bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum S-100 Protein, Relationship to Clinical Outcome in Acute Stroke
Authors: Abraha Hagosa D , Butterworth Richard J , Bath Philip M W , Wassif Wassif S , Garthwaite John , Sherwood Roy A
Published: February 2014

The clinical significance of serum S-100 protein, a protein released by damaged brain tissue, was assessed in patients with acute ischaemic or haemorrhagic stroke and matched controls. Serum S-100 protein concentration was significantly elevated in patients with ischaemic stroke [median (SQR): 0·27 (0·09) μg/L, n = 68] and haemorrhagic stroke [0·43 (0·23) μg/L, n = 13] compared to controls [0·11 (0·03) μg/L, n = 51, P<0·0001]. Although patients with haemorrhagic stroke had higher serum S-100 concentrations compared to patients with ischaemic stroke, this was not quite statistically significant. Serum S-100 concentrations were related to infarct size, large (total anterior circulation) infarcts concentrations having the highest [0·40 (0·22) μg/L], and small vessel (‘lacunar’) infarcts concentrations having the lowest [0·20 (0·06) μg/L, P<0·0005] concentrations. S-100 protein concentration was also significantly related to clinical outcome at three months measured using three disability and handicap scales ( n = 81): modified Barthel index ( rs=–0·285, P = 0·01), modified Rankin score ( rs = 0·313, P = 0·004) and Lindley score ( rs = 0·262, P = 0·018) with high values associated with poor clinical outcome. Similarly high values of serum S-100 protein were observed in patients who died or were discharged to an institution [median (SQR): 0·63 (0·29) μg/L and 0·37 (0·13) μg/L, respectively] compared to those who were discharged home [0·26 (0·11) μg/L, P = 0·13]. The present study suggests measurement of serum S-100 protein could be a useful prognostic marker of clinical outcome in acute stroke. Whether S-100 concentrations can be altered by therapeutic intervention in acute stroke remains to be elucidated. Indexing terms: acute stroke/serum S-100/Barthel index/Rankin scale.
The Postoperative Inflammatory Response to Injury following Laparoscopic Assisted Vaginal Hysterectomy versus Abdominal Hysterectomy
Authors: Labib M , Palfrey S , Paniagua E , Callender R
Published: February 2014

The magnitude of the inflammatory response to surgery depends on the degree of injury during surgical procedures. Laparoscopic techniques are generally associated with less postoperative pain and shorter hospital stay compared with open procedures, presumably due to less tissue injury and reduced inflammatory response. However, no study has been done, to our knowledge, to assess the inflammatory response to surgical trauma following laparoscopic assisted vaginal hysterectomy. We have, therefore, compared the magnitude of the inflammatory response to injury after laparoscopically assisted vaginal hysterectomy (11 patients) and abdominal hysterectomy (11 patients) by measuring serum C-reactive protein (CRP) and interleukin-6 (IL-6) on admission, and at 24 and 48 hours after the operation. Postoperatively, serum CRP rose significantly in both groups but levels in patients who underwent laparoscopically assisted vaginal hysterectomy were significantly lower than in those who underwent abdominal hysterectomy. Serum IL-6 rose significantly after abdominal hysterectomy but not after laparoscopically assisted vaginal hysterectomy. Our results show that the inflammatory response to surgical trauma was significantly less after laparoscopically assisted vaginal hysterectomy than after abdominal hysterectomy confirming that the laparoscopic procedure causes less tissue damage than the abdominal procedure.
Pleural Fluid Pseudouridine in Malignant and Benign Pleural Effusions
Authors: Mak T W L , Ho S S , Ho C S , Jones M G , Lai C K W , Lam C W K
Published: February 2014

Pseudouridine in urine and plasma has been proved to be a useful tumour marker in many malignant conditions. We studied its usefulness in pleural fluid for distinguishing malignant from non-malignant pleural effusions.

Pleural fluid pseudouridine concentrations in different groups of patients with pleural effusion (31 malignant, 29 benign, 16 unknown, 1 double pathology) was measured and compared. Its usefulness in distinguishing malignant from non-malignant pleural effusions was analysed by receiver-operating characteristic (ROC) curve analysis.

Pseudouridine concentrations in the malignant group were significantly higher than the non-malignant group ( P < 0.017, Bonferroni adjustment) with values overlapping extensively at the lower end. The area-under-the curve (AUC) value in the ROC curve analysis was 0.675 ( P < 0.05).

We conclude that the pleural fluid pseudouridine is of limited clinical value in distinguishing malignant from non-malignant pleural effusion due to its extensive overlap. However, it is useful when the concentration is higher than 65 μmol/L, which indicates malignancy.
Recommended Approaches for the Laboratory Measurement of Homocysteine in the Diagnosis and Monitoring of Patients with Hyperhomocysteinaemia
Authors: Moat S J , Bonham J R , Tanner M S , Allen J C , Powers H J
Published: February 2014

Several recent studies have indicated that an increased concentration of plasma homocysteine is an independent risk factor for the premature development of vascular disease. These important findings emphasize the need for careful selection of an appropriate analytical approach to diagnose and treat individuals who may be at risk. We compared the results obtained from the measurement of plasma total homocysteine (free + protein-bound fractions) by high-performance liquid chromatography (HPLC) with the measurement of plasma free homocystine (free fraction) by conventional ion-exchange chromatography in 10 patients with inherited defects of homocysteine metabolism and 13 obligate heterozygote individuals. This study can be used to formulate recommendations on the appropriate use of these assays in different clinical circumstances. Our results show that the concentration of total plasma homocysteine must exceed 60 μmol/L before plasma free homocystine becomes detectable by conventional ion-exchange chromatography. Similarly, assessment of the urinary excretion of homocysteine in these patients indicates that it may not become consistently detectable by conventional ion-exchange chromatography or HPLC until plasma total homocysteine exceeds 150 μmol/L.

On this basis, while most patients with classical homocystinuria would be detected by analysis of plasma using conventional ion-exchange chromatography or by measurement of of the urinary homocysteine excretion, occasional patients would be missed. When monitoring patients receiving treatment for classical homocystinuria, in whom metabolic control is good, and when investigating individuals with a suspected inherited defect of cobalamin or folate metabolism, a method which measures plasma total homocysteine should be used. The identification of moderate hyperhomocysteinaemia of undefined cause investigated in relation to a history of early vacsular disease can only be identified by this approach.
8DSS-Promoted Remineralization of Initial Enamel Caries In Vitro
Authors: Yang Y. , Lv X.P. , Shi W. , Li J.Y. , Li D.X. , Zhou X.D. , Zhang L.L.
Published: February 2014

Peptides containing 8 repeats of aspartate-serine-serine (8DSS) have been shown to promote the nucleation of calcium phosphate from solution into human enamel. Here we tested the ability of 8DSS to promote the remineralization of demineralized enamel in an in vitro model of artificial early enamel caries. Initial caries lesions were created in bovine enamel blocks, which were then subjected to 12 d of pH cycling in the presence of 25 µM 8DSS, 1 g/L NaF (positive control) or buffer alone (negative control). Absorption of 8DSS was verified by X-ray photoelectron spectroscopy. Mineral loss, lesion depth, and mineral content at the surface layer and at different depths of the lesion body were analyzed before and after pH cycling by polarized light microscopy and transverse microradiography. Mineral loss after pH cycling was significantly lower in the 8DSS samples than in the buffer-only samples, and lesions in the 8DSS samples were significantly less deep. Samples treated with 8DSS showed significantly higher mineral content than buffer-only samples in the region extending from the surface layer (30 µm) to the average lesion depth (110 µm). No significant differences were found between the samples treated with 8DSS and those treated with NaF. These findings suggest that 8DSS has the potential to promote remineralization of demineralized enamel.
Surface modification of aramid fibers by atmospheric pressure plasma-enhanced vapor deposition
Authors: Chu Yanyan , Chen Xiaogang , Sheel David W , Hodgkinson John L
Published: February 2014

Recent research results have indicated positive influences of inter-yarn friction on ballistic performance of woven fabrics and panels made from such fibers. The current investigation explores the effect of coating by means of atmospheric pressure plasma-enhanced vapor deposition with organic chemical (CH3)2Cl2Si on the inter-yarn friction. The scanning electron microscopy observations indicated that as the treatment time increases, more particles have been deposited on the surface of the fibers. The Fourier transform infrared spectra supported the existence of Si-O-Si vibration, which can be attributed to the chemical deposition. Energy-dispersive X-ray analysis further supported the deposition of the chemical compound. Experiments were carried out to evaluate the coefficients of static and kinetic frictions between the yarns and the results showed that the inter-yarn coefficient of static friction was increased from 0.1617 to 0.2969 and that of the kinetic friction increased from 0.1554 to 0.2436, as the treatment time increased to 4 minutes. In addition, there is evidence that the mechanical properties of the treated yarns were not negatively affected by the treatment.
Comparison of Tolerance and Cost‐Effectiveness of Two Nasal Anesthesia Techniques for Transnasal Flexible Laryngoscopy
Authors: Young VyVy N. , Smith Libby J. , Rosen Clark A.
Published: February 2014

Objective

(1) Compare tolerance of aerosolized spray versus syringe administration of topical anesthesia for transnasal flexible laryngoscopy (TFL), (2) analyze cost‐effectiveness of both techniques.

Study Design

Prospective, blinded, randomized trial.

Setting

Tertiary academic laryngology practice.

Methods

One hundred and eight patients underwent TFL over 3 months. Patients were randomized to receive equivalent dose 1:1 neosynephrine/4% plain lidocaine mixture via aerosolized spray (“spray”) or application with 1‐cc syringe (“syringe”). Patients and physicians independently rated comfort of TFL on 5‐point scale (1 = not at all comfortable to 5 = very comfortable). Data were collected on patient and endoscopist experience with TFL and reasons for poor tolerance of laryngoscopy. Cost analyses of disposable spray tips and syringes were calculated.

Results

Both patients and physicians reported very high tolerance of TFL. Patient tolerance appears to be similar between spray‐ versus syringe‐administered anesthesia, although study limitations preclude definitive analysis. Poor tolerance of laryngoscopy was reported in 6.5% with comparable distribution between anesthetic delivery methods. There was no impact of patient prior experience with TFL, and there was no difference between anesthetic methods for TFL performed by resident, fellow, or attending. The difference between costs of the disposable spray tip versus syringe was $1.32 per unit.

Conclusions

Use of a 1‐cc syringe is an effective method to provide topical nasal anesthesia for TFL and saves $1.32 per unit compared to disposable spray tips. In our practice, transition to syringe‐administered nasal anesthesia is projected to save $1300 per 1000 patients, or an anticipated $1000 per year per physician, with excellent patient tolerance of TFL.
Carbon Dioxide Laser Versus Stapler‐Assisted Endoscopic Zenker's Diverticulotomy: A Systematic Review and Meta‐Analysis
Authors: Parker Noah P. , Misono Stephanie
Published: February 2014

To evaluate outcomes following endoscopic management of Zenker's diverticula using a carbon dioxide laser (CO2) or stapler‐assisted technique, a systematic review and meta‐analysis were conducted. Seven retrospective, uncontrolled case series including 391 procedures met selection criteria. No higher quality studies were identified. Outcomes favoring the stapler technique included a shorter duration of nil per os (NPO) status (2 studies), length of hospitalization (LOH, 2 studies), and fewer postoperative fevers and abnormal chest x‐rays (1 study). Outcomes favoring the CO2 technique included greater improvement in postoperative dysphagia and regurgitation scores (2 studies) and a lower revision rate (1 study). Meta‐analysis demonstrated increased nondental complications in the CO2 group (odds ratio 3.81; 95% confidence interval, 1.37‐10.59; P =. 01) but no difference in duration of NPO (P =. 06), LOH (P =. 07), overall complications (P =. 08), dental complications (P =. 57), major complications (P =. 38), or revision surgery (P =. 82). Implications are limited by the quality of studies identified.
Costs of Outpatient Thyroid Surgery from the University HealthSystem Consortium (UHC) Database
Authors: Marino Matthew , Spencer Horace , Hohmann Sam , Bodenner Donald , Stack Brendan C.
Published: February 2014

Objective

To compare the cost of same‐day vs 23‐hour observation outpatient thyroidectomy at US academic medical centers.

Study Design

Cross‐sectional analysis of a national database.

Setting

The University HealthSystem Consortium (UHC) data collected from discharge summaries.

Subjects and Methods

Discharge data were collected from the first quarter of 2009 through the second quarter of 2013. The UHC database, compiled from more than 200 affiliated hospitals, was searched based on diagnosis codes for outpatient thyroid procedures. Cost data, calculated based on reported charges, were collected in addition to demographics. Comparisons were made between same‐day vs 23‐hour observation based on cost. Additional stratification was performed based on the extent of thyroidectomy.

Results

During the study period, 49,936 outpatient thyroidectomies were performed. Overnight observation (63%) was more common than same‐day discharge (37%). The overall mean cost of outpatient thyroidectomy was $5617, with a mean cost of same‐day surgery of $4642 compared with $6101 for overnight observation (P <. 0001). When stratifying by extent of thyroidectomy, the cost of same‐day surgery was consistently lower than that for overnight observation.

Conclusion

Outpatient thyroidectomy is commonly performed in the United States. It is most commonly performed on a 23‐hour overnight observation basis. Overnight stay and complications were chief among other factors associated with higher cost, independent of the type of thyroid procedure performed. In appropriately selected patients, same‐day thyroidectomy is a safe and cost‐effective alternative to overnight observation or inpatient thyroid procedures.
The importance of being a capable supplier: Italian industrial firms in global value chains
Authors: Agostino Mariarosaria , Giunta Anna , Nugent Jeffrey B. , Scalera Domenico , Trivieri Francesco
Published: February 2014

This article argues that joining global value chains may be decisive for supplier firms in developed countries by providing incentives and opportunities to upgrade their capabilities to export and innovate. We describe an investigation conducted on a sample of Italian manufacturing firms, drawn from a database spanning 1998–2006 that compares labour productivity and total factor productivity between supplier and final firms at the same level of demonstrated ability (measured in terms of exporting and innovating). Findings indicate that ‘traditional’ supplier firms are less productive than final firms; as the ability of supplier firms increases, their productivity shortfall decreases to the extent that for those able to both export and innovate, there is no statistically significant difference in productivity between supplier and final firms.
One-Step Repair for Cartilage Defects in a Rabbit Model
Authors: Dai Linghui , He Zhenming , Zhang Xin , Hu Xiaoqing , Yuan Lan , Qiang Ming , Zhu Jingxian , Shao Zhenxing , Zhou Chunyan , Ao Yingfang
Published: February 2014

Background:

Cartilage repair still presents a challenge to clinicians and researchers alike. A more effective, simpler procedure that can produce hyaline-like cartilage is needed for articular cartilage repair.

Hypothesis:

A technique combining microfracture with a biomaterial scaffold of perforated decalcified cortical-cancellous bone matrix (DCCBM; composed of cortical and cancellous parts) would create a 1-step procedure for hyaline-like cartilage repair.

Study Design:

Controlled laboratory study.

Methods:

For the in vitro portion of this study, mesenchymal stem cells (MSCs) were isolated from bone marrow aspirates of New Zealand White rabbits. Scanning electron microscopy (SEM), confocal microscopy, and 1,9-dimethylmethylene blue assay were used to assess the attachment, proliferation, and cartilage matrix production of MSCs grown on a DCCBM scaffold. For the in vivo experiment, full-thickness defects were produced in the articular cartilage of the trochlear groove of 45 New Zealand White rabbits, and the rabbits were then assigned to 1 of 3 treatment groups: perforated DCCBM combined with microfracture (DCCBM+M group), perforated DCCBM alone (DCCBM group), and microfracture alone (M group). Five rabbits in each group were sacrificed at 6, 12, or 24 weeks after the operation, and the repair tissues were analyzed by histological examination, assessment of matrix staining, SEM, and nanoindentation of biomechanical properties.

Results:

The DCCBM+M group showed hyaline-like articular cartilage repair, and the repair tissues appeared to have better matrix staining and revealed biomechanical properties close to those of the normal cartilage. Compared with the DCCBM+M group, there was unsatisfactory repair tissues with less matrix staining in the DCCBM group and no matrix staining in the M group, as well as poor integration with normal cartilage and poor biomechanical properties.

Conclusion:

The DCCBM scaffold is suitable for MSC growth and hyaline-like cartilage repair induction when combined with microfracture.

Clinical Relevance:

Microfracture combined with a DCCBM scaffold is a promising method that can be performed and adopted into clinical treatment for articular cartilage injuries.
Reason, power and history
Authors: Allen Amy
Published: February 2014

This paper re-examines the relationship between power, reason and history in Horkheimer and Adorno’s Dialectic of Enlightenment. Contesting Habermas’ highly influential reading of the text, I argue that Dialectic of Enlightenment, far from being a dead-end for critical theory, opens up important lines of thought in the philosophy of history that contemporary critical theorists would do well to recover. My focus is on the relationship that Horkheimer and Adorno trace between enlightenment rationality and the domination of inner and outer nature.
The future of critical theory between reason and power
Authors: Bankovsky Miriam
Published: February 2014

Amy Allen presents Adorno’s and Horkheimer’s Dialectic of Enlightenment as a productive movement between a commitment to the project of reason and a sensitivity to the effects on reason of power and domination. Agreeing with the thrust of her paper, my response considers two questions that Allen’s paper opens up. The first asks how individuals might seek emancipation through reason, knowing that their reason cannot transcend contexts of power. The second asks how best to practise critical theory, given that its analyses and categories cannot rid themselves of contexts of domination. To the first, I answer that Allen’s account of creative individual effort needs to be supplemented by the cultivation of an accommodating and welcoming culture, marked by the sorts of civic attitudes that Derrida and Habermas bring to their maturing relationship. Regarding the second, I extend Allen’s hopes for a post-Habermasian phase of critical theory, indicating four resources in contemporary French philosophy for its further development.
Enhancement of CRF-PEEK osseointegration by plasma-sprayed hydroxyapatite: A rabbit model
Authors: Suska Felicia , Omar Omar , Emanuelsson Lena , Taylor Mark , Gruner Philipp , Kinbrum Amy , Hunt Duncan , Hunt Trevor , Taylor Andy , Palmquist Anders
Published: February 2014

Carbon-fibre-reinforced polyether ether ketone (CFR-PEEK) exhibits excellent biomechanical properties as it has an elastic modulus similar to bone. However, CFR-PEEK displays inferior biocompatibility compared with titanium alloy and coating techniques are therefore of interest in order to improve integration. In this paper, the early biological response to CFR-PEEK implants, with and without hydroxyapatite coating, was investigated. Furthermore, a hydroxyapatite-coated titanium alloy reference served as a clinically relevant control. The study was conducted in a rabbit model, both in femur trabecular bone as well as in tibia cortical bone. The results demonstrated that an hydroxyapatite coating significantly enhances the bone response to PEEK implants in vivo. Moreover, in cortical bone, hydroxyapatite-coated PEEK implants induced superior bone response compared with hydroxyapatite-coated Ti ones. These results suggest that hydroxyapatite-coated CFR-PEEK is a suitable material for in vivo implantation.
Competitive regionalism and the territorial governance of uncertainty
Authors: Burroni Luigi
Published: February 2014

This article focuses on the model of local regulation of economic uncertainty that can be described as ‘ competitive regionalism’, a governance mode characterized by its own rhetoric, key actors and political economy. The first part of the article presents a contradiction: on the one hand, private actors and market regulation have gained much importance, but on the other this process of marketization has been partly balanced by the role played by local governments, collective actors and other bodies and organizations, although trade unions are playing only a weak role, especially where they do not have a local territorial base. Thus, marketization seems to increase rather than reduce the need for intervention by public actors and collective organizations able to reduce externalities produced by the market. The second part of the article shows the impact of the economic crisis on the model of competitive regionalism and a number of possible policy implications.
From opportunity to obligation: Medicalization of post-menopausal sexuality in Turkey
Authors: Erol Maral
Published: February 2014

In this article, I analyze the constructions of sexuality after menopause in the late 1990s and early 2000s, a period of increased medicalization of menopause in Turkey. I argue that the medicalization of menopause in Turkey contributed to framing sexual problems in middle age as the woman’s responsibility, offering hormone therapy as a solution and part of ‘maintenance work.’ Menopausal women’s sexuality is defined in relation to their partner’s sexuality in a monogamous marriage, and remaining sexually active is framed as a woman’s duty. These discussions contribute to understanding how medical authority is differently invoked in shaping middle-age sexuality in local contexts.
Moral reactions to reality TV: Television viewers’ endogenous and exogenous loci of morality
Authors: Scarborough Roscoe C , McCoy Charles Allan
Published: February 2014

Drawing upon a survey and 41 semi-structured interviews with television consumers, we examine the negative moral reactions that some people have to contemporary reality television. We explore the relationship between cultural preferences and moral condemnation. Television consumers who have a moral reaction to reality TV are more likely to be from a higher socio-economic position and are less likely to consume the genre. To more fully understand some viewers’ negative moral reactions to reality television, we examine the moral reasoning of television consumers. Moral reactions to reality TV can be classified as endogenous and exogenous. An endogenous focus is concerned with the immorality of consumption. An exogenous focus locates morality in cultural production. These moral positions are also socially patterned; television consumers with an exogenous locus of morality possess higher levels of cultural capital, greater education and are less likely to consume reality TV. Theoretically, we contend that cultural taste is being turned into moral condemnation. In other words, when cultural consumption is linked to moral position then a strong symbolic boundary can be formed that reinforces real-world boundaries amongst social groups. This condemnation serves to harden cultural, symbolic boundaries rooted in classed consumption practices.
Histone acetylation and expression of mono-aminergic transmitters synthetases involved in CUS-induced depressive rats
Authors: Liu Dan , Qiu Hong-Mei , Fei Hui-Zhi , Hu Xiao-Ya , Xia Hai-Jian , Wang Li-Jia , Qin Li-Juan , Jiang Xin-Hui , Zhou Qi-Xin
Published: February 2014

Histone acetylation has been linked to depression, the etiology of which involves many factors such as genetics, environments, and epigenetics. The aim of the present study was to investigate whether it was associated with epigenetic histone modification and gene expression of enzymes responsible for the biosynthesis of norepinephrine and serotonin in rat depression model induced by chronic unpredictable stress (CUS). Eight-week-old male Sprague-Dawley rats were exposed to CUS over 28 days. It was shown that the CUS-induced rats displayed remarked anxiety- and depression-like behavior with weakened locomotor activity in open field test and prolonged immobility in forced swimming test. Western blot revealed that CUS led to significant decrease in acetylation of H3 at Lysine 9 (K9) and H4 at Lysine 12 (K12) with obviously increasing histone deacetylases 5 (HDAC5) expression in hippocampus of CUS-induced rats. Meanwhile, there was an obviously decreased expression of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) both at protein and mRNA levels. Administration of sodium valproate (VPA), a histone deacetylase 5 (HDAC5) inhibitor, not only significantly relieved the anxiety- and depression-like behaviors of CUS-induced rats but also clearly blunted decrease of H3(K9) and H4(K12) acetylation and expression of TH and TPH, and prevented increase of HDAC5 expression. The results indicate that there exists possible interrelation between TH and TPH gene expression and epigenetic histone acetylation in CUS-induced depressive rats, which at least partly contributes to the etiology of depression.
Cultural Relevance in Urban Music Education
Authors: Doyle Jennifer Lee
Published: February 2014

Recent research indicates students of low socioeconomic status (SES) who participate in the arts have better social and academic outcomes than those who do not participate in arts instruction. Because many students in urban areas are from low SES, music instruction could be particularly beneficial. However, because of various factors, enrollment in music courses is very low in secondary schools; students of color and low SES are underrepresented. Equal access to music education for all students is important because arts education is essential for the creation of well-rounded, engaged citizens of the world. This synthesis of selected research literature examines the status of musical opportunities for students in urban areas and offers suggestions for creating greater equity and cultural relevance through music instruction.
Peptide inhibitors of C3 activation as a novel strategy of complement inhibition for the treatment of paroxysmal nocturnal hemoglobinuria
Authors: Risitano Antonio M. , Ricklin Daniel , Huang Yijun , Reis Edimara S. , Chen Hui , Ricci Patrizia , Lin Zhuoer , Pascariello Caterina , Raia Maddalena , Sica Michela , Del Vecchio Luigi , Pane Fabrizio , Lupu Florea , Notaro Rosario , Resuello Ranillo R. G. , DeAngelis Robert A. , Lambris John D.
Published: February 2014

Key Points

Peptidic C3 inhibitors of the compstatin family (Cp40) efficiently prevent hemolysis and opsonization of PNH erythrocytes in vitro. Pharmacokinetic studies show that sustained therapeutic concentrations can be achieved with both Cp40 and its PEGylated derivative, PEG-Cp40.
SInC: an accurate and fast error-model based simulator for SNPs, Indels and CNVs coupled with a read generator for short-read sequence data
Authors: Pattnaik Swetansu , Gupta Saurabh , Rao Arjun A , Panda Binay
Published: February 2014

Background

The rapid advancements in the field of genome sequencing are aiding our understanding on many biological systems. In the last five years, computational biologists and bioinformatics specialists have come up with newer, better and more efficient tools towards the discovery, analysis and interpretation of different genomic variants from high-throughput sequencing data. Availability of reliable simulated dataset is essential and is the first step towards testing any newly developed analytical tools for variant discovery. Although there are tools currently available that can simulate variants, none present the possibility of simulating all the three major types of variations (Single Nucleotide Polymorphisms, Insertions and Deletions and Copy Number Variations) and can generate reads taking a realistic error-model into consideration. Therefore, an efficient simulator and read generator is needed that can simulate variants taking the error rates of true biological samples into consideration.

Results

We report SInC (Snp, Indel and Cnv) an open-source variant simulator and read generator capable of simulating all the three common types of biological variants taking into account a distribution of base quality score from a most commonly used next-generation sequencing instrument from Illumina. SInC is capable of generating single- and paired-end reads with user-defined insert size and with high efficiency compared to the other existing tools. SInC, due to its multi-threaded capability during read generation, has a low time footprint. SInC is currently optimised to work in limited infrastructure setup and can efficiently exploit the commonly used quad-core desktop architecture to simulate short sequence reads with deep coverage for large genomes.

Conclusions

We have come up with a user-friendly multi-variant simulator and read-generator tools called SInC. SInC can be downloaded from http://sourceforge.net/projects/sincsimulator.
A shotgun antisense approach to the identification of novel essential genes in Pseudomonas aeruginosa
Authors: Rusmini Ruggero , Vecchietti Davide , Macchi Raffaella , Vidal-Aroca Faustino , Bertoni Giovanni
Published: February 2014

Background

Antibiotics in current use target a surprisingly small number of cellular functions: cell wall, DNA, RNA, and protein biosynthesis. Targeting of novel essential pathways is expected to play an important role in the discovery of new antibacterial agents against bacterial pathogens, such asPseudomonas aeruginosa, that are difficult to control because of their ability to develop resistance, often multiple, to all current classes of clinical antibiotics.

Results

We aimed to identify novel essential genes inP. aeruginosaby shotgun antisense screening. This technique was developed inStaphylococcus aureusand, following a period of limited success in Gram-negative bacteria, has recently been used effectively inEscherichia coli. To also target low expressed essential genes, we included some variant steps that were expected to overcome the non-stringent regulation of the promoter carried by the expression vector used for the shotgun antisense libraries. Our antisense screenings identified 33 growth-impairing single-locus genomic inserts that allowed us to generate a list of 28 “essential-for-growth” genes: five were “classical” essential genes involved in DNA replication, transcription, translation, and cell division; seven were already reported as essential in other bacteria; and 16 were “novel” essential genes with no homologs reported to have an essential role in other bacterial species. Interestingly, the essential genes in our panel were suggested to take part in a broader range of cellular functions than those currently targeted by extant antibiotics, namely protein secretion, biosynthesis of cofactors, prosthetic groups and carriers, energy metabolism, central intermediary metabolism, transport of small molecules, translation, post-translational modification, non-ribosomal peptide synthesis, lipopolysaccharide synthesis/modification, and transcription regulation. This study also identified 43 growth-impairing inserts carrying multiple loci targeting 105 genes, of which 25 have homologs reported as essential in other bacteria. Finally, four multigenic growth-impairing inserts belonged to operons that have never been reported to play an essential role.

Conclusions

For the first time inP. aeruginosa, we applied regulated antisense RNA expression and showed the feasibility of this technology for the identification of novel essential genes.
Restraint use in home care: a qualitative study from a nursing perspective
Authors: Scheepmans Kristien , Dierckx de Casterlé Bernadette , Paquay Louis , Van Gansbeke Hendrik , Boonen Steven , Milisen Koen
Published: February 2014

Background

Despite the growing demand for home care and preliminary evidence suggesting that the use of restraint is common practice in home care, research about restraint use in this setting is scarce.

Methods

To gain insight into the use of restraints in home care from the perspective of nurses, we conducted a qualitative explorative study. We conducted semi-structured face-to-face interviews of 14 nurses from Wit-Gele Kruis, a home-care organization in Flanders, Belgium. Interview transcripts were analyzed using the Qualitative Analysis Guide of Leuven.

Results

Our findings revealed a lack of clarity among nurses about the concept of restraint in home care. Nurses reported that cognitively impaired older persons, who sometimes lived alone, were restrained or locked up without continuous follow-up. The interviews indicated that the patient’s family played a dominant role in the decision to use restraints. Reasons for using restraints included “providing relief to the family” and “keeping the patient at home as long as possible to avoid admission to a nursing home.” The nurses stated that general practitioners had no clear role in deciding whether to use restraints.

Conclusions

These findings suggest that the issue of restraint use in home care is even more complex than in long-term residential care settings and acute hospital settings. They raise questions about the ethical and legal responsibilities of home-care providers, nurses, and general practitioners. There is an urgent need for further research to carefully document the use of restraints in home care and to better understand it so that appropriate guidance can be provided to healthcare workers.
Kaposi`s sarcoma associated herpesvirus infection among female sex workers and general population women in Shanghai, China: a cross-sectional study
Authors: Zhang Tiejun , Yang Ying , Yu Feng , Zhao Yanping , Lin Feifei , Minhas Veenu , Wood Charles , He Na
Published: February 2014

Background

Limited information on epidemiologic patterns of KSHV, with none focusing on heterosexual transmission, is available in mainland China. To clarify this, a cross-sectional study was conducted among a group of female sex workers (FSW) and general population women (GW) in Shanghai, China.

Methods

An anonymous questionnaire interview was administrated among 600 FSW and 600 GW. Blood samples were collected and tested for antibodies to KSHV, HSV-2, HIV, syphilis and HBsAg. Correlates of KSHV and HSV-2 were examined using multiple logistic regression analysis.

Results

None of the study participants were tested positive for HIV. The seroprevalence of KSHV, HSV-2 , HBV and syphilis was 10.0%, 52.2%, 12.3% and 10.5%, respectively for FSW, and was 11.0%, 15.3%, 9.8% and 2.8%, respectively for GW. KSHV seropositivity was not associated with syphilis and HSV-2 infection as well as sexual practices among either FSW or GW. Nevertheless, HSV-2 infection among FSW was independently associated with being ever married (OR = 1.59; 95%CI: 1.04-2.45), >5 years of prostitution (OR = 2.06; 95%CI: 1.16-3.68) and being syphilis positive (OR = 2.65; 95%CI: 1.43-4.93). HSV-2 infection among GW was independently associated with an age of >35 years (OR = 2.29; 95%CI: 1.07-4.93), having had more than 2 sex partners in the prior 12 months (OR = 6.44; 95%CI: 1.67-24.93) and being syphilis positive (OR = 3.94; 95%CI: 1.38-11.23). A gradual increase of prevalence with the prostitution time group was also detected for HSV-2 and syphilis, but not for KSHV.

Conclusions

KSHV is moderately and equivalently prevalent among FSW and GW. Heterosexual contact is not a predominant route for KSHV transmission among Chinese women.
Development and feasibility of a home-based education model for families of children with sickle cell disease
Authors: Hoyt Drazen Catherine , Abel Regina , Lindsey Terianne , King Allison A
Published: February 2014

Background

Children with sickle cell disease (SCD) commonly have cognitive deficits, even among toddlers. Much medical literature emphasizes disease-based factors to account for these deficits. However, the social environment plays a large role in child development. To address the specific needs of early childhood, a monthly hospital-based education program was initiated to educate parents about child development. Education sessions were poorly attended (20-25%) and deemed unsuccessful. This study describes the development and implementation of a home-based education service to teach parents about SCD, developmental milestones and positive parenting techniques.

Methods

This was a prospective, single-arm intervention to study the feasibility of a home-based caregiver education program for families with infants and toddlers with SCD. Parents of children aged 0-3 years with SCD from one Midwestern hospital were approached to participate in a home-based program. The program followed the Born to Learn™ curriculum provided through the Parents as Teachers™ National Center. Reminder calls or texts were provided the day before each visit. Results of the first twenty-six months of the program are presented.

Results

A total of 62% (56 of 91) of families approached agreed to participate; all were African American. The majority of caregivers were single mothers with a high school education or less and whose children had Medicaid for health coverage. The phenotypes of SCD represented in this sample were similar to those in the general SCD population. Over 26 months, 39 families received at least one home visit. Parents of infants (younger than 8 months) were more likely to participate in the home-based education program than parents of older children, (Fisher’s exact test, p < .001).

Conclusions

For participating families, home-based visits were a feasible method for reinforcing clinic education. About 43% of eligible families participated in the education, a two-fold increase in the poor attendance (20%) for a previous hospital-based program. A home visitation program for parents of infants with SCD could offer an effective approach to helping these children overcome adverse environmental conditions that are compounded by the complexities of a chronic health condition.
Structure to function prediction of hypothetical protein KPN_00953 (Ycbk) from Klebsiella pneumoniae MGH 78578 highlights possible role in cell wall metabolism
Authors: Teh Boon Aun , Choi Sy Bing , Musa Nasihah , Ling Few Ling , Cun See Too Wei , Salleh Abu Bakar , Najimudin Nazalan , Wahab Habibah A , Normi Yahaya M
Published: February 2014

Background

Klebsiella pneumoniae plays a major role in causing nosocomial infection in immunocompromised patients. Medical inflictions by the pathogen can range from respiratory and urinary tract infections, septicemia and primarily, pneumonia. As more K. pneumoniae strains are becoming highly resistant to various antibiotics, treatment of this bacterium has been rendered more difficult. This situation, as a consequence, poses a threat to public health. Hence, identification of possible novel drug targets against this opportunistic pathogen need to be undertaken. In the complete genome sequence of K. pneumoniae MGH 78578, approximately one-fourth of the genome encodes for hypothetical proteins (HPs). Due to their low homology and relatedness to other known proteins, HPs may serve as potential, new drug targets.

Results

Sequence analysis on the HPs of K. pneumoniae MGH 78578 revealed that a particular HP termed KPN_00953 (YcbK) contains a M15_3 peptidases superfamily conserved domain. Some members of this superfamily are metalloproteases which are involved in cell wall metabolism. BLASTP similarity search on KPN_00953 (YcbK) revealed that majority of the hits were hypothetical proteins although two of the hits suggested that it may be a lipoprotein or related to twin-arginine translocation (Tat) pathway important for transport of proteins to the cell membrane and periplasmic space. As lipoproteins and other components of the cell wall are important pathogenic factors, homology modeling of KPN_00953 was attempted to predict the structure and function of this protein. Three-dimensional model of the protein showed that its secondary structure topology and active site are similar with those found among metalloproteases where two His residues, namely His169 and His209 and an Asp residue, Asp176 in KPN_00953 were found to be Zn-chelating residues. Interestingly, induced expression of the cloned KPN_00953 gene in lipoprotein-deficient E. coli JE5505 resulted in smoother cells with flattened edges. Some cells showed deposits of film-like material under scanning electron microscope.

Conclusions

We postulate that KPN_00953 is a Zn metalloprotease and may play a role in bacterial cell wall metabolism. Structural biology studies to understand its structure, function and mechanism of action pose the possibility of utilizing this protein as a new drug target against K. pneumoniae in the future.
Sodium glucose cotransporter 1 ligand BLF501 as a novel tool for management of gastrointestinal mucositis
Authors: Cardani Diego , Sardi Claudia , La Ferla Barbara , D’Orazio Giuseppe , Sommariva Michele , Marcucci Fabrizio , Olivero Daniela , Tagliabue Elda , Koepsell Hermann , Nicotra Francesco , Balsari Andrea , Rumio Cristiano
Published: February 2014

Background

Recent studies demonstrated that engagement of sodium glucose transporter 1 (SGLT-1) by orally administered D-glucose protects the intestinal mucosa from lipopolysaccharide (LPS)-induced injury. We tested whether SGLT-1 engagement might protect the intestinal mucosa from doxorubicin (DXR)- and 5-fluorouracil (5-FU)-induced injury in animal models mimicking acute or chronic mucositis.

Methods

Mice were treated intraperitoneally with DXR, alone or in combination with 5-FU, and orally with BLF501, a glucose-derived synthetic compound with high affinity for SGLT-1. Intestinal mucosal epithelium integrity was assessed by histological analysis, cellular proliferation assays, real-time PCR gene expression assays and Western blot assays. Student’s t-test (paired two-tailed) and χ2 analyses were used for comparisons between groups. Differences were considered significant at p < 0.05.

Results

BLF501 administration in mice treated with DXR and/or 5-FU decreased the injuries to the mucosa in terms of epithelial integrity and cellular proliferative ability. Co-treatment with BLF501 led to a normal expression and distribution of both zonula occludens-1 (ZO-1) and beta-catenin, which were underexpressed after treatment with either chemotherapeutic agent alone. BLF501 administration also restored normal expression of caspase-3 and ezrin/radixin/moesin (ERM), which were overexpressed after treatment with DXR and 5-FU. In SGLT1-/- mice, BLF501 had no detectable effects. BLF501 administration in wild-type mice with growing A431 tumors did not modify antitumor activity of DXR.

Conclusions

BLF501-induced protection of the intestinal mucosa is a promising novel therapeutic approach to reducing the severity of chemotherapy-induced mucositis.
Pilot trial of Stop Delirium! (PiTStop) - a complex intervention to prevent delirium in care homes for older people: study protocol for a cluster randomised controlled trial
Authors: Heaven Anne , Cheater Francine , Clegg Andrew , Collinson Michelle , Farrin Amanda , Forster Anne , Godfrey Mary , Graham Liz , Grice Anne , Holt Rachel , Hulme Claire , Lloyd Ernie , Meads David , North Chris , Young John , Siddiqi Najma
Published: February 2014

Background

Delirium (or acute confusion) is a serious illness common in older people, in which a person’s thinking and perceptions may be affected. Reducing delirium is important because of the considerable distress it causes, and the poor outcomes associated with it, such as increased admissions to hospital, falls, mortality and costs to the National Health Service (NHS). Preventing delirium is possible using multicomponent interventions; successful interventions in hospitals have reduced it by one-third. However, there is little research to guide practice in care homes, where it is common because of the clustering of known risk factors (older age, frailty, and dementia). In previous work we developed a multicomponent intervention to prevent delirium in care homes, called Stop Delirium! The intervention was based upon evidence from the research literature relating to the prevention of delirium and on strategies to change professional practice. Before starting a large costly trial of Stop Delirium!, this pilot study will test and help improve the design and feasibility of the trial protocol.

Methods/Design

We plan to conduct a cluster randomised pilot trial in 14 care homes (independent residential and nursing). Following recruitment of residents (over 60 years, consenting or with consultee agreement, able to communicate in English, and not in palliative care) participating homes will be randomised, stratified by size of home and proportion of residents with dementia. Stop Delirium! will be delivered to intervention homes over 16 months, with controls receiving usual care. The primary outcome measure will be the presence of delirium on any day during a one-month post-intervention period.

We will collect data to determine 1) recruitment and attrition rates, 2) feasibility of various outcomes measurements, and 3) feasibility of capturing health resource use (resident diaries and by examining health records). We will estimate the between-cluster variation for the primary outcome, delirium occurrence.

Discussion

This pilot study will refine methods for the definitive trial. The lessons learnt will also contribute to implementing National Institute for Health and Clinical Excellence (NICE) delirium guidelines, which recommend multicomponent interventions for delirium prevention.

Trial registration

ISRCTN27972532.