bluuebunny/crossref_metadata_2025 huggingface dataset:
The Tigecycline Evaluation and Surveillance Trial; assessment of the activity of tigecycline and other selected antibiotics against Gram-positive and Gram-negative pathogens from France collected between 2004 and 2016
Authors: Decousser Jean-Winoc , Woerther Paul-Louis , Soussy Claude-James , Fines-Guyon Marguerite , Dowzicky Michael J.
Published: May 2018

Background

A high level of antibiotic consumption in France means antimicrobial resistance requires rigorous monitoring. The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) is a global surveillance study that monitors the in vitro activities of tigecycline and a panel of marketed antimicrobials against clinically important Gram-positive and Gram-negative isolates.

Methods

Annually clinically relevant strains were prospectively included in the survey through a national network of hospital-based laboratories. MICs were determined locally by broth microdilution using CLSI guidelines. Antimicrobial susceptibility was assessed using European Committee on Antimicrobial Susceptibility Testing breakpoints.

Results

Thirty-three centres in France collected 26,486 isolates between 2004 and 2016. Enterococcus species were highly susceptible (≥94.4%) to linezolid, tigecycline and vancomycin. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), were susceptible (≥99.9%) to tigecycline, vancomycin and linezolid. Between 2004 and 2016, 27.7% of S. aureus isolates were MRSA, decreasing from 28.0% in 2013 to 23.5% in 2016. Susceptibility of Streptococcus pneumoniae isolates was 100% to vancomycin, and > 99.0% to levofloxacin, linezolid and meropenem; 3.0% were penicillin-resistant S. pneumoniae (100% susceptibility to vancomycin and linezolid). Escherichia coli isolates were highly susceptible (> 98.0%) to meropenem, tigecycline and amikacin. The rate of extended-spectrum β-lactamase (ESBL) positive E. coli increased from 2004 (3.0%), but was stable from 2012 (23.1%) to 2016 (19.8%). Susceptibility of Klebsiella pneumoniae isolates was 99.4% to meropenem and 96.5% to amikacin. The proportion of ESBL-positive K. pneumoniae isolates increased from 2004 (7.5%) to 2012 (33.3%) and was highest in 2016 (43.6%). A. baumannii was susceptible to meropenem (81.0%) and amikacin (74.9%); none of the 6.2% of isolates identified as multidrug-resistant (MDR) was susceptible to any agents with breakpoints. P. aeruginosa isolates were most susceptible to amikacin (88.5%), and MDR rates were 13.6% in 2013 to 4.0% in 2016; susceptibility of MDR isolates was no higher than 31.4% to amikacin.

Conclusions

Rates of MRSA decreased slowly, while rates of ESBL-positive E. coli and K. pneumoniae increased from 2004 to 2016. Susceptibility of Gram-positive isolates to vancomycin, tigecycline, meropenem and linezolid was well conserved, as was susceptibility of Gram-negative isolates to tigecycline and meropenem. The spread of MDR non-fermentative isolates must be carefully monitored.
Fabrication and optimization of Nanodiamonds-composited poly(ε-caprolactone) fibrous matrices for potential regeneration of hard tissues
Authors: Ahn Guk Young , Ryu Tae-Kyung , Choi Yu Ri , Park Ju Ri , Lee Min Jeong , Choi Sung-Wook
Published: May 2018

Background

Electrospun fibrous matrices are of great importance for tissue engineering and drug delivery device. However, relatively low mechanical strength of the fibrous matrix is one of the major disadvantages. NDs with a positive charge were selected to enhance the mechanical property of a composited fibrous matrix by inducing the intermolecular interaction between NDs and polymer chain. We prepared ND-composited poly (ε-caprolactone) (PCL) fibrous matrices by electrospinning and evaluated their performance in terms of mechanical strength and cell behaviors.

Methods

A predetermined amounts of NDs (0.5, 1, 2 and 3 wt%) were added into PCL solution in a mixture of chloroform and 2,2,2-trifluoroethanol (8:2). ND-composited PCL (ND/PCL) fibrous matrices were prepared by electrospinning method. The tensile properties of the ND/PCL fibrous matrices were analyzed by using a universal testing machine. Mouse calvaria-derived preosteoblast (MC3T3-E1) was used for cell proliferation, alkaline phosphatase (ALP) assay, and Alizarin Red S staining.

Results

The diameters of the fibrous matrices were adjusted to approximately 1.8 μm by changing process variables. The intermolecular interaction between NDs and PCL polymers resulted in the increased tensile strength and the favorable interfacial adhesion in the ND/PCL fibrous matrices. The ND/PCL fibrous matrix with 1 wt% of ND had the highest tensile strength among the samples and also improved proliferation and differentiation of MC3T3-E1 cells.

Conclusions

Compared to the other samples, the ND/PCL fibrous matrix with 1 wt% of ND concentration exhibited superior performances for MC3T3 cells. The ND/PCL fibrous matrix can be potentially used for bone and dental tissue engineering.
Prestack imaging of seismic data using Lp iterative reweighted least-squares wavefield extrapolation filters in the frequency-space domain
Authors: Mousa Wail A.
Published: May 2018

A stable explicit depth wavefield extrapolation is obtained using [Formula: see text] iterative reweighted least-squares (IRLS) frequency-space ([Formula: see text]-[Formula: see text]) finite-impulse response digital filters. The problem of designing such filters to obtain stable images of challenging seismic data is formulated as an [Formula: see text] IRLS minimization. Prestack depth imaging of the challenging Marmousi model data set was then performed using the explicit depth wavefield extrapolation with the proposed [Formula: see text] IRLS-based algorithm. Considering the extrapolation filter design accuracy, the [Formula: see text] IRLS minimization method resulted in an image with higher quality when compared with the weighted least-squares method. The method can, therefore, be used to design high-accuracy extrapolation filters.
Alcohol use disorders in people with intellectual disability
Authors: Williams Fionnuala , Kouimtsidis Christos , Baldacchino Alexander
Published: May 2018

This article initially highlights that although the prevalence of alcohol use disorders in people with intellectual disability (PWID) appears to be low, it is a significant issue. This group can be more vulnerable to the adverse effects of alcohol and it is likely that many PWID who have alcohol use disorders are not being identified. We go on to review the limited existing literature on treatment for PWID who have alcohol use disorders and the challenges in meeting the needs of this patient group. We explore how assessment and treatment of alcohol use disorders in this population can be and needs to be tailored to the needs of PWID on an individual basis. There is also discussion about the use of incapacity legislation to treat this group.

LEARNING OBJECTIVES

•

Be aware that alcohol use disorders can be especially problematic for PWID, that such disorders can often go undetected and that adapted screening techniques may be needed to identify such problems

•

Understand the difficulties that this population has in accessing addiction services and that successful management of PWID who misuse alcohol is usually dependent on appropriate joint working between intellectual disability and addiction services

•

Be aware that PWID are not a homogeneous group, rather they vary widely in their abilities, necessitating interventions tailored to the individual, and that the use of compulsory measures to manage PWID who lack capacity regarding to their alcohol use should be done with caution

DECLARATION OF INTEREST

None.
Genetic Risk for Subsequent Neoplasms Among Long-Term Survivors of Childhood Cancer
Authors: Wang Zhaoming , Wilson Carmen L. , Easton John , Thrasher Andrew , Mulder Heather , Liu Qi , Hedges Dale J. , Wang Shuoguo , Rusch Michael C. , Edmonson Michael N. , Levy Shawn , Lanctot Jennifer Q. , Caron Eric , Shelton Kyla , Currie Kelsey , Lear Matthew , Patel Aman , Rosencrance Celeste , Shao Ying , Vadodaria Bhavin , Yergeau Donald , Sapkota Yadav , Brooke Russell J. , Moon Wonjong , Rampersaud Evadnie , Ma Xiaotu , Chang Ti-Cheng , Rice Stephen V. , Pepper Cynthia , Zhou Xin , Chen Xiang , Chen Wenan , Jones Angela , Boone Braden , Ehrhardt Matthew J. , Krasin Matthew J. , Howell Rebecca M. , Phillips Nicholas S. , Lewis Courtney , Srivastava Deokumar , Pui Ching-Hon , Kesserwan Chimene A. , Wu Gang , Nichols Kim E. , Downing James R. , Hudson Melissa M. , Yasui Yutaka , Robison Leslie L. , Zhang Jinghui
Published: May 2018

Purpose

Childhood cancer survivors are at increased risk of subsequent neoplasms (SNs), but the germline genetic contribution is largely unknown. We assessed the contribution of pathogenic/likely pathogenic (P/LP) mutations in cancer predisposition genes to their SN risk.

Patients and Methods

Whole-genome sequencing (30-fold) was performed on samples from childhood cancer survivors who were ≥ 5 years since initial cancer diagnosis and participants in the St Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical follow-up. Germline mutations in 60 genes known to be associated with autosomal dominant cancer predisposition syndromes with moderate to high penetrance were classified by their pathogenicity according to the American College of Medical Genetics and Genomics guidelines. Relative rates (RRs) and 95% CIs of SN occurrence by mutation status were estimated using multivariable piecewise exponential regression stratified by radiation exposure.

Results

Participants were 3,006 survivors (53% male; median age, 35.8 years [range, 7.1 to 69.8 years]; 56% received radiotherapy), 1,120 SNs were diagnosed among 439 survivors (14.6%), and 175 P/LP mutations were identified in 5.8% (95% CI, 5.0% to 6.7%) of survivors. Mutations were associated with significantly increased rates of breast cancer (RR, 13.9; 95% CI, 6.0 to 32.2) and sarcoma (RR, 10.6; 95% CI, 4.3 to 26.3) among irradiated survivors and with increased rates of developing any SN (RR, 4.7; 95% CI, 2.4 to 9.3), breast cancer (RR, 7.7; 95% CI, 2.4 to 24.4), nonmelanoma skin cancer (RR, 11.0; 95% CI, 2.9 to 41.4), and two or more histologically distinct SNs (RR, 18.6; 95% CI, 3.5 to 99.3) among nonirradiated survivors.

Conclusion

The findings support referral of all survivors for genetic counseling for potential clinical genetic testing, which should be prioritized for nonirradiated survivors with any SN and for those with breast cancer or sarcoma in the field of prior irradiation.
Automated Assessment of Existing Patient’s Revised Cardiac Risk Index Using Algorithmic Software
Authors: Hofer Ira S. , Cheng Drew , Grogan Tristan , Fujimoto Yohei , Yamada Takashige , Beck Lauren , Cannesson Maxime , Mahajan Aman
Published: May 2018

BACKGROUND:

Previous work in the field of medical informatics has shown that rules-based algorithms can be created to identify patients with various medical conditions; however, these techniques have not been compared to actual clinician notes nor has the ability to predict complications been tested. We hypothesize that a rules-based algorithm can successfully identify patients with the diseases in the Revised Cardiac Risk Index (RCRI).

METHODS:

Patients undergoing surgery at the University of California, Los Angeles Health System between April 1, 2013 and July 1, 2016 and who had at least 2 previous office visits were included. For each disease in the RCRI except renal failure—congestive heart failure, ischemic heart disease, cerebrovascular disease, and diabetes mellitus—diagnosis algorithms were created based on diagnostic and standard clinical treatment criteria. For each disease state, the prevalence of the disease as determined by the algorithm, International Classification of Disease (ICD) code, and anesthesiologist’s preoperative note were determined. Additionally, 400 American Society of Anesthesiologists classes III and IV cases were randomly chosen for manual review by an anesthesiologist. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve were determined using the manual review as a gold standard. Last, the ability of the RCRI as calculated by each of the methods to predict in-hospital mortality was determined, and the time necessary to run the algorithms was calculated.

RESULTS:

A total of 64,151 patients met inclusion criteria for the study. In general, the incidence of definite or likely disease determined by the algorithms was higher than that detected by the anesthesiologist. Additionally, in all disease states, the prevalence of disease was always lowest for the ICD codes, followed by the preoperative note, followed by the algorithms. In the subset of patients for whom the records were manually reviewed, the algorithms were generally the most sensitive and the ICD codes the most specific. When computing the modified RCRI using each of the methods, the modified RCRI from the algorithms predicted in-hospital mortality with an area under the receiver operating characteristic curve of 0.70 (0.67–0.73), which compared to 0.70 (0.67–0.72) for ICD codes and 0.64 (0.61–0.67) for the preoperative note. On average, the algorithms took 12.64 ± 1.20 minutes to run on 1.4 million patients.

CONCLUSIONS:

Rules-based algorithms for disease in the RCRI can be created that perform with a similar discriminative ability as compared to physician notes and ICD codes but with significantly increased economies of scale.
Efficacy of Malignant Hyperthermia Association of the United States–Recommended Methods of Preparation for Malignant Hyperthermia-Susceptible Patients Using Dräger Zeus Anesthesia Workstations and Associated Costs
Authors: Neira Victor Manuel , Al Madhoun Waleed , Ghaffari Kamyar , Barrowman Nicholas , Berrigan Patrick , Splinter William
Published: May 2018

BACKGROUND:

The objective of this study was to assess the efficacy and cost of Malignant Hyperthermia Association of the United States–recommended methods for preparing Dräger Zeus anesthesia workstations (AWSs) for the malignant hyperthermia-susceptible patient.

METHODS:

We studied washout profiles of sevoflurane, isoflurane, and desflurane in 3 Zeus AWS following 3 preparation methods. AWS was primed with 1.2 minimum alveolar concentration anesthetic for 2 hours using 2 L/min fresh gas flow, 500 mL tidal volume, and 12/min respiratory rate. Two phases of washout were performed: high flow (10 L/min) until anesthetic concentration was <5 parts per million (ppm) for 20 minutes and then low flow (3 L/min) for 20 minutes to identify the rebound effect. Preparation methods are as follows: method 1 (M1), changing disposables (breathing circuit, soda lime, CO2 line, and water traps); method 2 (M2), M1 plus replacing the breathing system with an autoclaved one; and method 3 (M3), M1 plus mounting 2 activated charcoal filters on respiratory limbs. Primary outcomes are as follows: time to obtain anesthetic concentration <5 ppm in the high-flow phase, peak anesthetic concentrations in the low-flow phase, and for M3 only, peak anesthetic concentration after 70 minutes of low-flow phase, when activated charcoal filters are removed. Secondary outcomes are as follows: cost analysis of time and resources to obtain anesthetic concentration <5 ppm in each method and a vapor-free Zeus AWS. Sensitivity analyses were performed using alternative assumptions regarding the costs and the malignant hyperthermia-susceptible caseload per year.

RESULTS:

Primary outcomes were as follows: M3 instantaneously decreased anesthetic concentration to <1 ppm with minimal impact of low-flow phase. M1 (median, 88 minutes; 95% confidence interval [CI], 69–112 minutes) was greater than M2 (median, 11 minutes; 95% CI, 9–15 minutes). Means of peak rebound anesthetic concentrations in M1, M2, and M3 were 15, 6, and 1 ppm, respectively (P < .001). Anesthetic concentration increased 33-fold (95% CI, 21–50) after removing charcoal filters (from 0.7 to 20 ppm). The choice of anesthetic agents did not impact the results. Secondary outcomes were as follows: M3 was the lowest cost when the cost of lost operating room (OR) time due to washout was included, and M1 was the lowest cost when it was not included. When the cost of lost OR time due to washout was considered the estimated cost/case of M3 was US $360 (M1, US $2670; M2, US $969; and a “vapor-free” Zeus AWS was US $930). The OR time and equipment costs represent the largest differentiators among the methods.

CONCLUSIONS:

Institutions in which demand for OR time has exceeded capacity should consider M3, and institutions with surplus OR capacity should consider M1.
The Effect of Labor Epidural Analgesia on Breastfeeding Outcomes: A Prospective Observational Cohort Study in a Mixed-Parity Cohort
Authors: Orbach-Zinger Sharon , Landau Ruth , Davis Atara , Oved Oren , Caspi Liron , Fireman Shlomo , Fein Shai , Ioscovich Alexander , Bracco Danielle , Hoshen Moshe , Eidelman Leonid A.
Published: May 2018

BACKGROUND:

The effect of labor epidural analgesia (LEA) on successful breastfeeding has been evaluated in several studies with divergent results. We hypothesized that LEA would not influence breastfeeding status 6 weeks postpartum in women who intended to breastfeed in an environment that encourages breastfeeding.

METHODS:

In this prospective observational cohort study, a total of 1204 women intending to breastfeed, delivering vaginally with or without LEA, were included; breastfeeding was recorded at 3 days and 6 weeks postpartum. Primary outcome was breastfeeding at 6 weeks, and the χ2 test was used for comparisons between women delivering with and without LEA, according to parity status and previous breastfeeding experience. Total epidural fentanyl dose and oxytocin use (yes/no) were recorded. A multivariable logistic regression was performed to assess factors affecting breastfeeding at 6 weeks.

RESULTS:

The overall breastfeeding rate at 6 weeks was 76.9%; it was significantly lower among women delivering with LEA (74.0%) compared with women delivering without LEA (83.4%; P < .001). Among 398 nulliparous women, 84.9% delivered with LEA, compared with 61.8% of multiparous women (P < .001). Multiparous women (N = 806) were more likely to breastfeed at 6 weeks (80.0% vs 70.6% nullipara; P < .001). Using multivariable logistic regression that accounted for 14 covariates including parity, and an interaction term between parity and LEA use, LEA was significantly associated with reduced breastfeeding at 6 weeks (odds ratio, 0.60; 95% confidence interval, 0.40–0.90; P = .015). In a modified multivariable logistic regression where parity was replaced with previous breastfeeding experience, both as a covariate and in the interaction term, only previous breastfeeding experience was associated with increased breastfeeding at 6 weeks (odds ratio, 3.17; 95% confidence interval, 1.72–5.80; P < .001).

CONCLUSIONS:

In our mixed-parity cohort, delivering with LEA was associated with reduced likelihood of breastfeeding at 6 weeks. However, integrating women’s previous breastfeeding experience, the breastfeeding rate was not different between women delivering with and without LEA among the subset of multiparous women with previous breastfeeding experience. Therefore, our findings suggest that offering lactation support to the subset of women with no previous breastfeeding experience may be a simple approach to improve breastfeeding success. This concept subscribes to the notion that women at risk for an undesired outcome be offered tailored interventions with a personalized approach.
Opioid Use Disorders: Perioperative Management of a Special Population
Authors: Ward Emine Nalan , Quaye Aurora Naa-Afoley , Wilens Timothy E.
Published: May 2018

Opioid-related overdose deaths have reached epidemic levels within the last decade. The efforts to prevent, identify, and treat opioid use disorders (OUDs) mostly focus on the outpatient setting. Despite their frequent overrepresentation, less is known about the inpatient management of patients with OUDs. Specifically, the perioperative phase is a very vulnerable time for patients with OUDs, and little has been studied on the optimal management of acute pain in these patients. The preoperative evaluation should aim to identify those with OUDs and assess factors that may interfere with OUD treatment and pain management. Efforts should be made to provide education and assistance to patients and their support systems. For those who are actively struggling with opioid use, the perioperative phase can be an opportunity for engagement and to initiate treatment. Buprenorphine, methadone, and naltrexone medication treatment for OUD and opioid tolerance complicate perioperative pain management. A multidisciplinary team approach is crucial to provide clinically balanced pain relief without jeopardizing the patient’s recovery. This article reviews the existing literature on the perioperative management of patients with OUDs and provides clinical suggestions for the optimal care of this patient population.
Lateral line placodes of aquatic vertebrates are evolutionarily conserved in mammals
Authors: Washausen Stefan , Knabe Wolfgang
Published: May 2018

Placodes are focal thickenings of the surface ectoderm which, together with neural crest, generate the peripheral nervous system of the vertebrate head. Here we examine how, in embryonic mice, apoptosis contributes to the remodelling of the primordial posterior placodal area (PPA) into physically separated otic and epibranchial placodes. Using pharmacological inhibition of apoptosis-associated caspases, we find evidence that apoptosis eliminates hitherto undiscovered rudiments of the lateral line sensory system which, in fish and aquatic amphibia, serves to detect movements, pressure changes or electric fields in the surrounding water. Our results refute the evolutionary theory, valid for more than a century, that the whole lateral line was completely lost in amniotes. Instead, those parts of the PPA which, under experimental conditions, escape apoptosis have retained the developmental potential to produce lateral line placodes and the primordia of neuromasts that represent the major functional units of the mechanosensory lateral line system.
A two-phase response of endothelial cells to hydrostatic pressure
Authors: Prystopiuk Valeria , Fels Benedikt , Simon Caroline Sophie , Liashkovich Ivan , Pasrednik Dzmitry , Kronlage Cornelius , Wedlich-Söldner Roland , Oberleithner Hans , Fels Johannes
Published: May 2018

The vascular endothelium is exposed to three types of mechanical forces: blood flow-mediated shear stress, vessel diameter-dependent wall tension and hydrostatic pressure. Despite considerable variations of blood pressure during normal and pathological physiology, little is known about the acute molecular and cellular effects of hydrostatic pressure on endothelial cells. Here, we used a combination of quantitative fluorescence microscopy, atomic force microscopy and molecular perturbations to characterize the specific response of endothelial cells to application of pressure. We identified a two-phase response of endothelial cells with an initial response to acute (1 h) application of pressure (100 mmHg) followed by a different response to chronic (24 h) application. While both regimes induce cortical stiffening, the acute response is linked to Ca2+-mediated myosin activation, whereas the chronic cell response is dominated by increased cortical actin density and a loss in endothelial barrier function. GsMTx-4 and amiloride inhibit the acute pressure response, which suggests that the ENaC Na+ channel is a key player in endothelial pressure sensing. The described two-phase pressure response may participate in the differential effects of transient changes in blood pressure and hypertension.
A genome-wide RNAi screen identifies MASK as a positive regulator of cytokine receptor stability
Authors: Fisher Katherine H. , Fragiadaki Maria , Pugazhendhi Dhamayanthi , Bausek Nina , Arredondo Maria A. , Thomas Sally J. , Brown Stephen , Zeidler Martin P.
Published: May 2018

Cytokine receptors often act via the Janus kinase and signal transducer and activator of transcription (JAK/STAT) pathway to form a signalling cascade that is essential for processes such as haematopoiesis, immune responses and tissue homeostasis. In order to transduce ligand activation, cytokine receptors must dimerise. However, mechanisms regulating their dimerisation are poorly understood. In order to better understand the processes regulating cytokine receptor levels, and their activity and dimerisation, we analysed the highly conserved JAK/STAT pathway in Drosophila, which acts via a single receptor, known as Domeless. We performed a genome-wide RNAi screen in Drosophila cells, identifying MASK as a positive regulator of Domeless dimerisation and protein levels. We show that MASK is able to regulate receptor levels and JAK/STAT signalling both in vitro and in vivo. We also show that its human homologue, ANKHD1, is also able to regulate JAK/STAT signalling and the levels of a subset of pathway receptors in human cells. Taken together, our results identify MASK as a novel regulator of cytokine receptor levels, and suggest functional conservation, which may have implications for human health.

This article has an associated First Person interview with the first author of the paper.
Successful CRISPR/Cas9 mediated homologous recombination in a chicken cell line
Authors: Antonova Ekaterina , Glazova Olga , Gaponova Anna , Eremyan Aykaz , Zvereva Svetlana , Grebenkina Natalya , Volkova Natalya , Volchkov Pavel
Published: May 2018

Background: CRISPR/Cas9 system is becoming the dominant genome editing tool in a variety of organisms. CRISPR/Cas9 mediated knock out has been demonstrated both in chicken cell lines and in chicken germ cells that served to generate genetically modified birds. However, there is limited data about CRISPR/Cas9 dependent homology directed repair (HDR) for avian, even in cell culture. Few attempts have been made with integrations in safe harbor loci of chicken genome that induces constitutive expression of the inserted gene. Gene expression under an endogenous promoter would be more valuable than under a constitutive exogenous promoter, as it allows the gene expression to be tissue-specific.

Methods: Three gRNAs were chosen to target chicken 3’-untranslated region of GAPDH gene. Cas9-mediated activity in the targeted locus for the gRNAs in DF-1 cells was estimated by T7E1 assay. To edit the locus, the HDR cassette was added along with CRISPR/Cas9. The inserted sequence contained eGFP in frame with a GAPDH coding sequence via P2A and Neomycin resistance gene (neoR) under cytomegalovirus promoter. Correct integration of the cassette was confirmed with fluorescent microscopy, PCR analysis and sequencing. Enrichment of modified cells was done by G418 selection. Efficiency of integration was assessed with fluorescence activated cell sorting (FACS).

Results: We have established a CRISPR/Cas9 system to target an endogenous locus and precisely insert a gene under endogenous control. In our system, we used positive and negative selection to enrich modified cells and remove cells with undesirable insertions. The efficiency of CRISPR/Cas9-mediated HDR was increased up to 90% via G418 enrichment. We have successfully inserted eGFP under control of the chicken GAPDH promoter.

Conclusions: The approach can be used further to insert genes of interest under control of tissue-specific promoters in primordial germ cells in order to produce genetically modified birds with useful for biotechnological purposes features.
Enhancer functions in three dimensions: beyond the flat world perspective
Authors: Göndör Anita , Ohlsson Rolf
Published: May 2018

Transcriptional enhancers constitute a subclass of regulatory elements that facilitate transcription. Such regions are generally organized by short stretches of DNA enriched in transcription factor-binding sites but also can include very large regions containing clusters of enhancers, termed super-enhancers. These regions increase the probability or the rate (or both) of transcription generally in cis and sometimes over very long distances by altering chromatin states and the activity of Pol II machinery at promoters. Although enhancers were discovered almost four decades ago, their inner workings remain enigmatic. One important opening into the underlying principle has been provided by observations that enhancers make physical contacts with their target promoters to facilitate the loading of the RNA polymerase complex. However, very little is known about how such chromatin loops are regulated and how they govern transcription in the three-dimensional context of the nuclear architecture. Here, we present current themes of how enhancers may boost gene expression in three dimensions and we identify currently unresolved key questions.
New targets for resolution of airway remodeling in obstructive lung diseases
Authors: Nayak Ajay P. , Deshpande Deepak A. , Penn Raymond B.
Published: May 2018

Airway remodeling (AR) is a progressive pathological feature of the obstructive lung diseases, including asthma and chronic obstructive pulmonary disease (COPD). The pathology manifests itself in the form of significant, progressive, and (to date) seemingly irreversible changes to distinct respiratory structural compartments. Consequently, AR correlates with disease severity and the gradual decline in pulmonary function associated with asthma and COPD. Although current asthma/COPD drugs manage airway contraction and inflammation, none of these effectively prevent or reverse features of AR. In this review, we provide a brief overview of the features and putative mechanisms affecting AR. We further discuss recently proposed strategies with promise for deterring or treating AR.
Chemical crosslinking analysis of β-dystroglycan in dystrophin-deficient skeletal muscle
Authors: Murphy Sandra , Zweyer Margit , Mundegar Rustam R. , Swandulla Dieter , Ohlendieck Kay
Published: May 2018

Background: In Duchenne muscular dystrophy, primary abnormalities in the membrane cytoskeletal protein dystrophin trigger the loss of sarcolemmal linkage between the extracellular matrix component laminin-211 and the intracellular cortical actin membrane cytoskeleton. The disintegration of the dystrophin-associated glycoprotein complex renders the plasma membrane of contractile fibres more susceptible to micro-rupturing, which is associated with abnormal calcium handling and impaired cellular signalling in dystrophinopathy.

Methods: The oligomerisation pattern of β-dystroglycan, an integral membrane protein belonging to the core dystrophin complex, was studied using immunoprecipitation and chemical crosslinking analysis. A homo-bifunctional and non-cleavable agent with water-soluble and amine-reactive properties was employed to study protein oligomerisation in normal versus dystrophin-deficient skeletal muscles. Crosslinker-induced protein oligomerisation was determined by a combination of gel-shift analysis and immunoblotting.

Results: Although proteomics was successfully applied for the identification of dystroglycan as a key component of the dystrophin-associated glycoprotein complex in the muscle membrane fraction, mass spectrometric analysis did not efficiently recognize this relatively low-abundance protein after immunoprecipitation or chemical crosslinking. As an alternative approach, comparative immunoblotting was used to evaluate the effects of chemical crosslinking. Antibody decoration of the crosslinked microsomal protein fraction from wild type versus the mdx-4cv mouse model of dystrophinopathy revealed oligomers that contain β-dystroglycan. The protein exhibited a comparable reduction in gel electrophoretic mobility in both normal and dystrophic samples. The membrane repair proteins dysferlin and myoferlin, which are essential components of fibre regeneration and counteract the dystrophic phenotype, were also shown to exist in high-molecular mass complexes.

Conclusions: The muscular dystrophy-related reduction in the concentration of β-dystroglycan, which forms in conjunction with its extracellular binding partner α-dystroglycan a critical plasmalemmal receptor for laminin-211, does not appear to alter its oligomeric status. Thus, independent of direct interactions with dystrophin, this sarcolemmal glycoprotein appears to exist in a supramolecular assembly in muscle.
FUT2 secretor genotype and susceptibility to infections and chronic conditions in the ALSPAC cohort
Authors: Azad Meghan B. , Wade Kaitlin H. , Timpson Nicholas J.
Published: May 2018

Background: The FUT2 (fucosyltransferase 2) gene encodes alpha (1,2) fucosyltransferase, which determines blood group secretor status. Being homozygous for the inactive “non-secretor” rs601338(A) allele appears to confer resistance to certain infections (e.g. Norovirus, Rotavirus and Helicobacter pylori) and susceptibility to others (e.g. Haemophilus influenza and Streptococcus pneumonia). Non-secretors also have an increased risk of type 1 diabetes and inflammatory bowel disease. We aimed to determine the association of the FUT2 secretor genotype with infections and chronic conditions in the population-based Avon Longitudinal Study of Parents and Children (ALSPAC).

Methods: This study included 7,582 pregnant women from the ALSPAC pregnancy cohort. Personal history of infections (measles, mumps, chicken pox, whooping cough, cold sores, meningitis, genital herpes, gonorrhea and urinary infections) and chronic conditions (kidney disease, hypertension, diabetes, rheumatism, arthritis, psoriasis, hay fever, asthma, eczema and various allergies) were self-reported by standardized questionnaire. FUT2 secretor status was determined from the rs601338 genotype.

Results: Overall, 1920 women (25.3%) were homozygous for the FUT2 non-secretor allele (AA). Secretor status was associated with mumps, with 68% of non-secretors experiencing this infection, compared to 48% of secretors (RR, 1.40; 95% CI, 1.34–1.46; p<0.0001). A weaker association was observed for measles infection (76% vs. 72%; RR, 1.05; 95% CI, 1.02–1.09; p=0.0008). Non-secretors also experienced a 39% increased risk of kidney disease (5.4% vs. 3.9%; RR, 1.39; 95% CI, 1.11–1.75; p=0.004). For some conditions, including gonorrhea and arthritis, FUT2 heterozygosity (GA) appeared to confer an intermediate phenotype. There was no strong evidence of association between FUT2 secretor status and other infections or chronic conditions, although statistical power was limited for rare outcomes.

Conclusion: Our results identify an association between FUT2 secretor status and kidney disease, and confirm a recently reported association with susceptibility to mumps infection. The clinical implications of these associations warrant further investigation.
Specificity of cultural interpretation: from theory to practice
Authors: Симбирцева Наталья , Simbirceva Natal'ya
Published: May 2018

The monograph is devoted to the cultural interpretation of the text of culture: approaches to its definition are indicated, the codes of culture in the historical and cultural context are considered, the importance of visual as a special way of "grasping" reality in historical retrospect and in the conditions of modern reality is revealed.
The ideal types of the reader are described: Flanker, reader-interpreter, critic, actualizing mechanisms of reading texts of any modification.
The author offers the analysis of content and functional features of existence of the text of culture, cultural texts (practices) and separate artifacts at the turn of the XX-XXI centuries; the possibilities of formation of critical thinking in the conditions of media culture are revealed.
Prevention versus Clinical Management of Suicide Attempts in Adolescents: What are the Costs?
Authors: Ortegón Monroy Mónica María , Martínez Céspedes Ángela , Pérez Olmos Isabel
Published: May 2018

Introduction: Suicide is a worldwide public health problem, and being the youth are among one of the most affected population groups. In Colombia there is no evidence available about the cost of suicide care or prevention. Or attention to those who make suicide attempts assistance or prevention of suicide. This type of analysis is necessary to guide decisions about resource distribution in mental health and to reduce suicideal rates amongst youths in our country. Thus, the purpose of this study is to estimate and compare the mean cost of in-patient care cost treatment cost of youth suicidal youth suicide attempts, with the mean cost of participation in a school-based suicide preventive prevention program in for adolescents. Materials and methods: Medical charts of adolescents hospitalized for suicideal attempts were reviewed, along with as well as registries from adolescent participants in a suicide preventive program in Bogotá in 2010. Resources used were identified and tariff costs were quantified. Results: The average in-patients cost of a teenage suicideal attempt was $1 814 000 Colombian pesos (cop) (n = 39) Colombian pesos, and of $10 307 000 cop (n = 5) Colombian pesos when intensive care was required. The average cost of participation in a prevention ve program was $113 000 cop (n = 24) Colombian pesos per high-risk teenager and of $47 000 cop (n = 101) Colombian pesos for teenagers without suicide such risk. Conclusion: With For the average in- patient cost of one suicidal suicide attempt, 16 high-risk teenagers could be enrolled in a suicide preventive prevention program.
Prevalencia de desórdenes músculo esqueléticos en trabajadores de una empresa de comercio de productos farmacéuticos
Authors: Sánchez Medina Andrés Felipe
Published: May 2018

Introducción: los desórdenes músculo esqueléticos (DME) tienen origen multifactorial. En Colombia corresponden al principal grupo diagnóstico en procesos relacionados con la determinación de origen y pérdida de capacidad laboral. El objetivo es determinar la relación entre síntomas músculo esqueléticos y factores ocupacionales, sociodemográ cos y de carga física en trabajadores de una empresa de comercio de productos farmacéuticos en Bogotá, Colombia (2015). Materiales y métodos: estudio de corte transversal en 235 trabajadores. Se incluyeron variables sociodemográficas, ocupacionales, carga física y las relacionadas con los síntomas músculo esqueléticos. Se utilizó el cuestionario ERGOPAR. Para el análisis de las variables se utilizó la Prueba Exacta de Fisher, el Odds Ratio (OR) con el Intervalo de Confianza (IC) del 95%. Se realizó el análisis Multivariado con Regresión Logística Binaria. Resultados: la prevalencia de síntomas por segmento relacionados con dme fue de 79,2%, siendo más prevalente en cuello, hombros y columna dorsal (48,1%). Hubo asociación entre factores sociodemográ cos y ocupacionales. Se encontró una asociación entre síntomas en cuello, hombros y/o columna dorsal, columna lumbar, rodillas y pies con factores de carga física por fuerza, postura y movimiento. Conclusión: las posturas bípedas con y sin desplazamiento, inclinaciones de tronco y cabeza, transporte manual de cargas, sexo femenino, antigüedad en el cargo y edad están asociadas conjuntamente con el riesgo para presentar DME.
How Much Does it Cost to Train a Physician in Colombia?
Authors: Gil-Rojas Yaneth , Gil-Tamayo Sebastián , Mosos Juan David , Hernández Fabián , Castañeda-Cardona Camilo , Lasalvia Pieralessandro , Rosselli Diego
Published: May 2018

Introduction: The objective is to estimate the costs to society of training a doctor at either a public or a private university in Colombia. Materials and methods: Direct and indirect costs were estimated in 2016 Colombian pesos (average exchange rate 3,051 COP per US dollar), as was the return on investment, expressed as net present value (NPV), return on investment (ROI), and internal rate of return (IRR). The time required to recover the investment in studying medicine was also determined, and this was contrasted with the counterfactual of studying in another academic program. A discount rate of 12 % was used. A sensitivity analysis was performed with several alternative scenarios. Results: In the baseline scenario, the total cost of training a physician in Colombia is US $80,971.80 at a private university and US $54,971.79 at a public university (of which $14,436.57 is contributed by the State in the latter case). The time to return of investment is 3 years 6 months for study at a public university and 7 years 3 months for study at a public university. Applying discount rates of 5%, 7.5%, and 12%, studying medicine presents a higher return than that obtained by studying in another academic program. Conclusions: The cost of training a medical doctor in Colombia is 70 % higher than the cost of training other professionals, but returns are greater due to subsequent higher income. Net returns are higher for graduates of public universities because their initial investment is smaller and their incomes are similar.
Condiciones socio-habitacionales y morbilidad percibida de desplazados internos residentes en Viviendas de Interés Social en Turbo, Antioquia
Authors: Castaño-Pineda Yeferson , Atehortúa-Mira Sonia María , López-Arango Yolanda
Published: May 2018

Introducción: investigación cuyo objetivo fue explorar las condiciones sociales y habitacionales de las víctimas de desplazamiento forzado que residen en viviendas de interés social (VIS) y su relación con la morbilidad percibida por enfermedad diarreica aguda e infección respiratoria aguda. Materiales y métodos: componente cuantitativo de un estudio mixto realizado con población desplazada en Turbo, Antioquia. La información fue recolectada mediante encuesta y lista de chequeo aplicadas a una muestra representativa y aleatorizada de 196 viviendas. Los datos fueron analizados con técnicas estadísticas descriptivas, bivariadas y modelos multivariados de regresión binomial para razones de prevalencia (RP). Resultados y discusión: los niños menores de cinco años mostraron mayor probabilidad de presentar síntomas relacionados con infección respiratoria aguda (IRA) [RP 2,07; IC 95% 1,60-2,67] y enfermedad diarreica aguda (EDA) [RP 1,90; IC 95% 1,24-2,91]. La prevalencia de síntomas de ira fue superior en mujeres [RP 1,24; IC 95 % 1,05-1,47], en viviendas con dos o menos habitaciones para dormir [RP 1,42; IC 95% 1,05-1,91] y con pisos de tierra y arena [RP 1,42; IC 95% 1,23-2,29]. La prevalencia de síntomas de eda se duplicó en viviendas sin cocina separada [RP 2,34; IC 95% 1,34-4,07] y hogares que no usan detergentes o desinfectantes en el aseo doméstico [RP 2,11; IC 95% 1,38-3,22]. En las viviendas estudiadas, la población infantil es más propensa a tener síntomas relacionados con ira y eda, situaciones que pueden aumentar cuando hay deterioro en pisos, carencia de espacios exclusivos para cocinar y su cientes para dormir, y hábitos de higiene inadecuados.
Historia del concepto de dolor total y reflexiones sobre la humanización de la atención a pacientes terminales
Authors: López Sánchez Juan Rafael , Rivera-Largacha Silvia
Published: May 2018

Introducción: en este artículo se estudia el concepto de ‘dolor total’ con el objetivo de abrir una reflexión sobre los aportes teóricos y prácticos que esta categoría puede ofrecer en el cuidado de pacientes terminales, enfatizando en la necesidad de humanizar la atención, como modo de restituir la calidad de vida y la dignidad de los pacientes, sus familias y sus allegados, y como modo de dignificar y mejorar la calidad y las condiciones del trabajo de los profesionales clínicos que acompañan a este tipo de pacientes en su tránsito hacia la muerte. Desarrollo: a lo largo del artículo se analiza el proceso histórico y epistemológico del cual surge el término ‘dolor total’ como categoría que aporta herramientas teóricas que permiten orientar el diagnóstico y el abordaje terapéutico del dolor en las condiciones particulares propias de la enfermedad terminal. Conclusión: el concepto de ‘dolor total’ permite entender el proceso del final de la vida como una experiencia de enfermedad (disease), padecimiento (illness) y disfunción social (sickness) que comporta diferentes formas de sufrimiento que deben ser atendidas de manera integral. La atención integral significa que el profesional de la salud debe centrarse más en el paciente que en su patología, y ofrecerle una mejor calidad de vida y acompañamiento en el proceso de morir.
Efeito do treinamento físico em diabéticos tipo I: revisão sistemática de ensaios clínicos randomizados
Authors: Gomes Roselaine , Rech Cassiano , Sousa Clóvis
Published: May 2018

O exercício físico (EF) tem sido recomendado no controle da diabetes tipo 1 (DM1), porém, seus efeitos na hemoglobina glicosilada (HbA1c), dose de insulina e perfil lipídico, ainda são controversos. O objetivo deste estudo foi analisar as evidências do EF em adolescentes com DM1, por meio de uma revisão sistemática. Realizou-se uma busca nas bases de periódicos PubMed, Biblioteca Virtual de Saúde e EBSCOHost. Foram incluídos estudos clínicos controlados e randomizados que testaram o efeito do EF na HbA1c, na dose de insulina e em marcadores do perfil lipídico em adolescentes com DM1, publicados em português ou inglês, entre 2000 e 2017. Foram incluídos cinco estudos em jovens de 10 a 16 anos. As intervenções foram com exercícios aeróbicos, exercícios combinados e pilates, em períodos de três a seis meses. A frequência foi uma a três vezes/semana, com sessões de 45 a 120 minutos e intensidades entre 40-85% da frequência cardíaca máxima (FCMáx), 80-90% da frequência cardíaca de reserva e 50-100% de 10 repetições máximas (RM). Apenas um estudo mostrou-se e caz na melhora da HbA1c, dois na dose de insulina e quatro no perfil lipídico. Um estudo foi efetivo na HbA1c, na dose de insulina e no perfil lipídico simultaneamente, incluindo exercícios aeróbicos, de flexibilidade, neuromusculares e de equilíbrio, com intensidade de 65-85% FCMáx e 50-100% de 10 RM. Os resultados apontam que não existe consistência nos achados. Conclui-se que não há evidência científica suficiente e consistente do tipo, frequência, intensidade e duração dos programas de EF para adolescentes com DM1.
Publications scenario about Family Health Support Centers
Authors: Seus Thamires , Freitas Matheus , Siqueira Fernando
Published: May 2018

A systematic review about publications on the Family Health Support Centers (FHSC) and the participation of the Physical Education Professional (PEP) was conducted. Recorded in PROS- PERO, following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) in Pubmed, Lilacs, Scopus, Bireme and SciELO, with the following keywords: Family Health Support Center; FHSC; Primary Health Care; Health Promotion; In- tervention Studies; Physical Education; Physical Activity. Sixty studies about NASF were found, most of them about the implementation of the program and about actions undertaken by the teams. Of the total, seven studies in the area of Physical Education. In conclusion, studies about FHSC are qualitative methods and do not address the e ectiveness of the developed actions, only describe them. As well as with publications about PEP.