditional nonsteroidal anti-inflammatory drugs (NSAIDs) in PDA closure, with lower toxicity. The results of the studies analyzed in this review mostly support paracetamol efficacy in ductal closure, with inconstant low and transient elevation of liver enzymes as reported side effect. However, more studies are needed to confirm if this therapy shows a real safety profile and to evaluate its long-term outcomes, before considering paracetamol as first-choice drug in PDA treatment.

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Prevalence and Clinical Characteristics of Itch in Vitiligo and Its Clinical Significance

Objective. Vitiligo usually presented as asymptomatic depigmented macules and patches. Little is known regarding itch in vitiligo. This study aimed to evaluate the prevalence and characteristics of itch in vitiligo patients. Patients and Methods. A cross-sectional study was conducted on vitiligo patients. Itch character and intensity were determined through questionnaires. Evaluation was also made by dermatologists to define vitiligo subtype, body surface area, Koebner phenomenon (KP), and so on. Data were assessed by computer software. Results were considered statistically significant if . Results. Among 402 patients, itch on vitiliginous lesion presented in 20.2%. Prevalence of itch was most common in focal vitiligo (29.4%), followed by segmental vitiligo (20.3%) and nonsegmental vitiligo (19.6%), respectively. Tingling sensation was the most common itch-related symptom (82.7%). The median itch intensity is 5 by 10-point visual analog scale. Daily activity and sleep disturbance were observed in 60.5% and 39.5% of patients who experience itch. Itch occurred approximately 3 days prior to the development of lesions in 48.1% of patients. Thirty-two patients (78.1%) with both itch and KP type IIb had active disease. Conclusions. Itch in vitiligo is not uncommon. The presence of itch with KP type IIb may warrant the active vitiligo.

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JAK2/STAT3 Pathway Was Associated with the Protective Effects of IL-22 On Aortic Dissection with Acute Lung Injury

Patients with aortic dissection (AD) may present acute lung injury (ALI) that may affect the prognosis. In this study, we aim to investigate the roles and mechanism of IL-22 in the pathogenesis of AD complicated with ALI. Six hundred and twenty-one AD patients were included, and the incidence of ALI and pulmonary CT findings were analyzed. Mouse ALI model was established through AngII, and then IL-22 injection and AG490 were given. The pathological changes, infiltration of inflammatory cells, and expression of STAT3 were determined. For the in vitro experiment, cultivated pulmonary microvascular endothelial cells (PMVECs) were treated by angiotensin II (AngII), followed by treating with IL-22 and/or AG490. The expression and migration of STAT3 was determined. Flow cytometry was carried out to evaluate the apoptosis. IL-22 contributed to the expression of STAT3 in lung tissues and attenuation of ALI. IL-22 obviously inhibited the apoptosis of PMVECs mediated by AngII and downregulated the expression and intranuclear transmission of STAT3. Such phenomenon was completely inhibited upon administration of AG490, an inhibitor of JAK2. Our data showed IL-22 contributed to the inhibition of PMVEC apoptosis mediated by AngII through activating the JAK2/STAT3 signaling pathway, which may attenuate the ALI induced by AngII.

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Auditory Dysfunction in Patients with Huntington’s Disease

Huntington's disease (HD) is an autosomal, dominant neurodegenerative disease, caused by the multiplication of a cytosine-adenine-guanine (CAG) trinucleotide (triplet). The main clinical features of HD are motor impairment, progressive cognitive deterioration and behavioral disorders (for detailed information see Bates et al., 2014).

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Disturbed Desmoglein-2 in the Intercalated Disc of Pediatric Patients with Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) leads to disturbed contraction and force transduction, and is associated with substantial mortality in all age groups. Involvement of a disrupted composition of the intercalated disc (ID) has been reported. However, in children, little is established about such subcellular changes during disease, because of the pathological mix-up with the ongoing cardiac maturation. This leaves maladaptive remodeling often undetected. We aimed at illustrating subcellular alterations in children diagnosed with DCM compared to age-matched controls, focusing on ID proteins known to be crucially stable under healthy conditions and destabilized during cardiac injury in adults.

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A prospective study of serial imaging comparing FDG-PET and FLT PET during radical chemo-radiation for Non-Small Cell Lung Cancer: reduction of detectable proliferation associated with worse survival

Sixty Non-Small Cell Lung Cancer (NSCLC) patients, prescribed curative intent chemo-radiation therapy, were prospectively studied. 18F-FDG and 18F-FLT-PET/CT scans were acquired at baseline, week two and week four to monitor tumor cell metabolism and proliferation, respectively. Stable uptake of 18F-FLT at week two was associated with superior overall survival compared to patients whose tumors demonstrated reduced or absent 18F-FLT uptake. This suggests that suppression of tumor cell proliferation may weaken the tumoricidal effect of chemoradiation.

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PRADO: a palliative care model for every radiation oncology practice



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An Update of a Prospective Study of SBRT for Post-chemoradiation Residual Disease in Stage II/III Non-small Cell Lung Cancer

Chemoradiation (CRT) remains the standard of care for Stage III NSCLC although local recurrences are a significant problem. Dose escalation of radiation has met with mixed results. Given the success and safety of SBRT in early stage NSCLC, this manuscript describes the long term safety and results of adding an SBRT boost to CRT in an effort to escalate the dose of RT to the primary mass in patients with Stage II-III NSCLC.

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Effects of Higher Quality of Care on Initiation of Long-term Dialysis in Patients With CKD and Diabetes

The burden of diabetes-related chronic kidney disease (CKD) on individuals and society is increasing, shifting attention toward improving the quality of care for patients with CKD and diabetes. We assessed the quality of CKD care and its association with long-term dialysis, acute kidney injury (AKI), and death.

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Patients’ Experiences After CKD Diagnosis: A Meta-ethnographic Study and Systematic Review

Chronic kidney disease (CKD) is often asymptomatic at first diagnosis, and awareness of CKD is low in the general population. Thus, individuals who are unexpectedly identified as having CKD may struggle to adjust to living with this diagnosis. This study aims to synthesize qualitative research exploring patients' views and experiences of a CKD diagnosis and how they adjust to it.

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Authentication of collagen VI antibodies

Collagen VI is a ubiquitously-expressed macromolecule that forms unique microfibrillar assemblies in the extracellular matrix. Mutations in the COL6A1, COL6A2 and COL6A3 genes result in congenital muscular dystro...

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Four-color Fluorescence Immunohistochemistry of T-cell Subpopulations in Archival Formalin-fixed, Paraffin-embedded Human Oropharyngeal Squamous Cell Carcinoma Samples

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Multiparameter fluorescence immunohistochemistry can be used to assess the number, relative distribution, and localization of immune cell populations in the tumor microenvironment. This manuscript describes the use of this technique to analyze T-cell subpopulations in oropharyngeal cancer.

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Surgical Procedures and Methodology for a Preclinical Murine Model of De Novo Mammary Cancer Metastasis

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Pre-clinical models evaluating adjuvant therapy targeting breast cancer metastasis are lacking. To address this, we developed a murine model of de novo pulmonary mammary adenocarcinoma metastasis, wherein therapies administered in the adjuvant setting (post surgical resection of primary tumors) can be evaluated for efficacy in impacting previously seeded pulmonary metastases.

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Wasting Away: How to Treat Cachexia and Muscle Wasting in Chronic Disease?



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Computational and experimental assessment of influences of hemodynamic shear stress on carotid plaque

Studies have identified hemodynamic shear stress as an important determinant of endothelial function and atherosclerosis. In this study, we assess the influences of hemodynamic shear stress on carotid plaques.

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Muscle satellite cells are functionally impaired in myasthenia gravis: consequences on muscle regeneration

Abstract

Myasthenia gravis (MG) is a neuromuscular disease caused in most cases by anti-acetyl-choline receptor (AChR) autoantibodies that impair neuromuscular signal transmission and affect skeletal muscle homeostasis. Myogenesis is carried out by muscle stem cells called satellite cells (SCs). However, myogenesis in MG had never been explored. The aim of this study was to characterise the functional properties of myasthenic SCs as well as their abilities in muscle regeneration. SCs were isolated from muscle biopsies of MG patients and age-matched controls. We first showed that the number of Pax7+ SCs was increased in muscle sections from MG and its experimental autoimmune myasthenia gravis (EAMG) mouse model. Myoblasts isolated from MG muscles proliferate and differentiate more actively than myoblasts from control muscles. MyoD and MyoG were expressed at a higher level in MG myoblasts as well as in MG muscle biopsies compared to controls. We found that treatment of control myoblasts with MG sera or monoclonal anti-AChR antibodies increased the differentiation and MyoG mRNA expression compared to control sera. To investigate the functional ability of SCs from MG muscle to regenerate, we induced muscle regeneration using acute cardiotoxin injury in the EAMG mouse model. We observed a delay in maturation evidenced by a decrease in fibre size and MyoG mRNA expression as well as an increase in fibre number and embryonic myosin heavy-chain mRNA expression. These findings demonstrate for the first time the altered function of SCs from MG compared to control muscles. These alterations could be due to the anti-AChR antibodies via the modulation of myogenic markers resulting in muscle regeneration impairment. In conclusion, the autoimmune attack in MG appears to have unsuspected pathogenic effects on SCs and muscle regeneration, with potential consequences on myogenic signalling pathways, and subsequently on clinical outcome, especially in the case of muscle stress.



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Cytological features of the Warthin-like variant of salivary mucoepidermoid carcinoma

Abstract

Warthin-like mucoepidermoid carcinoma is a recently proposed variant of musoepidermoid carcinoma. Histologically, it is characterized by its close resemblance to Warthin tumor, including dense lymphocytic infiltration, flattened intermediate epithelium resembling squamous metaplasia, and cystic change. Given its histologic similarity to Warthin tumor, confirmatory testing for MAML2 rearrangement is often required for this diagnosis. Here we present the first cytologic reports of two 53-year-old female patients with parotid masses. In both cases, the fine needle aspirations showed fragments of bland epithelium with a squamous appearance, mucinous cyst content, and focal lymphocytic background. Neither frank keratinization nor mucinous cells were identified in the smears. Fluorescence in situ hybridization (FISH) study confirmed MAML2 rearrangement on the resection specimens in both. Other cytologic differential diagnoses, including Warthin tumor with metaplasia, lymphadenoma, and lymphoepithelial cyst, were briefly discussed.



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Table of Contents

Publication date: August 2017
Source:The Spine Journal, Volume 17, Issue 8





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Table of Contents

Publication date: August 2017
Source:The Spine Journal, Volume 17, Issue 8





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Meetings Calendar

Publication date: August 2017
Source:The Spine Journal, Volume 17, Issue 8





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Table of Contents

Publication date: August 2017
Source:The Spine Journal, Volume 17, Issue 8





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Table of Contents

Publication date: August 2017
Source:The Spine Journal, Volume 17, Issue 8





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Editorial Board

Publication date: August 2017
Source:The Spine Journal, Volume 17, Issue 8





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Reliability of smartphone-based teleradiology for evaluating thoracolumbar spine fractures: statistical issue to avoid misinterpretation

Publication date: August 2017
Source:The Spine Journal, Volume 17, Issue 8
Author(s): Siamak Sabour




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Reply to letter to the editor titled “Reliability of smartphone-based teleradiology for evaluating thoracolumbar spine fractures: statistical issue to avoid misinterpretation”

Publication date: August 2017
Source:The Spine Journal, Volume 17, Issue 8
Author(s): Ido Stahl, Elias Haddad, Nir Hous, Daniel Dreyfuss




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High- and low-Molecular Weight oat Beta-Glucan Reveals Antitumor Activity in Human Epithelial Lung Cancer

Abstract

Beta-glucans are widely used in treatment, cosmetics, and the food industry. Glucans play a significant role in activation of the immune and antioxidant system and inhibiting tumor proliferation. In the current study the antitumor activities of new high and low molecular weight beta-glucan derived from oats were investigated in two human lung cancer cell line (A549, H69AR) and normal keratinocytes (HaCaT). The effect of high and low molecular weight beta-glucan from oat was evaluated by cellular viability assessment, lipid peroxidation and manganese superoxide dismutase evaluation and cytoskeleton visualisation. Additionally the level of red blood cells hemolysis was performed. Our results indicate strong anti-tumor properties of new beta-glucan from oat and at the same time no toxicity for normal cells.



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Primary Mucin Secreting Adenocarcinoma Bladder: a Case Series

Abstract

Primary mucinous adenocarcinoma is an extremely rare type of bladder cancer. These tumours may have varied presenting complains with isolated mucusuria in some patients. As it is difficult to differentiate primary from secondary tumours, it is often a diagnostic dilemma. We narrate three cases of primary mucinous adenocarcinoma bladder and try to bring out the clinical and pathological features unique to this tumour along with the diagnostic importance of immunohistochemistry.



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Knockout of MARCH2 inhibits the growth of HCT116 colon cancer cells by inducing endoplasmic reticulum stress

Knockout of MARCH2 inhibits the growth of HCT116 colon cancer cells by inducing endoplasmic reticulum stress

Cell Death and Disease 8, e2957 (July 2017). doi:10.1038/cddis.2017.347

Authors: Dan Xia, Wanli Ji, Chentong Xu, Xin Lin, Xiaokun Wang, Yan Xia, Ping Lv, Quansheng Song, Dalong Ma & Yingyu Chen



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Retinoic acid-induced upregulation of miR-219 promotes the differentiation of embryonic stem cells into neural cells

Retinoic acid-induced upregulation of miR-219 promotes the differentiation of embryonic stem cells into neural cells

Cell Death and Disease 8, e2953 (July 2017). doi:10.1038/cddis.2017.336

Authors: Haibo Wu, Jiamin Zhao, Beibei Fu, Songna Yin, Chao Song, Jingcheng Zhang, Shanting Zhao & Yong Zhang



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Cancer cell resistance to anoikis: MUC1 glycosylation comes to play

Cancer cell resistance to anoikis: MUC1 glycosylation comes to play

Cell Death and Disease 8, e2962 (July 2017). doi:10.1038/cddis.2017.363

Author: Lu-Gang Yu



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WWOX sensitises ovarian cancer cells to paclitaxel via modulation of the ER stress response

WWOX sensitises ovarian cancer cells to paclitaxel via modulation of the ER stress response

Cell Death and Disease 8, e2955 (July 2017). doi:10.1038/cddis.2017.346

Authors: Szymon Janczar, Jaya Nautiyal, Yi Xiao, Edward Curry, Mingjun Sun, Elisa Zanini, Adam JW Paige & Hani Gabra



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Keratin 23 promotes telomerase reverse transcriptase expression and human colorectal cancer growth

Keratin 23 promotes telomerase reverse transcriptase expression and human colorectal cancer growth

Cell Death and Disease 8, e2961 (July 2017). doi:10.1038/cddis.2017.339

Authors: Ningning Zhang, Rui Zhang, Kun Zou, Wendan Yu, Wei Guo, Yingying Gao, Jia Li, Mei Li, Yidi Tai, Wenlin Huang, Chun Song, Wuguo Deng & Xiaonan Cui



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miR-181d and c-myc-mediated inhibition of CRY2 and FBXL3 reprograms metabolism in colorectal cancer

miR-181d and c-myc-mediated inhibition of CRY2 and FBXL3 reprograms metabolism in colorectal cancer

Cell Death and Disease 8, e2958 (July 2017). doi:10.1038/cddis.2017.300

Authors: Xiaofeng Guo, Yuekun Zhu, Xinya Hong, Mukun Zhang, Xingfeng Qiu, Zhenfa Wang, Zhongquan Qi & Xuehui Hong



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Yet another hump for CAML: support of cell survival independent of tail-anchored protein insertion

Yet another hump for CAML: support of cell survival independent of tail-anchored protein insertion

Cell Death and Disease 8, e2960 (July 2017). doi:10.1038/cddis.2017.334

Authors: Jennifer C Shing & Richard J Bram



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The cohesin complex prevents Myc-induced replication stress

The cohesin complex prevents Myc-induced replication stress

Cell Death and Disease 8, e2956 (July 2017). doi:10.1038/cddis.2017.345

Authors: Sara Rohban, Aurora Cerutti, Marco J Morelli, Fabrizio d'Adda di Fagagna & Stefano Campaner



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Pre-synaptic TrkB in basolateral amygdala neurons mediates BDNF signaling transmission in memory extinction

Pre-synaptic TrkB in basolateral amygdala neurons mediates BDNF signaling transmission in memory extinction

Cell Death and Disease 8, e2959 (July 2017). doi:10.1038/cddis.2017.302

Authors: Yuan Li, Dongdong Wang, Yang Li, Hongxia Chu, Lining Zhang, Ming Hou, Xingyu Jiang, Zheyu Chen, Bo Su & Tao Sun



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Zinc oxide nanoparticles harness autophagy to induce cell death in lung epithelial cells

Zinc oxide nanoparticles harness autophagy to induce cell death in lung epithelial cells

Cell Death and Disease 8, e2954 (July 2017). doi:10.1038/cddis.2017.337

Authors: Jun Zhang, Xia Qin, Bin Wang, Ge Xu, Zhexue Qin, Jian Wang, Lanxiang Wu, Xiangwu Ju, Diptiman D Bose, Feng Qiu, Honghao Zhou & Zhen Zou



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DNMT1-maintained hypermethylation of Krüppel-like factor 5 involves in the progression of clear cell renal cell carcinoma

DNMT1-maintained hypermethylation of Krüppel-like factor 5 involves in the progression of clear cell renal cell carcinoma

Cell Death and Disease 8, e2952 (July 2017). doi:10.1038/cddis.2017.323

Authors: Rong-Jie Fu, Wei He, Xiao-Bo Wang, Lei Li, Huan-Bin Zhao, Xiao-Ye Liu, Zhi Pang, Guo-Qiang Chen, Lei Huang & Ke-Wen Zhao



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Acid sphingomyelinase mediates human CD4+ T-cell signaling: potential roles in T-cell responses and diseases

Acid sphingomyelinase mediates human CD4+ T-cell signaling: potential roles in T-cell responses and diseases

Cell Death and Disease 8, e2963 (July 2017). doi:10.1038/cddis.2017.360

Authors: Aiping Bai & Yuan Guo



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Intricatinol synergistically enhances the anticancerous activity of cisplatin in human A549 cells via p38 MAPK/p53 signalling

Abstract

Platinum containing drugs are widely used to treat advanced lung carcinomas. However, their clinical success is still limited due to severe side effects, and drug resistance. Alternative approaches are warranted to augment efficacy of platinum based chemotherapeutic drugs with minimal side effects. Intricatinol (INT), a homoisoflavonoid, has been shown to possess anti-tubercular, antioxidant, hypoglycaemic, and hypolipidemic activity. However, its anticancer activity largely remains unknown. In the present study, we have evaluated anticancer potential of INT alone or in combination with cisplatin (CIS) in non-small cell lung carcinoma (A549) cells. Treatment with INT alone reduced the viability of A549 cells in a dose-dependent manner. Interestingly, the combination of low doses of INT and CIS exerted a synergistic effect and induced apoptosis as evident by DNA fragmentation and Annexin V positive cells. Enhanced Bax:Bcl-2 ratio, loss of Δψm, cytochrome c release, cleavage of caspase 3 and PARP1 strongly corroborated our findings. Further, increased expression of p53, p38 MAPK and their phosphorylated counterparts, loss of clonogenicity and reduced migration potential were also recorded with INT + CIS treatment. Most interestingly, INT could not induce any significant cell death in primary mouse embryonic fibroblasts (MEFs). Moreover, no additive or synergistic effect was noted with INT + CIS in MEFs under similar treatment conditions. In conclusion, INT has a selective anticancer potential and could synergize cytotoxicity of CIS. Therefore, the combination of INT and CIS may serve as an effective anticancer strategy for the treatment of non-small cell lung carcinoma.



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Comparative genomics of a drug-resistant Pseudomonas aeruginosa panel and the challenges of antimicrobial resistance prediction from genomes

Abstract
Antimicrobial resistance (AMR) is now recognized as a global threat to human health. The accessibility of microbial whole-genome sequencing offers an invaluable opportunity for resistance surveillance via the resistome, i.e. the genes and mutations underlying AMR. Unfortunately, AMR prediction from genomic data remains extremely challenging, especially for species with a large pan-genome. One such organism, for which multidrug-resistant (MDR) isolates are frequently encountered in the clinic, is Pseudomonas aeruginosa. This study focuses on a commercially available panel of 7 MDR P. aeruginosa strains. The main goals were to sequence and compare these strains' genomes, attempt to predict AMR from whole genomes using two different methods, and determine whether this panel could be an informative complement to the international P. aeruginosa reference panel. As expected, the results highlight the complexity of associating genotype and AMR phenotype in P. aeruginosa, mainly due to the intricate regulation of resistance mechanisms. Our results also urge caution in the interpretation of predicted resistomes regarding the occurrence of gene identity discrepancies between strains. We envision that, in addition to accounting for the genomic diversity of P. aeruginosa, future development of predictive tools will need to incorporate a transcriptomic, proteomic and/or metabolomic component.

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Drugging the Cancers Addicted to DNA Repair.

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Drugging the Cancers Addicted to DNA Repair.

J Natl Cancer Inst. 2017 11 01;109(11):

Authors: Nickoloff JA, Jones D, Lee SH, Williamson EA, Hromas R

Abstract
Defects in DNA repair can result in oncogenic genomic instability. Cancers occurring from DNA repair defects were once thought to be limited to rare inherited mutations (such as BRCA1 or 2). It now appears that a clinically significant fraction of cancers have acquired DNA repair defects. DNA repair pathways operate in related networks, and cancers arising from loss of one DNA repair component typically become addicted to other repair pathways to survive and proliferate. Drug inhibition of the rescue repair pathway prevents the repair-deficient cancer cell from replicating, causing apoptosis (termed synthetic lethality). However, the selective pressure of inhibiting the rescue repair pathway can generate further mutations that confer resistance to the synthetic lethal drugs. Many such drugs currently in clinical use inhibit PARP1, a repair component to which cancers arising from inherited BRCA1 or 2 mutations become addicted. It is now clear that drugs inducing synthetic lethality may also be therapeutic in cancers with acquired DNA repair defects, which would markedly broaden their applicability beyond treatment of cancers with inherited DNA repair defects. Here we review how each DNA repair pathway can be attacked therapeutically and evaluate DNA repair components as potential drug targets to induce synthetic lethality. Clinical use of drugs targeting DNA repair will markedly increase when functional and genetic loss of repair components are consistently identified. In addition, future therapies will exploit artificial synthetic lethality, where complementary DNA repair pathways are targeted simultaneously in cancers without DNA repair defects.

PMID: 28521333 [PubMed - indexed for MEDLINE]



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Downregulation of the IFNAR1 chain of type 1 interferon receptor contributes to the maintenance of the haematopoietic stem cells

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Discussing the predictive, prognostic, and therapeutic value of germline DNA-repair gene mutations in metastatic prostate cancer patients

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Depletion of carbonic anhydrase IX abrogates hypoxia-induced overexpression of stanniocalcin-1 in triple negative breast cancer cells

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A rapid and systemic complete response to stereotactic body radiation therapy and pembrolizumab in a patient with metastatic renal cell carcinoma

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Cabozantinib inhibits tumor growth and metastasis of a patient-derived xenograft model of papillary renal cell carcinoma with MET mutation

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Treatments for Metastatic Prostate Cancer (mPC): A Review of Costing Evidence

Abstract

Background

Prostate cancer (PC) is the most common cancer in Western countries. More than one third of PC patients develop metastatic disease, and the 5-year expected survival in distant disease is about 35%. During the last few years, new treatments have been launched for metastatic castrate-resistant prostate cancer (mCRPC).

Objectives

We aimed to review the current literature on health economic analysis on the treatment of metastatic prostate cancer (mPC), compare the studies, summarize the findings and make the results available to administrators and decision makers.

Methods

A systematic literature search was done for economic evaluations (cost-minimization, cost-effectiveness, cost-utility, cost-of-illness, cost-of-drug, and cost-benefit analyses). We employed the PubMed® search engine and searched for publications published between 2012 and 2016. The terms used were "prostate cancer", "metastatic" and "cost". An initial screening of all headlines was performed, selected abstracts were analysed, and finally the full papers investigated. Study characteristics, treatment and comparator, country, type of evaluation, perspective, year of value, time horizon, efficacy data, discount rate, total costs and sensitivity analysis were analysed. The quality was assessed using the Quality of Health Economic Studies (QHES) instrument.

Results

A total of 227 publications were detected and screened, 58 selected for full-text assessment and 31 included in the final analyses. Despite the significant international literature on the treatment of mCRPC, there were only 15 studies focusing on cost-effectiveness analysis (CEA). Medical treatment constituted two thirds of the selected studies. Significant costs in the treatment of mCRPC were disclosed. In the pre-docetaxel setting, both abiraterone acetate (AA) and enzalutamide were concluded beyond accepted cost/quality-adjusted life year limits. In the docetaxel refractory setting, most studies concluded that enzalutamide was cost-effective and superior to AA. In most studies, cabazitaxel was not recommended, because of high cost. Looking at bone-targeting drugs, generic zoledronic acid (ZA) was recommended. External beam radiotherapy (EBRT) was analysed in three studies, and single fraction radiotherapy was concluded to be cost saving. Radium-223 was documented as beneficial, but costly. The quality of the studies was generally good, but sensitivity analyses, discounting and the measurement of health outcomes were present in less than two thirds of the selected studies.

Conclusions

The treatment of mCRPC was associated with significant cost. In the post-docetaxel setting, single fraction radiotherapy and enzalutamide were considered cost-effective in most studies. Generic ZA was the recommended bone-targeting therapy.



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Cancers, Vol. 9, Pages 98: EMT/MET at the Crossroad of Stemness, Regeneration and Oncogenesis: The Ying-Yang Equilibrium Recapitulated in Cell Spheroids

Cancers, Vol. 9, Pages 98: EMT/MET at the Crossroad of Stemness, Regeneration and Oncogenesis: The Ying-Yang Equilibrium Recapitulated in Cell Spheroids

Cancers doi: 10.3390/cancers9080098

Authors: Elvira Forte Isotta Chimenti Paolo Rosa Francesco Angelini Francesca Pagano Antonella Calogero Alessandro Giacomello Elisa Messina

The epithelial-to-mesenchymal transition (EMT) is an essential trans-differentiation process, which plays a critical role in embryonic development, wound healing, tissue regeneration, organ fibrosis, and cancer progression. It is the fundamental mechanism by which epithelial cells lose many of their characteristics while acquiring features typical of mesenchymal cells, such as migratory capacity and invasiveness. Depending on the contest, EMT is complemented and balanced by the reverse process, the mesenchymal-to-epithelial transition (MET). In the saving economy of the living organisms, the same (Ying-Yang) tool is integrated as a physiological strategy in embryonic development, as well as in the course of reparative or disease processes, prominently fibrosis, tumor invasion and metastasis. These mechanisms and their related signaling (e.g., TGF-β and BMPs) have been effectively studied in vitro by tissue-derived cell spheroids models. These three-dimensional (3D) cell culture systems, whose phenotype has been shown to be strongly dependent on TGF-β-regulated EMT/MET processes, present the advantage of recapitulating in vitro the hypoxic in vivo micro-environment of tissue stem cell niches and their formation. These spheroids, therefore, nicely reproduce the finely regulated Ying-Yang equilibrium, which, together with other mechanisms, can be determinant in cell fate decisions in many pathophysiological scenarios, such as differentiation, fibrosis, regeneration, and oncogenesis. In this review, current progress in the knowledge of signaling pathways affecting EMT/MET and stemness regulation will be outlined by comparing data obtained from cellular spheroids systems, as ex vivo niches of stem cells derived from normal and tumoral tissues. The mechanistic correspondence in vivo and the possible pharmacological perspective will be also explored, focusing especially on the TGF-β-related networks, as well as others, such as SNAI1, PTEN, and EGR1. This latter, in particular, for its ability to convey multiple types of stimuli into relevant changes of the cell transcriptional program, can be regarded as a heterogeneous "stress-sensor" for EMT-related inducers (growth factor, hypoxia, mechano-stress), and thus as a therapeutic target.



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Characterization of Chicken Splenic-Derived Dendritic Cells Following Vaccine and Very Virulent Strains of Infectious Bursal Disease Virus Infection.

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Characterization of Chicken Splenic-Derived Dendritic Cells Following Vaccine and Very Virulent Strains of Infectious Bursal Disease Virus Infection.

Avian Dis. 2016 Dec;60(4):739-751

Authors: Yasmin AR, Yeap SK, Hair-Bejo M, Omar AR

Abstract
Studies have shown that infectious bursal disease virus (IBDV) infects lymphoid cells, mainly B cells and macrophages. This study was aimed to examine the involvement of chicken splenic-derived dendritic cells (ch-sDCs) in specific-pathogen-free chickens following inoculation with IBDV vaccine strain (D78) and a very virulent (vv) strain (UPM0081). Following IBDV infection, enriched activated ch-sDCs were collected by using the negative selection method and were examined based on morphology and immunophenotyping to confirm the isolation method for dendritic cells (DCs). The presence of IBDV on enriched activated ch-sDCs was analyzed based on the immunofluorescence antibody test (IFAT), flow cytometry, and quantitative real-time PCR (RT-qPCR) while the mRNAs of several cytokines were detected using RT-qPCR. The isolated ch-sDCs resembled typical DC morphologies found in mammals by having a veiled shape and they grew in clusters. Meanwhile, the expression of DC maturation markers, namely CD86 and MHCII, were increased at day 2 and day 3 following vvIBDV and vaccine strain inoculation, respectively, ranging from 10% to 40% compared to the control at 2.55% (P < 0.05). At day 3 postinfection, IBDV VP3 proteins colocalized with CD86 were readily detected via IFAT and flow cytometry in both vaccine and vvIBDV strains. In addition, enriched activated ch-sDCs were also detected as positive based on the VP4 gene by RT-qPCR; however, a higher viral load was detected on vvIBDV compared to the vaccine group. Infection with vaccine and vvIBDV strains induced the enriched activated ch-sDCs to produce proinflammatory cytokines and Th1-like cytokines from day 3 onward; however, the expressions were higher in the vvIBDV group (P < 0.05). These data collectively suggest that enriched activated ch-sDCs were permissive to IBDV infection and produced a strong inflammatory and Th1-like cytokine response following vvIBDV infection as compared to the vaccine strain.

PMID: 27902915 [PubMed - indexed for MEDLINE]



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Statistical science: a grammar for research

Abstract

I greatly appreciate the invitation to give this lecture with its century long history. The title is a warning that the lecture is rather discursive and not highly focused and technical. The theme is simple. That statistical thinking provides a unifying set of general ideas and specific methods relevant whenever appreciable natural variation is present. To be most fruitful these ideas should merge seamlessly with subject-matter considerations. By contrast, there is sometimes a temptation to regard formal statistical analysis as a ritual to be added after the serious work has been done, a ritual to satisfy convention, referees, and regulatory agencies. I want implicitly to refute that idea.



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An in vitro model of azithromycin-induced persistent Chlamydia trachomatis infection

Abstract
Single-dose azithromycin is recommended for treating Chlamydia trachomatis infections. Here, we established an in vitro cell model of azithromycin-induced persistent infection. Azithromycin inhibited the replication of C. trachomatis in a dose–time-dependent manner. Electron microscopy indicated that small inclusions in the induced model contained enlarged, aberrant and non-infectious reticulate bodies. RT-PCR showed that C. trachomatis still has the ability to express the unprocessed 16S rRNA gene in the model and that C. trachomatis recovered after the removal of azithromycin with a peak recovery time of 24 h. The mutations in 23S rRNA, L4 and L22 genes were not found in persistent infection, and qRT-PCR analysis showed that the relative expression level of euo in azithromycin treated infection was upregulated while omcB was downregulated. In summary, this study provides a novel in vitro cell model to examine the characteristics of azithromycin-induced persistent infection and contribute to the development of treatments for C. trachomatis infection.

http://ift.tt/2ubNdl6

Investigating differences in the ability of XplA/B-containing bacteria to degrade the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)

Abstract
The xenobiotic hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is a toxic explosive and environmental pollutant. This study examines three bacterial species that degrade RDX, using it as a sole source of nitrogen for growth. Although isolated from diverse geographical locations, the species contain near identical copies of genes encoding the RDX-metabolising cytochrome P450, XplA and accompanying reductase, XplB. Sequence analysis indicates a single evolutionary origin for xplA and xplB as part of a genomic island, which has been distributed around the world via horizontal gene transfer. Despite the fact that xplA and xplB are highly conserved between species, Gordonia sp. KTR9 and Microbacterium sp. MA1 degrade RDX more slowly than Rhodococcus rhodochrous 11Y. Both Gordonia sp. KTR9 and Microbacterium sp. MA1 were found to contain single base-pair mutations in xplB which, following expression and purification, were found to encode inactive XplB protein. Additionally, the Gordonia sp. KTR9 XplB was fused to glutamine synthetase, which would be likely to sterically inhibit XplB activity. Although the glutamine synthetase is fused to XplB and truncated by 71 residues, it was found to be active. Glutamine synthetase has been implicated in the regulation of nitrogen levels; controlling nitrogen availability will be important for effective bioremediation of RDX.

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Peculiar citric acid cycle of hydrothermal vent chemolithoautotroph Hydrogenovibrio crunogenus , and insights into carbon metabolism by obligate autotrophs

Abstract
The genome sequence of the obligate chemolithoautotroph Hydrogenovibrio crunogenus paradoxically predicts a complete oxidative citric acid cycle (CAC). This prediction was tested by multiple approaches including whole cell carbon assimilation to verify obligate autotrophy, phylogenetic analysis of CAC enzyme sequences and enzyme assays. Hydrogenovibrio crunogenus did not assimilate any of the organic compounds provided (acetate, succinate, glucose, yeast extract, tryptone). Enzyme activities confirmed that its CAC is mostly uncoupled from the NADH pool. 2-Oxoglutarate:ferredoxin oxidoreductase activity is absent, though pyruvate:ferredoxin oxidoreductase is present, indicating that sequence-based predictions of substrate for this oxidoreductase were incorrect, and that H. crunogenus may have an incomplete CAC. Though the H. crunogenus CAC genes encode uncommon enzymes, the taxonomic distribution of their top matches suggests that they were not horizontally acquired. Comparison of H. crunogenus CAC genes to those present in other 'Proteobacteria' reveals that H. crunogenus and other obligate autotrophs lack the functional redundancy for the steps of the CAC typical for facultative autotrophs and heterotrophs, providing another possible mechanism for obligate autotrophy.

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Optimization of therapy against Pseudomonas aeruginosa with ceftazidime and meropenem using chemostats as model for infections

Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that can cause life-threatening infections in patients admitted to intensive care units. Resistance rapidly develops against two drugs of choice: ceftazidime and meropenem. Several therapeutic protocols were compared for reduction in viable cells and limiting development of resistance. Chemostat cultures were exposed to antibiotic concentrations measured in the blood of patients at low (5th percentile), medium (50th percentile) or high (95th percentile) levels in several therapy protocols to simulate therapy. Cultures exposed to ceftazidime recovered after 1 day at low, 2 days at medium and 3 days at high concentrations and developed corresponding levels of resistance. Patterns were very similar for meropenem except that recovery was delayed. Fluctuating levels and intermittent treatment achieved similar reduction of cell numbers at lower resistance costs. Treatment alternating ceftazidime and meropenem reduced cell numbers more than monotherapy, while strongly limiting resistance. Combination therapy was even more effective in both respects. Therapeutic goals are best reached with least risk of resistance when ceftazidime and meropenem are used in combination or alternating, at the highest concentrations the patient can endure. Monotherapy should also apply the highest concentration that is safe for the shortest time that achieves treatment objectives.

http://ift.tt/2tvKwu5

A Burkholderia endophyte of the ancient maize landrace Chapalote utilizes c-di-GMP-dependent and independent signaling to suppress diverse plant fungal pathogen targets

Abstract
Chapalote is a maize (corn) landrace grown continuously by subsistence farmers in the Americas since 1000 BC, valued in part for its broad-spectrum pathogen resistance. Previously, we showed that Chapalote possesses a bacterial endophyte, Burkholderia gladioli strain 3A12, which suppresses growth of Sclerotinia homoeocarpa, a fungal pathogen of a maize relative, used as a model system. Ten mutants that lost the anti-pathogen activities were identified, corresponding to five genes. However, S. homoeocarpa is not a known maize pathogen; hence, the relevance of these anti-fungal mechanisms to its ancient host has not been clear. Here, the strain 3A12 mutants were tested against a known pathogen of maize and many crops, Rhizoctonia solani. Microscopy established that wild-type 3A12 swarms towards, and attaches onto, the pathogen, forming microcolonies, resulting in hyphal cleavage. Analysis of the mutants revealed that 3A12 uses common downstream gene products (e.g. fungicides) to suppress the growth of both S. homoeocarpa and R. solani, but apparently different upstream regulatory machinery, with the former, but not latter pathogen, requiring YajQ, a receptor for the secondary messenger c-di-GMP. We conclude that B. gladioli strain 3A12, an endophyte of an ancient maize, employs both c-di-GMP-dependent and independent signaling to target diverse fungal pathogens.

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Comparison of four DNA extraction methods for comprehensive assessment of 16S rRNA bacterial diversity in marine biofilms using high-throughput sequencing

Abstract
High-throughput DNA sequencing technologies are increasingly used for the metagenomic characterisation of microbial biodiversity. However, basic issues, such as the choice of an appropriate DNA extraction method, are still not resolved for non-model microbial communities. This study evaluates four commonly used DNA extraction methods for marine periphyton biofilms in terms of DNA yield, efficiency, purity, integrity and resulting 16S rRNA bacterial diversity. Among the tested methods, the Plant DNAzol® Reagent (PlantDNAzol) and the FastDNA® SPIN Kit for Soil (FastDNA Soil) methods were best suited to extract high quantities of DNA (77–130 μg g wet wt−1). Lower amounts of DNA were obtained (<37 μg g wet wt−1) with the Power Plant® Pro DNA Isolation Kit (PowerPlant) and the Power Biofilm® DNA Isolation Kit (PowerBiofilm) methods, but integrity and purity of the extracted DNA were higher. Results from 16S rRNA amplicon sequencing demonstrate that the choice of a DNA extraction method significantly influences the bacterial community profiles generated. A higher number of bacterial OTUs were detected when DNA was extracted with the PowerBiofilm and the PlantDNAzol methods. Overall, this study demonstrates the potential bias in metagenomic diversity estimates associated with different DNA extraction methods.

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The yeast Mig1 transcriptional repressor is dephosphorylated by glucose-dependent and -independent mechanisms

Abstract
A yeast Saccharomyces cerevisiae Snf1 kinase, an analog of mammalian AMPK, regulates glucose derepression of genes required for utilization of alternative carbon sources through the transcriptional repressor Mig1. It has been suggested that the Glc7-Reg1 phosphatase dephosphorylates Mig1. Here we report that Mig1 is dephosphorylated by Glc7-Reg1 in an apparently glucose-dependent mechanism but also by a mechanism independent of glucose and Glc7-Reg1. In addition to serine/threonine phosphatases another process including tyrosine phosphorylation seems crucial for Mig1 regulation. Taken together, Mig1 dephosphorylation appears to be controlled in a complex manner, in line with the importance for rapid and sensitive regulation upon altered glucose concentrations in the growth medium.

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Antagonistic regulation of cyclin expression by the bZIP transcription factors Pcr1 and Atf1 during G2/M transition

Abstract
The transcription factor Atf1 is known to promote cell survival during various stress conditions in Schizosaccharomyces pombe by activating the expression of appropriate genes. It can also activate transcription of other important genes responsible for cell cycle progression. An Atf1-dependent increase in the expression of cell division promoting genes will oppose activation of checkpoints necessary to ensure repairs and cell survival during stress. Hence, selective inhibition of the cell cycle-related functions of Atf1 would be indispensable for cellular survival during stress. Here we present evidence in favour of selective inhibition of Atf1's ability to activate cdc13+ transcription. We show that the transcription factor Pcr1 can specifically inhibit the recruitment of Atf1 on cdc13 promoter and thereby prevent Atf1-mediated mitotic acceleration. We also show that this opposition of Atf1 functions by Pcr1 extends to the G1-S transition event as well. Altogether these results suggest a previously unknown antagonistic function of Atf1 and Pcr1 in regulating Cdc13 expression during cell cycle progression.

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Occurrence of aminoglycoside-modifying enzymes among isolates of Escherichia coli exhibiting high levels of aminoglycoside resistance isolated from Korean cattle farms

Abstract
This study investigated 247 Escherichia coli isolates collected from four cattle farms to characterize aminoglycoside-modifying enzyme (AME) genes, their plasmid replicons and transferability. Out of 247 isolates a high number of isolates (total 202; 81.78%) were found to be resistant to various antibiotics by disc diffusion. Of the 247 strains, 139 (56.3%) were resistant to streptomycin, and other antibiotic resistances followed as tetracycline (12.15%), ampicillin (7%), chloramphenicol (5.7%) and trimethoprim-sulfamethoxazole (0.8%). Among 247 isolates B1 was the predominant phylogenetic group identified comprising 151 isolates (61.1%), followed by groups A (27.9%), D (7%) and B2 (4%). Out of 139 isolates investigated for AME, 130 (93.5%) isolates carried at least one AME gene. aph3″-1a and aph3″-1b (46%) were the principal genes detected, followed by aac3-IVa (34.5%). ant2″-1a was the least detected gene (2.2%). Nine (6.5%) strains carried no AME genes. Twelve (63.2%) among 19 isolates transferred an AME gene to a recipient and aph3΄-1a was the dominant transferred gene. Transferability mainly occurred via the IncFIB replicon type (52.6%). Pulsed-field gel electrophoresis typing demonstrated a higher degree of diversity with 14 distinct cluster types. This result suggests that commensal microflora from food-producing animals has a tremendous ability to harbor and transfer AME genes, and poses a potential risk by dissemination of resistance to humans through the food chain.

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Current and future therapies for Pseudomonas aeruginosa infection in patients with cystic fibrosis

Abstract
Pseudomonas aeruginosa opportunistically infects the airways of patients with cystic fibrosis and causes significant morbidity and mortality. Initial infection can often be eradicated though requires prompt detection and adequate treatment. Intermittent and then chronic infection occurs in the majority of patients. Better detection of P. aeruginosa infection using biomarkers may enable more successful eradication before chronic infection is established. In chronic infection P. aeruginosa adapts to avoid immune clearance and resist antibiotics via efflux pumps, β-lactamase expression, reduced porins and switching to a biofilm lifestyle. The optimal treatment strategies for P. aeruginosa infection are still being established, and new antibiotic formulations such as liposomal amikacin, fosfomycin in combination with tobramycin and inhaled levofloxacin are being explored. Novel agents such as the alginate oligosaccharide OligoG, cysteamine, bacteriophage, nitric oxide, garlic oil and gallium may be useful as anti-pseudomonal strategies, and immunotherapy to prevent infection may have a role in the future. New treatments that target the primary defect in cystic fibrosis, recently licensed for use, have been associated with a fall in P. aeruginosa infection prevalence. Understanding the mechanisms for this could add further strategies for treating P. aeruginosa in future.

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Quick change: post-transcriptional regulation in Pseudomonas

Abstract
Pseudomonas species have evolved dynamic and intricate regulatory networks to fine-tune gene expression, with complex regulation occurring at every stage in the processing of genetic information. This approach enables Pseudomonas to generate precise individual responses to the environment in order to improve their fitness and resource economy. The weak correlations we observe between RNA and protein abundance highlight the significant regulatory contribution of a series of intersecting post-transcriptional pathways, influencing mRNA stability, translational activity and ribosome function, to Pseudomonas environmental responses. This review examines our current understanding of three major post-transcriptional regulatory systems in Pseudomonas spp.; Gac/Rsm, Hfq and RimK, and presents an overview of new research frontiers, emerging genome-wide methodologies, and their potential for the study of global regulatory responses in Pseudomonas.

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Plasmid transfer efficiency using Lactoccocus lactis strains depends on invasiveness status but also on plasmid copy number

Abstract
Lactic acid bacteria as Lactococcus lactis are used as vector for protein but also DNA delivery into intestinal cells in vitro and in vivo. For the plasmid delivery strategy, the plasmid copy number per bacteria (PCN) is thus of great importance. The aim of this paper is to determine the physiological conditions when PCN is the highest in the bacteria. PCN was characterized by qPCR in five different recombinant Lactococcus lactis strains, containing one (mono-) or two different plasmids (biplasmidic), at exponential or stationary phase. We showed that in all cases but one, PCN is higher at exponential than stationary phase. PCN seems to depend on (i) monoplasmidic or biplasmidic strain; (ii) origin of replication of the plasmid; and (iii) the DNA load of the bacteria. Then we studied plasmid transfer in vitro from recombinant L. lactis to eukaryotic COS-7 cells using culture at exponential or stationary phase. We showed that plasmid transfer can be improved in vitro by using bacteria at exponential phase.

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Informed Consent and Nitrous Oxide for Obstetric Analgesia.

No abstract available

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In Response.

No abstract available

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Absolute Postoperative B-Type Natriuretic Peptide Concentrations, but Not Their General Trend, Are Associated With 12-Month, All-Cause Mortality After On-Pump Cardiac Surgery.

BACKGROUND: B-type natriuretic peptide (BNP) is a predictor of mortality after on-pump cardiac surgery. However, previous limited and heterogeneous studies have focused on peak concentrations at 3 to 5 days after surgery and may not offer clinicians much help in early decision-making. After confirming the predictive value of first-postoperative-day BNP in a preliminary analysis, we explored the association between isolated second-postoperative-day BNP concentrations, second-day BNP concentrations in conjunction with first-day BNP concentrations, and the change in BNP (ie, [DELTA]BNP) from the first to the second postoperative day and 12-month, all-cause mortality. METHODS: We included consecutive patients undergoing on-pump cardiac surgery in this observational, secondary analysis of prospectively collected data. We analyzed biomarkers on the first and second postoperative day. [DELTA]BNP was defined as BNP on the second postoperative day minus BNP on the first postoperative day. The primary end point was 12-month, all-cause mortality. The secondary end point was a composite of major adverse cardiac events (MACEs) at 12 months and/or all-cause mortality at 12 months. MACE was defined as nonfatal cardiac arrest, myocardial infarction, and congestive heart failure. The association between BNP and outcomes was examined by receiver operating characteristic curves, as well as univariate and multivariable logistic regression, adjusting for the EuroSCORE II, cross-clamp time, and first-postoperative-day troponin T. RESULTS: We included 1199 patients in the preliminary analysis focused on BNP on postoperative day 1. In the analyses examining BNP variables requiring second-postoperative-day BNP measurement (n = 708), we observed 66 (9.3%) deaths, 48 (6.8%) MACE, and 104 (14.7%) deaths and/or MACE. Both first- and second-postoperative-day BNP were significant independent predictors of all-cause, 12-month mortality per 100 ng/L increase (adjusted odds ratio [aOR], 1.040 [95% confidence interval (CI), 1.019-1.065] and 1.064 [95% CI, 1.031-1.105], respectively). When used in conjunction with one another, first-day BNP was not significant (aOR, 1.021 [95% CI, 0.995-1.048]), while second-day BNP remained significant (aOR, 1.046 [95% CI, 1.008-1.091]). The [DELTA]BNP per 100 ng/L increase was not associated with 12-month, all-cause mortality in the univariable (OR, 0.977 [95% CI, 0.951-1.007]) or multivariable analysis (aOR, 0.989 [95% CI, 0.962-1.021]). CONCLUSIONS: Both absolute concentrations of first- and second-postoperative-day BNP are independent predictors of 12-month, all-cause mortality. When modeled together, second-postoperative-day BNP is more predictive of 12-month, all-cause mortality. Although intuitively appealing, the change in BNP from the first to the second postoperative day is a complex variable and should not routinely be used for prognostication. (C) 2017 International Anesthesia Research Society

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Antibiotics and the Anesthesiologist: Is There a "Consensus?".

No abstract available

http://ift.tt/2eWcB8o

Informed Consent and Nitrous Oxide for Labor Analgesia.

No abstract available

http://ift.tt/2hasUPV

Antifragile Systems and Physician Wellness.

No abstract available

http://ift.tt/2eVei64

The WFSA Global Anesthesia Workforce Survey.

BACKGROUND: Safe anesthesia and surgical care are not available when needed for 5 billion of the world's 7 billion people. There are major deficiencies in the specialist surgical workforce in many parts of the world, and specific data on the anesthesia workforce are lacking. METHODS: The World Federation of Societies of Anaesthesiologists conducted a workforce survey during 2015 and 2016. The aim of the survey was to collect detailed information on physician anesthesia provider (PAP) and non-physician anesthesia provider (NPAP) numbers, distribution, and training. Data were categorized according to World Health Organization regional groups and World Bank income groups. RESULTS: We obtained information for 153 of 197 countries, representing 97.5% of the world's population. There were marked differences in the density of PAPs between World Health Organization regions and between World Bank income groups, ranging from 0 to over 20 PAP per 100,000 population. Seventy-seven countries reported a PAP density of

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Comparison Between the Cobra Perilaryngeal Airway and Laryngeal Mask Airways Under General Anesthesia: A Systematic Review and Meta-analysis.

The complication rate and efficacy of the Cobra Perilaryngeal Airway (CobraPLA) and laryngeal mask airways (LMAs(R)) have been evaluated in the published literature, but the conclusions have been inconsistent. The aim of this systematic review and meta-analysis was thus to assess the performance of the CobraPLA and LMAs under general anesthesia. We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials comparing the CobraPLA with LMAs under general anesthesia. The LMAs used for comparison were the classic LMA (CLMA) and the unique LMA (ULMA). The random effect model was used if heterogeneity was observed, otherwise the fixed effect model was used. Seventeen randomized controlled trials were included; number of studies analyzed for each result are different and were up to 10. The current result suggests that no significant difference between the devices in the insertion success rate at the first attempt. The success rate of first insertion of the CobraPLA was not different from the rates for the CLMA and the ULMA (relative risk: 0.95, 95% confidence interval [CI], 0.91-1.00). CobraPLA insertion was not different from CLMA and ULMA insertion. The CobraPLA provided an oropharyngeal leak pressure higher than that provided by the CLMA (weight mean difference: 3.90, 95% CI, [1.59-6.21] cmH2O) and ULMA (weight mean difference: 6.57, 95% CI, [4.30-8.84] cmH2O). We also found a higher likelihood of blood staining in the airway with the CobraPLA than with the CLMA. In our research, the principal finding of our meta-analysis is that the success rate of first insertion of the CobraPLA was not different from the rate for each of the CLMA and the ULMA, which featured a short learning curve implying its ease of insertion. There was also no significant difference in the incidence of the best view (with a score of 4) obtained with the CobraPLA compared with the other 2 devices. The CobraPLA does seem to be superior to the CLMA and ULMA in providing a higher oropharyngeal leak pressure. The data were insufficient to establish differences in airway adverse events between the groups except for blood staining in the devices, although mucosal trauma occurred more frequently with the Cobra PLA device than with the CLMA and the ULMA. (C) 2017 International Anesthesia Research Society

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