Τρίτη, 24 Απριλίου 2018

Genomic Characterization of Nonclonal mcr-1-Positive Multidrug-Resistant Klebsiella pneumoniae from Clinical Samples in Thailand

Microbial Drug Resistance, Ahead of Print.


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Rapid Integration of Multi-copy Transgenes Using Optogenetic Mutagenesis in Caenorhabditis elegans

Stably transmitted transgenes are indispensable for labeling cellular components and manipulating cellular functions. In Caenorhabditis elegans, transgenes are generally generated as inheritable multi-copy extrachromosomal arrays, which can be stabilized in the genome through a mutagenesis-mediated integration process. Standard methods to integrate extrachromosomal arrays primarily use protocols involving ultraviolet light plus trimethylpsoralen or gamma- or X-ray irradiation, which are laborious and time-consuming. Here, we describe a one-step integration method, following germline-mutagenesis induced by mini Singlet Oxygen Generator (miniSOG). Upon blue light treatment, miniSOG tagged to histone (Histone-miniSOG) generates reactive oxygen species (ROS) and induces heritable mutations, including DNA double-stranded breaks. We demonstrate that we can bypass the need to first establish extrachromosomal transgenic lines by coupling microinjection of desired plasmids with blue light illumination on Histone-miniSOG worms to obtain integrants in the F3 progeny. We consistently obtained more than one integrant from 12 injected animals in two weeks. This optogenetic approach significantly reduces the amount of time and labor for transgene integration. Moreover, it enables to generate stably expressed transgenes that cause toxicity in animal growth.



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Why EMS agencies should change their definition of intubation success

Dr. Jeffrey Jarvis, medical director for Williamson County (Texas) EMS, will discuss why delayed sequence intubation is a cure for Rapid Sequenced Death at EMS PRO conference

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Learn how to combat sleep deprivation and fatigue in EMS

Amy Eisenhauer to discuss health risks and performance impact of disrupted sleep, as well as strategies for overcoming these challenges, as part of EMS PRO conference

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3 ways to overcome your fear of pediatric patients

Providing effective pediatric care starts with confronting your challenges with children

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Preliminary study of magnetically controlled capsule gastroscopy for diagnosing superficial gastric neoplasia

Magnetically controlled capsule gastroscopy (MCCG) is a newly developed non-invasive method designed for gastric examination. Although favourable diagnostic accuracy has been reported, there is little if any data about its ability to diagnose gastric cancer.

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Lymphatic imaging and intervention in a pediatric population: Anesthetic considerations

Pediatric Anesthesia, EarlyView.


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Safety of anesthesia for children with mucopolysaccharidoses: A retrospective analysis of 54 patients

Pediatric Anesthesia, EarlyView.


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Genomic insights into the origin and diversification of late maritime hunter-gatherers from the Chilean Patagonia [Genetics]

Patagonia was the last region of the Americas reached by humans who entered the continent from Siberia ∼15,000–20,000 y ago. Despite recent genomic approaches to reconstruct the continental evolutionary history, regional characterization of ancient and modern genomes remains understudied. Exploring the genomic diversity within Patagonia is not just a valuable...

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Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing [Genetics]

Epigenetic silencing can be mediated by various mechanisms, and many regulators remain to be identified. Here, we report a genome-wide siRNA screening to identify regulators essential for maintaining gene repression of a CMV promoter silenced by DNA methylation. We identified CSE1L (chromosome segregation 1 like) as an essential factor for...

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W.Va. fire chief makes TIME’s top 100 influential people list

By EMS1 Staff HUNTINGTON, W.Va. — A fire chief who has gained national attention for being a leader in the fight against the opioid crisis was named one of TIME's Top 100 Influential People of 2018. WSAZ reported that Huntington Fire Department Chief Jan Rader, who was recently featured in the Netflix documentary "Heroin(e)," said she is "honored" to be recognized ...

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A-to-I RNA editing — immune protector and transcriptome diversifier

A-to-I RNA editing — immune protector and transcriptome diversifier

A-to-I RNA editing — immune protector and transcriptome diversifier, Published online: 24 April 2018; doi:10.1038/s41576-018-0006-1

Next-generation sequencing technologies have enabled the comparison of editomes from multiple individuals and from multiple species. The results have changed our understanding of the extent and distribution of A-to-I editing and its role in evolution and disease.

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Molecular cloning and characterization of a novel salt-specific responsive WRKY transcription factor gene IlWRKY2 from the halophyte Iris lactea var. chinensis

Abstract

Iris lactea var. chinensis is a perennial herbaceous halophyte with high salt tolerance and ornamental value. Previous RNA sequencing analysis revealed a transcription factor gene IlWRKY2 expression was upregulated by salt stress. To obtain the full-length sequence, the basic characteristics of IlWRKY2 and its expression pattern under salt stress. Full-length cDNA of IlWRKY2 was cloned by 3′/5′ RACE based on the intermediate sequence obtained by RNA sequencing analysis. Structure analysis of IlWRKY2 were performed by Compute pI/MW tool, PSIPRED and SWISS-MODEL analysis. Sequence analysis of IlWRKY2 were performed by BLAST program, DNAman software, MEGA software and MEME program. IlWRKY2 expression pattern was analyzed by quantitative real-time polymerase chain reaction. The open reading frame of IlWRKY2 is 1338 bp in length, which encodes a protein of 446 amino acids. Amino acid sequence analysis revealed that the IlWRKY2 contains one WRKY domains with a zinc finger motif C–X5–C–X23–H–X–H. Phylogenetic analysis showed that the IlWRKY2 was much closer to EgWRKY41 from Elaeis guineensis and MaWRKY42 from Musa acuminata subsp. malaccensis. Furthermore, the expression of IlWRKY2 in I. lactea var. chinensis shoots was upregulated by different concentrations of NaCl treatment and increased 16-fold after treatment with 200 mM NaCl for 12 h. Obtained the full-length cDNA of IlWRKY2 which belongs to Group II-b WRKY subfamily. IlWRKY2 expression was obviously induced by salt stress in I. lactea var. chinensis shoots and it may play an important role in halophyte I. lactea var. chinensis adaptation to environmental salt stress.



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A-to-I RNA editing — immune protector and transcriptome diversifier



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Structural variation in the 3D genome

Structural variation in the 3D genome

Structural variation in the 3D genome, Published online: 24 April 2018; doi:10.1038/s41576-018-0007-0

Recent studies show that structural variation can alter the genome architecture, leading to changes in the regulation of gene expression that cause disease. The authors review the role of genetic structural variation in disease and the pathogenic potential of changes to the 3D genome.

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Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy

Abstract

Progressive microcephaly and neurodegeneration are genetically heterogenous conditions, largely associated with genes that are essential for the survival of neurons. In this study, we interrogate the genetic etiology of two siblings from a non-consanguineous family with severe early onset of neurological manifestations. Whole exome sequencing identified novel compound heterozygous mutations in VARS that segregated with the proband: a missense (c.3192G>A; p.Met1064Ile) and a splice site mutation (c.1577-2A>G). The VARS gene encodes cytoplasmic valyl-tRNA synthetase (ValRS), an enzyme that is essential during eukaryotic translation. cDNA analysis on patient derived fibroblasts revealed that the splice site acceptor variant allele led to nonsense mediated decay, thus resulting in a null allele. Three-dimensional modeling of ValRS predicts that the missense mutation lies in a highly conserved region and could alter side chain packing, thus affecting tRNA binding or destabilizing the interface between the catalytic and tRNA binding domains. Further quantitation of the expression of VARS showed remarkably reduced levels of mRNA and protein in skin derived fibroblasts. Aminoacylation experiments on patient derived cells showed markedly reduced enzyme activity of ValRS suggesting the mutations to be loss of function. Bi-allelic mutations in cytoplasmic amino acyl tRNA synthetases are well-known for their role in neurodegenerative disorders, yet human disorders associated with VARS mutations have not yet been clinically well characterized. Our study describes the phenotype associated with recessive VARS mutations and further functional delineation of the pathogenicity of novel variants identified, which widens the clinical and genetic spectrum of patients with progressive microcephaly.



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Response to the Letter by Poddighe et al. regarding our manuscript “Basophils activated via TLR signaling may contribute to pathophysiology of type 1 autoimmune pancreatitis”



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The Effect of Total Hip Arthroplasty on Sports and Work Participation: A Systematic Review and Meta-Analysis

Abstract

Background

Total hip arthroplasty (THA) is a successful procedure to treat end-stage hip osteoarthritis. The procedure is increasingly performed in adults of working age, who often wish to return to sports (RTS) and return to work (RTW). However, a systematic overview of the evidence on RTS and RTW after THA is lacking.

Objectives

Our aim was to systematically review (1) the extent to which patients RTS and RTW after THA, including (2) the time to RTS and RTW.

Methods

We searched MEDLINE and Embase from inception until October 2017. Two authors screened and extracted the data, including study information, patient demographics, rehabilitation protocols and pre- and postoperative sports and work participation. Methodological quality was assessed using the Newcastle–Ottawa scale. Data on pre- and postoperative sports and work participation were pooled using descriptive statistics.

Results

A total of 37 studies were included, of which seven were prospective studies and 30 were retrospective studies. Methodological quality was high in 11 studies, moderate in 16 studies, and low in ten studies. RTS was reported in 14 studies. Mean RTS was 104% to the pre-surgery level and 82% to the pre-symptomatic sports level. Time to RTS varied from 16 to 28 weeks. RTW was reported in 23 studies; the mean was 69%. Time to RTW varied from 1 to 17 weeks.

Conclusion

A great majority of patients RTS and RTW after THA within a timeframe of 28 and 17 weeks, respectively. For the increasingly younger THA population, this is valuable information that can be used in the preoperative shared decision-making process.



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Structural variation in the 3D genome



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A Randomized Trial Comparing the Effect of Fiberoptic Selection and Guidance Versus Random Selection, Blind Insertion, and Direct Laryngoscopy, on the Incidence and Severity of Epistaxis After Nasotracheal Intubation.

A Randomized Trial Comparing the Effect of Fiberoptic Selection and Guidance Versus Random Selection, Blind Insertion, and Direct Laryngoscopy, on the Incidence and Severity of Epistaxis After Nasotracheal Intubation.

Anesth Analg. 2018 Apr 19;:

Authors: Tong JL, Tung A

Abstract
BACKGROUND: Epistaxis, or nasal bleeding, is a common complication after nasotracheal intubation (NTI). Because such bleeding is likely related to trauma during intubation, use of fiberoptic visualization and guidance rather than direct laryngoscopy may affect the incidence and severity of epistaxis. We compared the incidence of epistaxis after NTI using a fiberoptic versus a direct laryngoscopy approach.
METHODS: Seventy patients who were able to breathe easily through unobstructed nostrils and required NTI as part of their anesthetic management were recruited. Exclusion criteria included unequal nasal airflow, nostril obstruction, previous nasal trauma or surgery, and coagulation abnormalities as determined by history. Patients were randomly assigned to undergo NTI with thermosoftened Mallinckrodt nasal Ring-Adair-Elwyn (RAE) tubes via either traditional direct laryngoscopy using a Macintosh blade or fiberoptic nasal intubation. All patients first underwent anesthetic induction and were randomized to blind or fiberoptic groups. Patients in the blind insertion/direct laryngoscopy group were then intubated via a randomly selected nostril. Patients in the fiberoptic group underwent an asleep nasal fiberoptic examination to determine the most patent nostril, followed by tube insertion under fiberoptic guidance. Ten minutes after NTI, the incidence and severity of epistaxis were evaluated and graded by the surgeon, who was blinded to the intubation method.
RESULTS: Initial nasal fiberoptic endoscopy identified asymptomatic nasal pathology in 51% of patients: inferior turbinate hypertrophy (28.6%) and deviation of the nasal septum in (22.8%). The incidence of epistaxis was higher in the blind insertion/direct laryngoscopy group (88%) than in the fiberoptic group (51%; relative risk, 0.55; 95% confidence interval, 0.38-0.79; P = .0011). The severity of bleeding was also greater in the blind tube insertion/direct laryngoscopy cohort (Wilcoxon Mann-Whitney odds, 3.5; 95% confidence interval, 1.8-11.1).
CONCLUSIONS: Fiberoptic nostril selection and guidance during NTI reduced the incidence and severity of epistaxis when compared with NTI performed via blind insertion and direct laryngoscopy.

PMID: 29683824 [PubMed - as supplied by publisher]



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