bluuebunny/crossref_metadata_2025 huggingface dataset:
Six-minute walk distance in patients with chronic obstructive pulmonary disease
Authors: Andrianopoulos Vasileios , Holland Anne E , Singh Sally J , Franssen Frits ME , Pennings Herman-Jan , Michels Arent J , Smeenk Frank WJM , Vogiatzis Ioannis , Wouters Emiel FM , Spruit Martijn A
Published: March 2015

The use of different 6-min walk distance (6MWD) reference equations probably results in different predicted 6MWD reference values. We wished to investigate the impact of several 6MWD reference equations for adults in patients with chronic obstructive pulmonary disease (COPD) and factors accountable for different 6MWD% predicted values. Twenty-two 6MWD reference equations were applied to a data set of 2757 patients with COPD. The predicted 6MWD reference value of Troosters and colleagues was used as the point of reference. Four out of 21 remaining equations resulted in comparable 6MWD% predicted, 16 equations resulted in significantly higher 6MWD% predicted and 1 equation resulted in a significantly lower 6MWD% predicted. Similar differences in 6MWD% predicted were observed after stratification by sex. Body mass index and global initiative for chronic obstructive lung disease (GOLD) stage classification demonstrated varying results within and between the groups; 9 out of 21 equations resulted in comparable 6MWD% predicted in underweight patients but only 1 equation demonstrated comparable result in obese. Eight equations in GOLD I, whilst 5 out of 21 equations in GOLD IV resulted in comparable 6MWD% predicted. Existing 6MWD reference equations will give varying results. The choice of 6MWD reference equation should consider the consistency of 6-min walk test operating procedures and at least be specific for the country/region of origin.
Usability and Workload of Access Technology for People With Severe Motor Impairment
Authors: Pasqualotto Emanuele , Matuz Tamara , Federici Stefano , Ruf Carolin A. , Bartl Mathias , Olivetti Belardinelli Marta , Birbaumer Niels , Halder Sebastian
Published: March 2015

Background. Eye trackers are widely used among people with amyotrophic lateral sclerosis, and their benefits to quality of life have been previously shown. On the contrary, Brain-computer interfaces (BCIs) are still quite a novel technology, which also serves as an access technology for people with severe motor impairment. Objective. To compare a visual P300-based BCI and an eye tracker in terms of information transfer rate (ITR), usability, and cognitive workload in users with motor impairments. Methods. Each participant performed 3 spelling tasks, over 4 total sessions, using an Internet browser, which was controlled by a spelling interface that was suitable for use with either the BCI or the eye tracker. At the end of each session, participants evaluated usability and cognitive workload of the system. Results. ITR and System Usability Scale (SUS) score were higher for the eye tracker (Wilcoxon signed-rank test: ITR T = 9, P = .016; SUS T = 12.50, P = .035). Cognitive workload was higher for the BCI ( T = 4; P = .003). Conclusions. Although BCIs could be potentially useful for people with severe physical disabilities, we showed that the usability of BCIs based on the visual P300 remains inferior to eye tracking. We suggest that future research on visual BCIs should use eye tracking–based control as a comparison to evaluate performance or focus on nonvisual paradigms for persons who have lost gaze control.
Clinicopharmacological profile of the fixed-dose combination of aclidinium bromide and formoterol fumarate in the management of chronic obstructive pulmonary disease
Authors: Babu K. Suresh , Morjaria Jaymin B.
Published: March 2015

The recent Global Initiative for Chronic Obstructive Lung Disease (GOLD) chronic obstructive pulmonary disease (COPD) guidelines consider symptoms and exacerbation history in addition to the degree of airflow obstruction for classifying patients. The improvement of symptoms is principally provided by bronchodilators, using β2 agonists and antimuscarinic agents. Aclidinium bromide is a novel long-acting antimuscarinic agent licensed for use in patients with COPD. Novel fixed-dose combinations that are either licensed or in their late phase of development include vilanterol/umeclidinium, indacaterol/glycopyrronium, olodaterol/tiotropium and formoterol/aclidinium. Fixed-dose combinations of aclidinium/formoterol have been evaluated in COPD patients and evidence suggests that this is efficacious, safe, has a quick onset of action and is well tolerated. This review provides a clinico-pharmacological profile of this compound.
Rates of Deep Venous Thrombosis and Pulmonary Embolus After Anterior Cruciate Ligament Reconstruction
Authors: Erickson Brandon J. , Saltzman Bryan M. , Campbell Kirk A. , Fillingham Yale A. , Harris Joshua D. , Gupta Anil K. , Bach Bernard R.
Published: March 2015

Context:

Venous thromboembolic (VTE) disease is thought to be an uncommon but serious problem after anterior cruciate ligament (ACL) reconstruction. Rates of VTE after ACL reconstruction are not well documented.

Objective:

To determine the rates of deep vein thrombosis (DVT) and symptomatic pulmonary emboli (PE) after ACL reconstruction.

Data Sources:

Five publicly available databases (PubMed, Cochrane Database of Systematic Reviews, Scopus, Embase, and CINAHL Complete) were utilized.

Study Selection:

All studies that screened patients for DVT and reported rates of DVT and PE after ACL reconstruction were eligible for inclusion. Level 5 evidence, cadaver, biomechanical, and basic science studies; studies reporting only multiligament reconstruction outcomes; studies where rates of DVT and PE could not be separated out from patients undergoing other types of arthroscopic knee procedures; and classification studies were excluded.

Study Design:

Systematic review.

Level of Evidence:

Level 4.

Data Extraction:

All study, subject, and surgical data were analyzed. Descriptive statistics were calculated.

Results:

Six studies met the inclusion criteria, with a mean Modified Colman Methodology Score of 30 ± 8.22. A total of 692 patients (488 men [70.5%]; mean age, 31.6 ± 2.82 years; mean follow-up, 7 ± 18.4 months) underwent ACL reconstruction using either semitendinosus-gracilis autograft (77.6%), bone–patellar tendon–bone (BTB) autograft (22%), or allograft (0.4%). No patient received postoperative pharmacological anticoagulation. Fifty-eight patients (8.4%) had a DVT (81% below knee and 19% above knee), while only 1 patient (0.2%) had a symptomatic PE. When reported, 27% of DVT episodes were symptomatic.

Conclusion:

The rate of DVT after ACL reconstruction in patients who did not receive postoperative pharmacological anticoagulation is 8.4%, while the rate of symptomatic PE is 0.2%. Of the DVT episodes that occurred, 73% were asymptomatic.
Recognizing Diabetes in Children
Authors: Brown Catherine
Published: March 2015

Both type 1 diabetes and type 2 diabetes are on the rise in children. School nurses should be familiar with these conditions and have an understanding of who is more likely to be affected, what the presenting symptoms are, and how to support the student, family, and school personnel when a diagnosis is made. This article serves as a reference for school nurses and highlights key resources freely available for their use.
Σκύβαλα Happens: Edification from a Four-Letter Word in the Word of God?
Authors: Punch John David
Published: March 2015

St. Paul’s use of the term σκύβαλα in Philippians 3.8 seems to contradict his prohibition elsewhere of “unwholesome speech.” This article compares debated etymologies of the term, considers evidence of the term’s use in antiquity, and evaluates the warrant for its usage in contrast with other available terms. Lastly, it offers a conclusion about the appropriateness and inappropriateness of similar uses of coarse language by those who follow Paul in the Christian church.
How Many Idols Did Micah Have? (Judges 17.1–18.31)
Authors: Slager Don
Published: March 2015

This article examines the idols Micah had and how many there were. It looks at how various versions have handled the exegetical and textual problems concerning these idols.
Helping Bible Translators Recognize Linguistic Interference between Angolan Bantu Languages and Portuguese
Authors: Halme-Berneking Riikka
Published: March 2015

Bantu languages of Angola share many phonological, morpho-syntactical, and semantic features that differ from Portuguese. Angolan Bible translators use Portuguese Bible translations as their base texts. This paper explores some common examples of interference between the source and target languages in the translation of the Gospels and discusses how to help translators recognize interference in order to improve the fluency and naturalness of their translations. By training translators to recognize differences between their languages and the source language, a better-quality translation can be achieved at earlier stages in the process.
Deportation or Forgiveness in Hosea 1.6? Verb Valence Patterns and Translation Proposals
Authors: Dyk Janet , de Regt Lénart J. , Harmelink Bryan
Published: March 2015

In order to render a verb consistently within the syntactic pattern in which it occurs, it is necessary to take into account the presence of a direct object (one, multiple, or none), the possibility of an idiomatic expression involving the direct object, the lexical characteristics of the elements in the construction, and the presence and particular function of prepositions in relation to the verb. Lexicons often provide a broad range of meanings for a single verb, but because a pattern might be affected by the combination with other elements, it is not always clear under which conditions a specific significance is applicable. Exegetes and translators sometimes take the liberty of choosing rather freely from the offered dictionary glosses, apparently not being sufficiently aware that elements present in the context could pose restrictions on the choice of rendering. Using examples containing the Hebrew verbs עשׂה, נשׂא, and שׂים, the significance of the specific patterns in which these verbs occur is explored. Variety in the translations of these verbs is presented and analyzed. The insights inform a procedure for identifying the signification of Hebrew verbs in which a series of questions guides one to a consistent rendering of the pattern in which the verb occurs.
The paradoxes of solidarity: Cultural trauma and collective identity in Mao’s China
Authors: Gao Rui
Published: March 2015

The millions of Chinese people who had the misfortune of living through the War of Resistance Against Japan (hereinafter ‘the War’) experienced nearly unbearable trauma and pain. Such vivid and massively shared suffering and injustice, however, remained ultimately private and individual. For many years after the building of the People’s Republic of China, this suffering seldom found its way into the public sphere of expression. A chief goal of this paper is to delve into this curious phenomenon – namely, the ‘absence’ of a collective trauma of the War despite the human suffering – and seek to explain it from a cultural sociological point of view. To this end, the theory of cultural trauma is used and the relationship between various cultural structures in the process of trauma formation is explored. The absence of the trauma of the War should not be understood merely as a consequence of political necessity, but should be contextualized and comprehended within the web of meanings woven by powerful cultural structures that predominated in the public sphere at the time. The paper sets out two principal tasks:. first, the successful construction in Mao’s era of a class trauma that sought to form a new collectivity is traced; and, second, how the experience of the War fits or, rather, ‘unfits’ with this grand narrative of ‘class trauma’ is examined. Tracing representation of the War in the public sphere around the time, it is argued that the emergence of the War as a collective trauma was effectively ‘inhibited’ by the trauma of class struggle.
Towards a professional sociology on China
Authors: Wu Xiaogang
Published: March 2015

This article identifies two internal tensions that Chinese sociology has constantly encountered since the discipline was reestablished in 1979: public versus professional and indigenization versus internationalization. I argue that professionalization is a necessary and crucial step to achieving unity in the study of social changes in contemporary China and to contributing to general knowledge in the discipline of sociology.
Social Scientists’ Understanding of Academic Freedom in Addis Ababa University, Ethiopia
Authors: Degefa Demoze
Published: March 2015

The perennial debate about academic freedom engages with assessing the extent to which academic freedom has been exercised by academics by using some normative and quantitative approaches. Often studies on academic freedom deal with the extent to which institutions comply with norms in terms of the rights of the academics on some international standards. This article takes its departure by making an empirical investigation of how academics understand academic freedom by employing a qualitative approach. It presents an empirical investigation of the different conceptions of academic freedom among instructors of social sciences in Addis Ababa University. The study was undertaken from a phenomenographic point of view and four qualitatively different ways of understanding academic freedom, based on the distance between the self and the perceived threats to academic freedom, were identified. The relationship between the different ways of viewing academic freedom reminds one that more pragmatic provisions for academic freedom and policy debates need to begin which must be accommodative of academics’ views on the subject before making any meaningful point.
Managing Strategies for Higher Education Institutions in the UK
Authors: Ahmed Jashim Uddin , Ahmed Kamal Uddin , Shimul Md. Anwar Sadat , Zuñiga Roy
Published: March 2015

This article deals with strategic management issues in the higher education sector in the UK. The core idea is presented here with the argument that the principle and practice of strategic management are not only the concerns of senior management, but also an essential requirement at all levels of management of higher education. It shows that higher education institutions exist in a complex and changing environment with an increasing need for fast and effective strategic responses to external pressures. Having identified these issues, this article considers a form of strategic issues such as strategic management in higher education, three different levels of strategy and also discusses Porter’s five forces in the context of UK higher education sector. Though these issues are considered from a theoretical standpoint, they are linked to the competitive positioning and strategic management concepts being used in higher education.
The Effect of Family Characteristics on Higher Education Attendance in India
Authors: Pramanik Shaswati
Published: March 2015

Family characteristics in terms of parental education and income are an important influence on individual’s participation in higher education. In India it could be found that categorically those who are out of the higher education system belong to marginalized groups due to their economic class, caste, gender, religion etc. despite massive expansion of higher education. With this background, this article seeks to examine the effect of family income and parental education on an individual’s probability of attaining higher education in India. Besides these two variables, an individual’s likelihood of participation in higher education is influenced by social, religious and demographic characteristics for both rural and urban youth in India. Using multivariate logistic regression to analyze data from National Sample Survey (NSS) 68th Round (unit level records), the article examines how an individual’s participation in higher education is governed by his/her economic and social background and also by gender-related aspects. The results reveal that parental education and family income exert a direct effect on an individual’s propensity to participate in higher education. In terms of social and religious group, this youth belonging to Scheduled Tribe and Scheduled Caste have significantly lower odds of going to higher education compared to general category for the whole of India. Females are less likely to participate in higher education in rural area, while Hindu females in rural area are less probable to participate in higher education. Hence, this article seeks to contribute, from an economic perspective, to the growing number of empirical studies that have investigated the background factors that influence higher education participation.
Public Spending in Higher Education in India
Authors: Mitra Anuneeta
Published: March 2015

This article is an attempt to build an empirical ground for supporting the increased role of public funding in higher education. The rationale for the same becomes pertinent in the current scenario when ‘public good’ nature of higher education is rapidly eroding. Various measures like the proportion of GDP/GSDP spent and the trend of per capita public expenditure on higher education have been calculated from 1990–1991 to 2009–2010 using 2004–2005 constant price.1 The calculations are done at an all India level and also across the 15 major states.2 The study also measures the distribution of subsidy in higher education to assess if it is progressive/regressive among five quintile groups,3 across 15 major states, and at an all India level, using National Sample Survey 64th round (2007–2008) unit level records. The tool of benefit incidence analysis has been used to arrive at the results for the same. Suits index and concentration curves have been used to supplement the results. Although the results at an all India level show a pro-rich distribution of subsidy at the higher level of education, a state-wise analysis showcases varied results, on several occasions breaking the India level norm which warrants appropriate reflections on policy implications.
Review of Proton Pump Inhibitor Overuse in the US Veteran Population
Authors: Metaxas Evdokia S. , Bain Kevin T.
Published: March 2015

Objective: A growing body of evidence provides proof that proton pump inhibitors (PPIs) are overused in the general population and that such use is associated with adverse risks and unnecessary costs. Our objective was to systematically evaluate PPI overuse in the veteran population. Data Sources: A literature search using MEDLINE and CINHAL databases (1946-December 2014) was performed using the search term proton pump inhibitors coupled with each of the following key words: inappropriate use, misuse, and overuse. Searches were limited to studies and reviews in English language and human subjects. Additional references were identified from a review of literature citations. Study Selection and Data Extraction: All articles that centrally addressed the issue of PPI overuse were evaluated, following the PRISMA guidelines for systematic reviews. Data were extracted into Microsoft Excel 2013. Articles that focused on the pediatric or non-US veteran populations were excluded. Data Synthesis: Among 30 articles included, 5 evaluated PPI overuse in veterans. The reported prevalence rate of PPI overuse in veterans ranged from 33% to 67%. Several cases reported PPI-associated Clostridium difficile–associated diarrhea and pneumonia. One Veterans Affairs center reported the total cost of PPI overuse to be more than $200 000 based on over-the-counter costs and more than $1.5 million based on average wholesale price cost. Conclusions: PPI overuse is common among veterans and exposes them to adverse risks and costs the system enormous dollars. Based on the findings of this review, we provide recommendations to curb PPI overuse among veterans and in the Veterans Affairs system.
Comparison of Patients Receiving Long-Term Metformin Therapy and Vitamin B12 Monitoring
Authors: Farland Michelle Z. , McPheeters Chelsey M. , Renwick Rachel C. , Barlow Patrick B. , Williams Juli D. , Keeble Donald S. , Franks Andrea S.
Published: March 2015

Background: Metformin may cause vitamin B12 deficiency that can present with symptoms of peripheral neuropathy. Lack of vitamin B12 serum concentration monitoring could result in vitamin B12 deficiency progression, worsening of symptoms, and unnecessary medication. Objectives: The purpose of this study was to ( a) compare the influence of the rate of symptoms consistent with vitamin B12 deficiency on obtaining vitamin B12 serum concentrations in patients using metformin; ( b) assess if vitamin B12 serum concentrations were ordered as a routine monitoring parameter. Methods: This retrospective case–control study evaluated patients receiving metformin. Patients in the case group had documented symptoms or diagnosis of peripheral neuropathy or macrocytic anemia, while those in the control group did not. The primary outcome was frequency of vitamin B12 serum concentration assessment. The secondary outcomes included frequency of vitamin B12 serum concentration assessment for patients presenting with symptoms or diagnosis of peripheral neuropathy or macrocytic anemia. Results: Analysis included 355 patients (116 cases, 239 controls). The cases were 5 times more likely to have a serum vitamin B12 serum concentrations drawn versus controls (odds ratio [OR] = 5.83, 95% confidence interval [CI] = 3.47-9.77, P < .001). Patients with a diagnosis of peripheral neuropathy or macrocytic anemia were 4 times more likely to have a serum vitamin B12 concentration drawn than those who did not (peripheral neuropathy: OR = 4.92, 95% CI = 2.95-8.21, P < .001; macrocytic anemia: OR = 5.41, 95% CI = 1.30-20.97, P = .007). Conclusions: Cases were more likely to have vitamin B12 serum concentrations assessed than patients without symptoms. The majority of patients taking metformin did not have routine vitamin B12 serum concentration assessments for medication adverse event monitoring.
Effects of earplugs and eye masks combined with relaxing music on sleep, melatonin and cortisol levels in ICU patients: a randomized controlled trial
Authors: Hu Rong-Fang , Jiang Xiao-Ying , Hegadoren Kathleen M , Zhang You-Hua
Published: March 2015

Introduction

Intensive care unit (ICU) environmental factors such as noise and light have been cited as important causes of sleep deprivation in critically ill patients. Previous studies indicated that using earplugs and eye masks can improve REM sleep in healthy subjects in simulated ICU environment, and improve sleep quality in ICU patients. This study aimed to determine the effects of using earplugs and eye masks with relaxing background music on sleep, melatonin and cortisol levels in ICU patients.

Methods

Fifty patients who underwent a scheduled cardiac surgery and were expected to stay at least 2 nights in Cardiac Surgical ICU (CSICU) were included. They were randomized to sleep with or without earplugs and eye masks combined with 30-minute relaxing music during the postoperative nights in CSICU. Urine was analyzed for nocturnal melatonin and cortisol levels. Subjective sleep quality was evaluated using the Chinese version of Richards-Campbell Sleep Questionnaire (a visual analog scale, ranging 0–100).

Results

Data from 45 patients (20 in intervention group, 25 in control group) were analyzed. Significant differences were found between groups in depth of sleep, falling asleep, awakenings, falling asleep again after awakening and overall sleep quality (P < 0.05). Perceived sleep quality was better in the intervention group. No group differences were found in urinary melatonin levels and cortisol levels for the night before surgery, and the first and second nights post-surgery (P > 0.05). The urinary melatonin levels of the first and second postoperative nights were significantly lower than those of the night before surgery (P = 0.01). The opposite pattern was seen with urinary cortisol levels (P = 0.00).

Conclusion

This combination of non-pharmacological interventions is useful for promoting sleep in ICU adult patients; however, any influence on nocturnal melatonin levels and cortisol level may have been masked by several factors such as the timing of surgery, medication use and individual differences. Larger scale studies would be needed to examine the potential influences of these factors on biological markers and intervention efficacy on sleep.

Trial registration

Chinese Clinical Trial Registry: ChiCTR-IOR-14005511. Registered 21 November 2014.
Integrative epigenomic analysis of differential DNA methylation in urothelial carcinoma
Authors: Aine Mattias , Sjödahl Gottfrid , Eriksson Pontus , Veerla Srinivas , Lindgren David , Ringnér Markus , Höglund Mattias
Published: March 2015

Background

Urothelial carcinoma of the bladder (UC) is a common malignancy. Although extensive transcriptome analysis has provided insights into the gene expression patterns of this tumor type, the mechanistic underpinnings of differential methylation remain poorly understood. Multi-level genomic data may be used to profile the regulatory potential and landscape of differential methylation in cancer and gain understanding of the processes underlying epigenetic and phenotypic characteristics of tumors.

Methods

We perform genome-wide DNA methylation profiling of 98 gene-expression subtyped tumors to identify between-tumor differentially methylated regions (DMRs). We integrate multi-level publically available genomic data generated by the ENCODE consortium to characterize the regulatory potential of UC DMRs.

Results

We identify 5,453 between-tumor DMRs and derive four DNA methylation subgroups of UC with distinct associations to clinicopathological features and gene expression subtypes. We characterize three distinct patterns of differential methylation and use ENCODE data to show that tumor subgroup-defining DMRs display differential chromatin state, and regulatory factor binding preferences. Finally, we characterize an epigenetic switch involving the HOXA-genes with associations to tumor differentiation states and patient prognosis.

Conclusions

Genome-wide DMR methylation patterns are reflected in the gene expression subtypes of UC. UC DMRs display three distinct methylation patterns, each associated with intrinsic features of the genome and differential regulatory factor binding preferences. Epigenetic inactivation of HOX-genes correlates with tumor differentiation states and may present an actionable epigenetic alteration in UC.
Nanocrystalline cerium dioxide efficacy for gastrointestinal motility: potential for prokinetic treatment and prevention in elderly
Authors: Yefimenko Olena Yu , Savchenko Yuliya O , Falalyeyeva Tetyana M , Beregova Tetyana V , Zholobak Nadiya M , Spivak Mykola Ya , Shcherbakov Oleksandr B , Bubnov Rostyslav V
Published: March 2015

Background

Constipation is a common condition, with prevalence after 65 years, is a major colorectal cancer risk factor. Recent works have demonstrated advances in personalized, preventive nanomedicine, leading to the construction of new materials and nanodrugs, in particular, nanocrystalline cerium dioxide (NCD), having strong antioxidative prebiotic effect.

The aim of our studywas to investigate the influence of NCD on motor function of the stomach and colonin vivoand contractive activity of smooth muscles in different year-old rats.

Methods

We included 80 rats: 3- (weight 130–160 g,n = 40) and 24-month old (weight 390–450 g,n = 40), divided into four groups as follows: І—control group; rats of II–ІV groups were injected intragastrically one injection per day during 10 days, 3 ml of water 3 ml/kg stabilizing solution, аnd 1 mmol/ml NCD, respectively. In all animals, we recorded spontaneous and carbachol-stimulated (0.01 mg/kg) gastrointestinal tract motor activity. We used the index of motor activity (IMA), expressed in cmH2O, for characterization of the motor function. We investigated smooth muscle contraction by tenzometric method, studied the spontaneous and stimulated motility by ballonographic method.

Results

IMA reduced by 21.1 + 0.2% (p < 0.01) in the old rats of the control group compared with the young rats. A 10-day administration of NCD increased IMA in the stomach of young rats by 9.3% (р < 0.001) vs the control group. The exposure of NCD increased the amplitude of contraction to 34.2 ± 5.4 mN (n = 10) in the stomach of old rats and increased by 32.1 ± 2.4% vs the control group (p < 0.05). NCD did not influence acetylcholine (ACh) contractions in the stomach of young rats; however, in the stomach of old rats,Vnrincreased by 90 ± 15.2% (р < 0.001).

Conclusions

The index of motor activity is decreased in old rats. Nanocrystalline cerium dioxide increased the index of motor activity in all groups of rats and also evoked a significant increase of colon contractions in old rats.
Tumor necrosis factor-inducible gene 6 promotes liver regeneration in mice with acute liver injury
Authors: Wang Sihyung , Lee Ji-Seon , Hyun Jeongeun , Kim Jieun , Kim Seung U , Cha Hyuk-Jin , Jung Youngmi
Published: March 2015

Introduction

Tumor necrosis factor-inducible gene 6 protein (TSG-6), one of the cytokines released by human mesenchymal stem/stromal cells (hMSC), has an anti-inflammatory effect and alleviates several pathological conditions; however, the hepatoprotective potential of TSG-6 remains unclear. We investigated whether TSG-6 promoted liver regeneration in acute liver failure.

Methods

The immortalized hMSC (B10) constitutively over-expressing TSG-6 or empty plasmid (NC: Negative Control) were established, and either TSG-6 or NC-conditioned medium (CM) was intraperitoneally injected into mice with acute liver damage caused by CCl4. Mice were sacrificed at 3 days post-CM treatment.

Results

Higher expression and the immunosuppressive activity of TSG-6 were observed in CM from TSG-6-hMSC. The obvious histomorphological liver injury and increased level of liver enzymes were shown in CCl4-treated mice with or without NC-CM, whereas those observations were markedly ameliorated in TSG-6-CM-treated mice with CCl4. Ki67-positive hepatocytic cells were accumulated in the liver of the CCl4 + TSG-6 group. RNA analysis showed the decrease in both of inflammation markers, tnfα, il-1β, cxcl1 and cxcl2, and fibrotic markers, tgf-β1, α-sma and collagen α1, in the CCl4 + TSG-6 group, compared to the CCl4 or the CCl4 + NC group. Protein analysis confirmed the lower expression of TGF-β1 and α-SMA in the CCl4 + TSG-6 than the CCl4 or the CCl4 + NC group. Immunostaining for α-SMA also revealed the accumulation of the activated hepatic stellate cells in the livers of mice in the CCl4 and CCl4 + NC groups, but not in the livers of mice from the CCl4 + TSG-6 group. The cultured LX2 cells, human hepatic stellate cell line, in TSG-6-CM showed the reduced expression of fibrotic markers, tgf-β1, vimentin and collagen α1, whereas the addition of the TSG-6 antibody neutralized the inhibitory effect of TSG-6 on the activation of LX2 cells. In addition, cytoplasmic lipid drops, the marker of inactivated hepatic stellate cell, were detected in TSG-6-CM-cultured LX2 cells, only. The suppressed TSG-6 activity by TSG-6 antibody attenuated the restoration process in livers of TSG-6-CM-treated mice with CCl4.

Conclusions

These results demonstrated that TSG-6 contributed to the liver regeneration by suppressing the activation of hepatic stellate cells in CCl4-treated mice, suggesting the therapeutic potential of TSG-6 for acute liver failure.
Induction, expression and characterisation of laccase genes from the marine-derived fungal strains Nigrospora sp. CBMAI 1328 and Arthopyrenia sp. CBMAI 1330
Authors: Passarini Michel Rodrigo Zambrano , Ottoni Cristiane Angelica , Santos Cledir , Lima Nelson , Sette Lara Durães
Published: March 2015

The capability of the fungi Nigrospora sp. CBMAI 1328 and Arthopyrenia sp. CBMAI 1330 isolated from marine sponge to synthesise laccases (Lcc) in the presence of the inducer copper (1–10 μM) was assessed. In a liquid culture medium supplemented with 5 μM of copper sulphate after 5 days of incubation, Nigrospora sp. presented the highest Lcc activity (25.2 U·L−1). The effect of copper on Lcc gene expression was evaluated by reverse transcriptase polymerase chain reaction. Nigrospora sp. showed the highest gene expression of Lcc under the same conditions of Lcc synthesis. The highest Lcc expression by the Arthopyrenia sp. was detected at 96 h of incubation in absence of copper. Molecular approaches allowed the detection of Lcc isozymes and suggest the presence of at least two undescribed putative genes. Additionally, Lcc sequences from the both fungal strains clustered with other Lcc sequences from other fungi that inhabit marine environments.
Precise spatial restriction of BMP signaling is essential for articular cartilage differentiation
Authors: Ray Ayan , Singh Pratik Narendra Pratap , Sohaskey Michael L. , Harland Richard M. , Bandyopadhyay Amitabha
Published: March 2015

The articular cartilage, which lines the joints of the limb skeleton, is distinct from the adjoining transient cartilage, and yet, it differentiates as a unique population within a contiguous cartilage element. Current literature suggests that articular cartilage and transient cartilage originate from different cell populations. Using a combination of lineage tracing and pulse-chase of actively proliferating chondrocytes, we here demonstrate that, similar to transient cartilage, embryonic articular cartilage cells also originate from the proliferating chondrocytes situated near the distal ends of skeletal anlagen. We show that nascent cartilage cells are capable of differentiating as articular or transient cartilage, depending on exposure to Wnt or BMP signaling, respectively. The spatial organization of the articular cartilage results from a band of Nog-expressing cells, which insulates these proliferating chondrocytes from BMP signaling and allows them to differentiate as articular cartilage under the influence of Wnt signaling emanating from the interzone. Through experiments conducted in both chick and mouse embryos we have developed a model explaining simultaneous growth and differentiation of transient and articular cartilage in juxtaposed domains.
Histone deacetylase 1 and 2 regulate Wnt and p53 pathways in the ureteric bud epithelium
Authors: Chen Shaowei , Yao Xiao , Li Yuwen , Saifudeen Zubaida , Bachvarov Dimcho , El-Dahr Samir S.
Published: March 2015

Histone deacetylases (HDACs) regulate a broad range of biological processes through removal of acetyl groups from histones as well as non-histone proteins. Our previous studies showed that Hdac1 and Hdac2 are bound to promoters of key renal developmental regulators and that HDAC activity is required for embryonic kidney gene expression. However, the existence of many HDAC isoforms in embryonic kidneys raises questions concerning the possible specificity or redundancy of their functions. We report here that targeted deletion of both the Hdac1 and Hdac2 genes from the ureteric bud (UB) cell lineage of mice causes bilateral renal hypodysplasia. One copy of either Hdac1 or Hdac2 is sufficient to sustain normal renal development. In addition to defective cell proliferation and survival, genome-wide transcriptional profiling revealed that the canonical Wnt signaling pathway is specifically impaired in UBHdac1,2−/− kidneys. Our results also demonstrate that loss of Hdac1 and Hdac2 in the UB epithelium leads to marked hyperacetylation of the tumor suppressor protein p53 on lysine 370, 379 and 383; these post-translational modifications are known to boost p53 stability and transcriptional activity. Genetic deletion of p53 partially rescues the development of UBHdac1,2−/− kidneys. Together, these data indicate that Hdac1 and Hdac2 are crucial for kidney development. They perform redundant, yet essential, cell lineage-autonomous functions via p53-dependent and -independent pathways.
Vitamin K reduces hypermineralisation in zebrafish models of PXE and GACI
Authors: Mackay Eirinn W. , Apschner Alexander , Schulte-Merker Stefan
Published: March 2015

The mineralisation disorder pseudoxanthoma elasticum (PXE) is associated with mutations in the transporter protein ABCC6. Patients with PXE suffer from calcified lesions in the skin, eyes and vasculature, and PXE is related to a more severe vascular calcification syndrome called generalised arterial calcification of infancy (GACI). Mutations in ABCC6 are linked to reduced levels of circulating vitamin K. Here, we describe a mutation in the zebrafish (Danio rerio) orthologue abcc6a, which results in extensive hypermineralisation of the axial skeleton. Administration of vitamin K to embryos was sufficient to restore normal levels of mineralisation. Vitamin K also reduced ectopic mineralisation in a zebrafish model of GACI, and warfarin exacerbated the mineralisation phenotype in both mutant lines. These data suggest that vitamin K could be a beneficial treatment for human patients with PXE or GACI. Additionally, we found that abcc6a is strongly expressed at the site of mineralisation rather than the liver, as it is in mammals, which has significant implications for our understanding of the function of ABCC6.
Maintenance of Drosophila germline stem cell sexual identity in oogenesis and tumorigenesis
Authors: Shapiro-Kulnane Laura , Smolko Anne Elizabeth , Salz Helen Karen
Published: March 2015

Adult stem cells maintain tissue homeostasis by balancing self-renewal and differentiation. In Drosophila females, germline stem cells (GSCs) require Sex lethal (Sxl) to exit the stem cell state and to enter the differentiation pathway. Without Sxl GSCs do not differentiate and instead form tumors. Previous studies have shown that these tumors are not caused by a failure in the self-renewal/differentiation switch. Here, we show that Sxl is also necessary for the cell-autonomous maintenance of germ cell female identity and demonstrate that tumors are caused by the acquisition of male characteristics. Germ cells without Sxl protein exhibit a global derepression of testis genes, including Phf7, a male germline sexual identity gene. Phf7 is a key effector of the tumor-forming pathway, as it is both necessary and sufficient for tumor formation. In the absence of Sxl protein, inappropriate Phf7 expression drives tumor formation through a cell-autonomous mechanism that includes sex-inappropriate activation of Jak/Stat signaling. Remarkably, tumor formation requires a novel response to external signals emanating from the GSC niche, highlighting the importance of interactions between mutant cells and the surrounding normal cells that make up the tumor microenvironment. Derepression of testis genes, and inappropriate Phf7 expression, is also observed in germ cell tumors arising from the loss of bag of marbles (bam), demonstrating that maintenance of female sexual identity requires the concerted actions of Sxl and bam. Our work reveals that GSCs must maintain their sexual identity as they are reprogrammed into a differentiated cell, or risk tumorigenesis.
Neurodegeneration severity can be predicted from early microglia alterations monitoredin vivoin a mouse model of chronic glaucoma
Authors: Bosco Alejandra , Romero Cesar O. , Breen Kevin T. , Chagovetz Alexis A. , Steele Michael R. , Ambati Balamurali K. , Vetter Monica L.
Published: March 2015

Microglia serve key homeostatic roles, and respond to neuronal perturbation and decline with a high spatiotemporal resolution. The course of all chronic CNS pathologies is thus paralleled by local microgliosis and microglia activation, which begin at early stages of the disease. However, the possibility of using live monitoring of microglia during early disease progression to predict the severity of neurodegeneration has not been explored. Because the retina allows live tracking of fluorescent microglia in their intact niche, here we investigated their early changes in relation to later optic nerve neurodegeneration. To achieve this, we used the DBA/2J mouse model of inherited glaucoma, which develops progressive retinal ganglion cell degeneration of variable severity during aging, and represents a useful model to study pathogenic mechanisms of retinal ganglion cell decline that are similar to those in human glaucoma. We imaged CX3CR1+/GFP microglial cells in vivo at ages ranging from 1 to 5 months by confocal scanning laser ophthalmoscopy (cSLO) and quantified cell density and morphological activation. We detected early microgliosis at the optic nerve head (ONH), where axonopathy first manifests, and could track attenuation of this microgliosis induced by minocycline. We also observed heterogeneous and dynamic patterns of early microglia activation in the retina. When the same animals were aged and analyzed for the severity of optic nerve pathology at 10 months of age, we found a strong correlation with the levels of ONH microgliosis at 3 to 4 months. Our findings indicate that live imaging and monitoring the time course and levels of early retinal microgliosis and microglia activation in glaucoma could serve as indicators of future neurodegeneration severity.
Mass-Resolved Velocity Map Imaging of Doubly Charged Photofragments from C60
Authors: Katayanagi Hideki , Mitsuke Koichiro
Published: March 2015

Mass-resolved velocity map images have been measured for C60−2n2+ and C60−2n3+ (n ≥ 1) produced by photoionization of C60 with synchrotron radiation. A four-element electrostatic compound lens system was substituted for a conventional three-element system. This produced excellent time resolution, i.e., good mass-to-charge resolution, and negligible overlap between neighboring cluster ions. The translational temperatures for the C60−2n2+ ions were estimated from their velocity map images by assuming the Maxwell–Boltzmann distributions. Moreover, the improved resolution allowed observing a two-dimensional (2D) projection of three-dimensional velocity distribution of each fragment. The 2D projection of C582+ results from convolution of a narrow velocity distribution of the C60 molecular beam and a nascent isotropic profile of photodissociated C582+.
Efficiency-improving technologies for tourism activities in municipalities
Authors: Лагусев Юрий , Lagusev Yuriy
Published: March 2015

In connection with the launch of the "Strategy of development of tourism in the Russian Federation until 2020", approved by the Decree of the Government of the Russian Federation on May 31, 2014 №941-p, opportunities for coordination of tourism activities of municipalities have increased significantly. The complex of effective mechanisms is presented in the Strategy and Action Plan for its implementation, and they have opened up great opportunities for municipalities to develop the potential for domestic tourism. The primary purposes of the current step for the coordination of tourism activities in municipalities are to assist in the promotion of tourist resources of small cities, towns, and villages, programming event-tourism activities taking place in towns of Russia, participation in festivals of Russian towns, development of measures to support efforts to promote tourism services in small cities of Russia, including through public-private partnerships. This corresponds to the documents of Federal Target Program "Development of domestic and inbound tourism in the Russian Federation (2011—2018 years) " in terms of solving the problem of the development of tourist and recreational complex of the Russian Federation. The article is based on materials of the research carried out with the direct participation of the author, the main result of which is the development of the program content of the subject "Management of tourism in at state and municipal levels " in the programme of master training 43.04.02 "Tourism ". The article deals with the organizational support of the process of coordination of tourism activities at the state and municipal levels, aimed at obtaining a specific socio-economic result of the introduction of innovative technologies. The results obtained directly by the author are based on a fairly extensive empirical basis, which consists of the legal documents developed in the regions and municipalities for tourist activities coordination, as well as the programs and subprograms of tourism development in regions and municipalities. Technology developed to improve the efficiency of tourism activities in municipalities take into account the requirements of government agencies, businesses and social forces aimed at the development of tourism in the Russian Federation, and they are conducive to the processes of self-identification and promotion of domestic tourism. Tourism in Russia today is more than an economic phenomenon; it is, above all, an opportunity to carry out educational activities by means of tourism, to educate the historical memory of the population.
On the concept of cultural policy as a social system
Authors: Новичков Николай , Novichkov Nikolay
Published: March 2015

The article discusses the features of the concept of cultural policy as a social system. In particular the authors notes that the culture as a system has six major manifestations: as an element of the quality of life of modern man; as part of creative economy; as a system of spiritual values, attitudes, orientations and motives of a human and other elements of society; as a creative process and the whole set of artistic activities; as cultural heritage; as an entire population of people who identify themselves with a particular social system based on common cultural traits ("cultural codes"). The article also provides an analysis of some of the definitions of cultural policy. Marked are milestones in the history of cultural policy and formulated are the basic features of the past seven cultural revolutions as qualitative changes in the role of culture in society. In particular noted that, currently, the culture is going through a period of "self-realization " and is on the verge of becoming a total social phenomenon. The article notes the connection of cultural policy with "high politics", as well as with innovation policy. The aspects of ideology as a cultural phenomenon are also considered. In addition, the paper focuses on the role of cultural policies in the modern economic development. In particular noted that the implementation of cultural policy stimulates the emergence of more creative people, which clearly leads to their interaction with entrepreneurs who, in turn, too, as a rule, are creative people, and entrepreneurship has all the necessary features of creative activity. In general, we can make a clear conclusion that cultural policy as a social system is manifested in all spheres of human activities, and culture as a system is gradually acquiring a comprehensive character.
How to secure funds from the National Lottery
Authors: Best Brin
Published: March 2015

Brin Best provides advice on how schools can tap into the vast resources of the National Lottery, which has injected over £32 billion into good causes since 1994.
Relieving musculoskeletal pain
Authors: Bostock-Cox Beverley
Published: March 2015

Effective pain therapy can make a considerable difference to quality of life, says Beverley Bostock-Cox
Understanding FGM and its impact
Authors: Dominguez-Garcia Lazara
Published: March 2015

An awareness of female genital mutilation will prepare nurses, writes Lazara Dominguez-Garcia
Dried blood spot testing in infants at risk of hepatitis B
Authors: Olley Matthew , Keel Philip , Mandal Sema
Published: March 2015

Babies born to hepatitis B-positive mothers are at high risk of infection. Practice nurses can play a vital role in immunizing and performing follow-up testing in these infants