bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of structured planned post discharge support to patients with chronic obstructive pulmonary disease for reducing readmission rates: a systematic review
Authors: Pedersen Preben Ulrich , Ersgard Karen Bagger , Soerensen Tina Brandt , Larsen Palle
Published: August 2017

EXECUTIVE SUMMARY

Background

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease, characterized by airflow limitation. The disease has a significant impact on the lives of patients and is a challenge for the health care due to readmissions to hospitals.

Objectives

This review aimed to identify, appraise and synthesize the best available evidence on the effectiveness of discharge interventions that can reduce readmission of patients with COPD.

Types of participants

Hospitalized patients, aged 18 years or over, who had been diagnosed with COPD and were admitted to hospital due to acute exacerbation.

Types of interventions

Studies that evaluated discharge interventions that supported patients managing symptoms of COPD.

Types of studies

Randomized controlled trials, non-randomized controlled trials, quasi-experimental or cohort studies.

Outcomes

Readmission, defined as hospitalization to the same or different hospital for any reason within the following year after discharge.

Search strategy

Multiple databases (PubMed, Embase, CINAHL, the Cochrane Library, Pedro, Web of Science, Turning Research Into Practice [Trip] and Scopus) were searched from 1990 to June 2015. Studies published in English or Scandinavian.

Methodological quality

Two independent reviewers used the standard critical appraisal tool from the Joanna Briggs Institute to assess the methodological quality of studies. All studies were of good methodological quality.

Data extraction

The process of data extraction was undertaken independently by two reviewers using tools from the Joanna Briggs Institute.

Data synthesis

A narrative description of each study was performed. Outcomes were reported as the event rate (ER) in the intervention and control groups. Based on the ER relative risk reduction (RRR), absolute risk reduction (ARR), the number needed to treat (NNT), and relative risk (RR) with 95% confidence intervals were calculated. Continuous data were reported in natural units.

Results

This review includes ten studies all testing a mix of interventions. A meta-analysis included six studies, four at 30 days follow-up with RR 0.67 (0.45 to 0.98) and 180 days follow-up with RR 0.74 (0.51 to 1.08). The analysis could not identify a single set of interventions that could be recommended.

Conclusions

Post discharge support and interventions in patients with COPD significantly reduce the readmission rate within 30 days after discharge from hospital and the interventions may significantly reduce readmission up to 180 days after initial discharge. This is a significant finding from the clinical and practical perspective.
Pediatric post-anesthesia care unit discharge criteria: a scoping review protocol
Authors: Ryals Mary , Palokas Michelle
Published: August 2017

Review objective/question:

The objectives of this review are to explore existing literature on discharge criteria, tools and strategies utilized in pediatric post-anesthesia care units (PACUs) after outpatient surgery, examine and conceptually map the evidence, and identify gaps in the literature.

Specifically, the review question is: what criteria, tools and strategies are being used in pediatric PACUs for discharge?
Interaction of ammonia and hydrogen with tungsten at elevated temperature studied by gas flow through a capillary
Authors: Markelj Sabina , Založnik Anže , Čadež Iztok
Published: August 2017

The interaction of ammonia and hydrogen (H2 and D2) was studied by flowing pure gas or gas mixture through a hot tungsten capillary. The composition of the gas after passing the capillary was analyzed by mass spectrometry as a function of capillary temperature. Specific temperatures were identified where changes in mass spectra take place indicating thermal decomposition and isotope exchange channels. Measurements with pure ammonia and deuterium provided new data for the thermal decomposition of these molecules on hot tungsten. Ammonia gets effectively decomposed at around 900 K in the tungsten capillary, and only 7% of ammonia survives through the capillary at temperatures above 1100 K. By studying the production and desorption of HD in ammonia and deuterium mixture, the authors show that D2 molecules can get adsorbed on tungsten dissociatively only at temperatures above 1300 K in the presence of nitrogen or ammonia fragments. An adsorption barrier of 0.17 eV is determined for this case. A comparison of adsorption barrier of tungsten with that of native oxide on the surface is given when the mixture of H2 and D2 was flown through the hot tungsten capillary. Above 1300 K capillary temperature, H/D isotope exchange took place in the ammonia molecule on the surface yielding 1% of exchange as derived from the increase in ion current of ND3 in comparison to NH3.
Rippling pattern of distortion product otoacoustic emissions evoked by high-frequency primaries in guinea pigs
Authors: Burwood George W. S. , Russell Ian J. , Lukashkin Andrei N.
Published: August 2017

The origin of ripples in distortion product otoacoustic emission (DPOAE) amplitude which appear at specific DPOAE frequencies during f1 tone sweeps using fixed high frequency f2 (>20 kHz) in guinea pigs is investigated. The peaks of the ripples, or local DPOAE amplitude maxima, are separated by approximately half octave intervals and are accompanied by phase oscillations. The local maxima appear at the same frequencies in DPOAEs of different order and velocity responses of the stapes and do not shift with increasing levels of the primaries. A suppressor tone had little effect on the frequencies of the maxima, but partially suppressed DPOAE amplitude when it was placed close to the f2 frequencies. These findings agree with earlier observations that the maxima occur at the same DPOAE frequencies, which are independent of the f2 and the primary ratio, and thus are likely to be associated with DPOAE propagation mechanisms. Furthermore, the separation of the local maxima by approximately half an octave may suggest that the maxima are due to interference of the travelling waves along the basilar membrane at the frequency of the DPOAE. It is suggested that the rippling pattern appears because of interaction between DPOAE reverse travelling waves with standing waves formed in the cochlea.
Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9
Authors: Niu Dong , Wei Hong-Jiang , Lin Lin , George Haydy , Wang Tao , Lee I-Hsiu , Zhao Hong-Ye , Wang Yong , Kan Yinan , Shrock Ellen , Lesha Emal , Wang Gang , Luo Yonglun , Qing Yubo , Jiao Deling , Zhao Heng , Zhou Xiaoyang , Wang Shouqi , Wei Hong , Güell Marc , Church George M. , Yang Luhan
Published: August 2017

Taking the PERVs out of pigs

With the severe shortage of organs needed for transplants, xenotransplantation (transplantation of nonhuman organs to humans) offers an alternative source. Some pig organs have similar size and function to those of humans. The challenge is that the pig genome harbors porcine endogenous retroviruses (PERVs) that can potentially pass to humans with possibly damaging consequences. Niu
et al.
generated pigs in which all copies of PERVs were inactivated by CRISPR-Cas9 genome engineering (see the Perspective by Denner). Not only does this work provide insights into PERV activity, but it also opens the door to a safer source of organs and tissues for pig-to-human xenotransplantation.

Science
, this issue p.
1303
; see also p.
1238
Draft Genome Sequence of the Endophytic Bacillus aryabhattai Strain SQU-R12, Identified from
Phoenix dactylifera
L. Roots
Authors: Yaish Mahmoud W.
Published: August 2017

Bacillus aryabhattai
strain SQU-R12 was isolated from date palm seedlings, where it showed a growth-promoting capacity by being able to synthesize indole-3-acetic acid phytohormone and reduce ethylene biosynthesis by producing 1-aminocyclopropane-1-carboxylic acid deaminase. The draft genome sequence of this strain is reported here.
Autoimmune gastrointestinal dysmotility due to small cell lung cancer
Authors: Lipowska Anna Maria , Micic Dejan , Cavallo Allison , McDonald Edwin
Published: August 2017

The diagnosis of autoimmune gastrointestinal dysmotility requires a high level of clinical suspicion when standard work-up is unrevealing. We report the case of a 56-year-old male patient with history of tobacco use and a subacute presentation of weight loss, vomiting and cerebellar ataxia. The discovery of paraneoplastic type 1 antineuronal nuclear antibodies and neuronal acetylcholine receptor antibodies led to further directed imaging and diagnostic studies in spite of prior negative chest imaging. Bronchoscopy with endobronchial ultrasound was used to confirm a diagnosis of small cell lung cancer and paraneoplastic syndrome as the cause of the presenting upper gastrointestinal symptoms.
Cost-effectiveness of club-foot treatment in low-income and middle-income countries by the Ponseti method
Authors: Grimes Caris E , Holmer Hampus , Maraka Jane , Ayana Birhanu , Hansen Linda , Lavy Christopher B D
Published: August 2017

Background

Club foot is a common congenital deformity affecting 150 000–200 000 children every year. Untreated patients end up walking on the side or back of the affected foot, with severe social and economic consequences. Club foot is highly treatable by the Ponseti method, a non-invasive technique that has been described as highly suitable for use in resource-limited settings. To date, there has been no evaluation of its cost-effectiveness ratio, defined as the cost of averting one disability-adjusted life year (DALY), a composite measure of the impact of premature death and disability. In this study, we aimed to calculate the average cost-effectiveness ratio of the Ponseti method for correcting club foot in sub-Saharan Africa.

Methods

Using data from 12 sub-Saharan African countries provided by the international non-profit organisation CURE Clubfoot, which implements several Ponseti treatment programmes around the world, we estimated the average cost of the point-of-care treatment for club foot in these countries. We divided the cost of treatment with the average number of DALYs that can be averted by the Ponseti treatment, assuming treatment is successful in 90% of patients.

Results

We found the average cost of the Ponseti treatment to be US$167 per patient. The average number of DALYs averted was 7.42, yielding a cost-effectiveness ratio of US$22.46 per DALY averted. To test the robustness of our calculation different variables were used and these yielded a cost range of US$5.28–29.75. This is less than a tenth of the cost of many other treatment modalities used in resource-poor settings today.

Conclusions

The Ponseti method for the treatment of club foot is cost-effective and practical in a low-income country setting. These findings could be used to raise the priority for implementing Ponseti treatment in areas where patients are still lacking access to the life-changing intervention.
Obesity is a strong predictor of worse clinical outcomes and treatment responses in early rheumatoid arthritis: results from the SWEFOT trial
Authors: Levitsky Adrian , Brismar Kerstin , Hafström Ingiäld , Hambardzumyan Karen , Lourdudoss Cecilia , van Vollenhoven Ronald F , Saevarsdottir Saedis
Published: August 2017

Objectives

The aim of this paper was to analyse the impact of obesity, in addition to known predictors, on disease outcome in early rheumatoid arthritis (RA).

Methods

Body mass index (BMI) was available in 260 patients from the Swedish pharmacotherapy trial (SWEFOT). Differences in disease activity (DAS28), functional impairment (HAQ), pain (Visual Analogue Scale, VAS-pain) and radiographic damage were evaluated over 24 months between BMI categories (obese BMI >30, n=43; overweight BMI=25–29.9, n=74; normal BMI <25, n=143) using non-parametric testing. Predictors of European League Against Rheumatism non-remission (DAS28 ≥2.6) at 24 months of follow-up were evaluated using binary univariate and multivariate logistic regression.

Results

Obesity at baseline was associated with worse continuous-scale clinical outcomes over 24 months (DAS28, HAQ and VAS-pain at last visit: obese vs normal: p<0.001; obese vs overweight: p<0.05). Furthermore, obese patients compared with non-obese patients had significantly greater odds of non-remission at 24 months (adjusted OR (aOR) 5.2; 95% CI 1.8 to 15.2). Other independent predictors were female sex (aOR 2.6; 95% CI 1.1 to 5.8), current smoking (aOR 2.6; 95% CI 1.1 to 6.3) and HAQ (per-unit increase, aOR 1.9; 95% CI 1.1 to 3.4). The pattern was similar among seropositive and seronegative patients; and in the subgroups of methotrexate responders and patients randomised at 3 months to add-on of sulfasalazine+hydroxychloroquine, although not significant with add-on of infliximab. Obesity had no independent association to radiographic progression.

Conclusions

In this early RA trial reflecting today’s standard treatment, obesity, in addition to sex, smoking and functional impairment strongly lowered the chance of attaining good clinical outcomes, including remission, today’s treatment goal. This highlights the importance of considering lifestyle modification as one of the cornerstones of RA care.

Trial registration number

NCT00764725; Post-results. WHO database at the Karolinska University Hospital: CT20080004.
Cross-sectional study to evaluate Trichomonas vaginalis positivity in women tested for Neisseria gonorrhoeae and Chlamydia trachomatis, attending genitourinary medicine and primary care clinics in Bristol, South West England
Authors: Nicholls Jane E , Turner Katy M E , North Paul , Ferguson Ralph , May Margaret T , Gough Karen , Macleod John , Muir Peter , Horner Patrick J
Published: August 2017

Background

Highly sensitive, commercial nucleic acid amplification tests (NAAT) for Trichomonas vaginalis have only recently been recommended for use in the UK. While testing for T. vaginalis is routine in symptomatic women attending genitourinary medicine (GUM) clinics, it is rare in asymptomatic women or those attending primary care. The aim of this study was to evaluate the positivity of T. vaginalis using a commercial NAAT, in symptomatic and asymptomatic women undergoing testing for chlamydia and gonorrhoea in GUM and primary care settings.

Methods

Samples from 9186 women undergoing chlamydia and gonorrhoea testing in South West England between May 2013 and Jan 2015 were also tested for T. vaginalis by NAAT alongside existing tests.

Results

T. vaginalis positivity using NAAT was as follows: in GUM 4.5% (24/530, symptomatic) and 1.7% (27/1584, asymptomatic); in primary care 2.7% (94/3499, symptomatic) and 1.2% (41/3573, asymptomatic). Multivariable regression found that in GUM older age, black ethnicity and deprivation were independent risk factors for T. vaginalis infection. Older age and deprivation were also risk factors in primary care. Testing women presenting with symptoms in GUM and primary care using TV NAATs is estimated to cost £260 per positive case diagnosed compared with £716 using current microbiological tests.

Conclusions

Aptima TV outperforms existing testing methods used to identify T. vaginalis infection in this population. An NAAT should be used when testing for T. vaginalis in women who present for testing with symptoms in primary care and GUM, based on test performance and cost.
Compliance with smoke-free legislation and smoking behaviour: observational field study from Punjab, India
Authors: Goel Sonu , Sharma Deepak , Gupta Rakesh , Mahajan Vini
Published: August 2017

Background

Indian smoke-free legislation requires prohibition of smoking at public places and owners of public places to display ‘no smoking’ signages.

Aims and objectives

The study aims to assess the compliance of public places with smoke-free legislation and determine the factors associated with active smoking in public places.

Methodology

This was a cross-sectional analytic observational quantitative survey conducted by a team of trained field investigators using a structured observational checklist across 6875 public places in Punjab state of India. The study was carried out over a period of 3 years.

Results

A total of 6875 public places across 22 districts of Punjab were observed. The overall compliance to smoke-free law in Punjab was 83.8%. The highest overall compliance was observed in healthcare facilities (89.6%) and least in transit stations (78.8%). Less active smoking was observed in public places where display of ‘no smoking’ signage compliant with smoke-free law of India was present (adjusted OR 0.6). Further, there was a positive association between active smoking and places where the owner of public places smoked (OR 5.2, CI 2.5 to 11.1).

Conclusion

More than 80% of the public places in a jurisdiction in north India were compliant with the smoke-free legislation of India. ‘No smoking’ signages displayed as per legislation have an effect on curbing smoking behaviours at public places. It is recommended that policymakers should focus more on implementing the smoke-free law at transit sites and structured training sessions should be organised for owners of workplaces.
Co-movement and Forecasting Analysis of Major Real Estate Markets by Wavelet Coherence and Multiple Wavelet Coherence
Authors: KARATAS Cengiz , UNAL Gazanfer , YILMAZ Adil
Published: August 2017

Wavelet coherence of time series provides valuable information about dynamic correlation and its impact on time scales. Here, the authors analyze the wavelet coherence of major real estate markets data, and take the USA, Hong Kong of China, Canada, Japan, and Developed Europe real estate market prices as time series. The wavelet coherence results show relationships among these markets, the correlations between the two and three markets (by multiple wavelet coherence) and how these relationships vary in the time-frequency space. These relationships allow the authors to build VARMA models of real estate data which produce forecasts with small errors.
A Tucker Deep Computation Model for Mobile Multimedia Feature Learning
Authors: Zhang Qingchen , Yang Laurence T. , Liu Xingang , Chen Zhikui , Li Peng
Published: August 2017

Recently, the deep computation model, as a tensor deep learning model, has achieved super performance for multimedia feature learning. However, the conventional deep computation model involves a large number of parameters. Typically, training a deep computation model with millions of parameters needs high-performance servers with large-scale memory and powerful computing units, limiting the growth of the model size for multimedia feature learning on common devices such as portable CPUs and conventional desktops. To tackle this problem, this article proposes a Tucker deep computation model by using the Tucker decomposition to compress the weight tensors in the full-connected layers for multimedia feature learning. Furthermore, a learning algorithm based on the back-propagation strategy is devised to train the parameters of the Tucker deep computation model. Finally, the performance of the Tucker deep computation model is evaluated by comparing with the conventional deep computation model on two representative multimedia datasets, that is, CUAVE and SNAE2, in terms of accuracy drop, parameter reduction, and speedup in the experiments. Results imply that the Tucker deep computation model can achieve a large-parameter reduction and speedup with a small accuracy drop for multimedia feature learning.
The Inherent Asymmetry of DNA Replication
Authors: Snedeker Jonathan , Wooten Matthew , Chen Xin
Published: August 2017

Semiconservative DNA replication has provided an elegant solution to the fundamental problem of how life is able to proliferate in a way that allows cells, organisms, and populations to survive and replicate many times over. Somewhat lost, however, in our admiration for this mechanism is an appreciation for the asymmetries that occur in the process of DNA replication. As we discuss in this review, these asymmetries arise as a consequence of the structure of the DNA molecule and the enzymatic mechanism of DNA synthesis. Increasing evidence suggests that asymmetries in DNA replication are able to play a central role in the processes of adaptation and evolution by shaping the mutagenic landscape of cells. Additionally, in eukaryotes, recent work has demonstrated that the inherent asymmetries in DNA replication may play an important role in the process of chromatin replication. As chromatin plays an essential role in defining cell identity, asymmetries generated during the process of DNA replication may play critical roles in cell fate decisions related to patterning and development.
Do the Effects of Accounting Requirements on Banks’ Regulatory Capital Adequacy Undermine Financial Stability?
Authors: Ryan Stephen G.
Published: August 2017

During the 2007–2009 financial crisis, many parties criticized aspects of accounting requirements for banks as undermining financial stability. These criticisms generally reflect the view that these requirements primarily affect stability through their effects on banks’ regulatory capital adequacy. I criti-cally evaluate whether this idea can be sustained on logical and evidential grounds. I explain how accounting requirements typically have quite small effects on banks’ regulatory capital adequacy. I discuss the plausibility of the alternative view that accounting requirements primarily affect stability by improving banks’ understanding of their risks and their transparency to markets and regulators. Because securitization is the setting in which banks’ regulatory capital adequacy is most likely to be significantly affected by accounting requirements, I describe empirical research on significant changes in securitization accounting effective in 2010. I explain how even in this setting regulatory capital adequacy incompletely explains how accounting requirements for banks affect stability.
Exchange-Traded Funds
Authors: Ben-David Itzhak , Franzoni Francesco , Moussawi Rabih
Published: August 2017

Over nearly a quarter of a century, exchange-traded funds (ETFs) have become one of the most popular passive investment vehicles among retail and professional investors because of their low transaction costs and high liquidity. By the end of 2016, the market share of ETFs exceeded 10% of the total market capitalization traded on US exchanges, representing more than 30% of overall trading volume. ETFs revolutionized the asset management industry by taking market share from traditional investment vehicles such as mutual funds and index futures. Because ETFs rely on arbitrage activity to synchronize their prices with the prices of the underlying portfolio, trading activity at the ETF level translates to trading of the underlying securities. Researchers have found that although ETFs enhance price discovery, they also inject nonfundamental volatility into market prices and affect the correlation structure of returns. Furthermore, ETFs impact the liquidity of the underlying portfolios, especially during events of market stress.
Exercise of obese mice induces cardioprotection and oxygen sparing in hearts exposed to high-fat load
Authors: Boardman Neoma T. , Hafstad Anne D. , Lund Jim , Rossvoll Line , Aasum Ellen
Published: August 2017

Exercise training is a potent therapeutic approach in obesity and diabetes that exerts protective effects against the development of diabetic cardiomyopathy and ischemic injury. Acute increases in circulating fatty acids (FAs) during an ischemic insult can challenge the heart, since high FA load is considered to have adverse cardiac effects. In the present study, we tested the hypothesis that exercise-induced cardiac effects in diet-induced obese mice are abrogated by an acute high FA load. Diet-induced obese mice were fed a high-fat diet (HFD) for 20 wk. They were exercised using moderate- and/or high-intensity exercise training (MIT and HIT, respectively) for 10 or 3 wk, and isolated perfused hearts from these mice were exposed to a high FA load. Sedentary HFD mice served as controls. Ventricular function and myocardial O2 consumption were assessed after 10 wk of HIT and MIT, and postischemic functional recovery and infarct size were examined after 3 wk of HIT. In addition to improving aerobic capacity and reducing obesity and insulin resistance, long-term exercise ameliorated the development of diet-induced cardiac dysfunction. This was associated with improved mechanical efficiency because of reduced myocardial oxygen consumption. Although to a lesser extent, 3-wk HIT also increased aerobic capacity and decreased obesity and insulin resistance. HIT also improved postischemic functional recovery and reduced infarct size. Event upon the exposure to a high FA load, short-term exercise induced an oxygen-sparing effect. This study therefore shows that exercise-induced cardioprotective effects are present under hyperlipidemic conditions and highlights the important role of myocardial energetics during ischemic stress.

NEW & NOTEWORTHY The exercise-induced cardioprotective effects in obese hearts are present under hyperlipidemic conditions, comparable to circulating levels of FA occurring with an ischemic insult. Myocardial oxygen sparing is associated with this effect, despite the general notion that high fat can decrease cardiac efficiency. This highlights the role of myocardial energetics during ischemic stress.
An update on hormone therapy in postmenopausal women: mini-review for the basic scientist
Authors: Miller Virginia M. , Harman S. Mitchell
Published: August 2017

The worlds of observational, clinical, and basic science collided in 2002 with the publication of results of the Women’s Health Initiative (WHI), a large-scale, prospective, blinded, randomized-controlled trial designed to provide evidence regarding use of hormone treatment to prevent cardiovascular disease in menopausal women. The results of the WHI dramatically changed clinical practice, negatively impacted funding for hormone research, and left scientists to unravel the “why” of the results. Now over a decade and a half since the initial publication of the WHI results, basic and clinical scientists often do not interpret the results of the WHI with the precision needed to move the science forward. This review will 1) describe the historical background leading up to the WHI, 2) list the outcomes from the WHI, and put them in perspective with results of subsequent analysis of the WHI data and results from other prospective menopausal hormone treatment trials addressing cardiovascular effects of menopausal hormone use, and 3) articulate how the collective results are influencing current clinical care with the intent to provide guidance for designing and evaluating relevant new hormonal studies.

Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/update-on-hormone-therapy-trials/ .
CYP2E1 regulates the development of radiation-induced pulmonary fibrosis via ER stress- and ROS-dependent mechanisms
Authors: Son Beomseok , Kwon TaeWoo , Lee Sungmin , Han IkJoon , Kim Wanyeon , Youn HyeSook , Youn BuHyun
Published: August 2017

Radiation-induced pulmonary fibrosis (RIPF) is one of the most common side effects of lung cancer radiotherapy. This study was conducted to identify the molecular mechanism responsible for RIPF. We revealed that the transcriptional level of cytochrome P450 2E1 (CYP2E1) was elevated by examining expression profile analysis of RIPF mouse models. We also confirmed that CYP2E1 regulated levels of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in alveolar epithelial type II (AE2) cells and lung fibroblasts. Inhibition of CYP2E1 via its siRNA or inhibitor significantly attenuated epithelial-to-mesenchymal transition and apoptosis of AE2 cells, as well as myofibroblast formation induced by radiation. Finally, the effects of a CYP2E1 inhibitor on development of RIPF were evaluated by in vivo studies. Taken together, the results of the present study suggest that CYP2E1 is an important mediator of RIPF development that functions by increasing cellular ER stress and ROS levels.
Aquaporin 1-mediated changes in pulmonary arterial smooth muscle cell migration and proliferation involve β-catenin
Authors: Yun Xin , Jiang Haiyang , Lai Ning , Wang Jian , Shimoda Larissa A.
Published: August 2017

Exposure to hypoxia induces migration and proliferation of pulmonary arterial smooth muscle cells (PASMCs), leading to vascular remodeling and contributing to the development of hypoxic pulmonary hypertension. The mechanisms controlling PASMC growth and motility are incompletely understood, although aquaporin 1 (AQP1) plays an important role. In tumor, kidney, and stem cells, AQP1 has been shown to interact with β-catenin, a dual function protein that activates the transcription of crucial target genes (i.e., c-Myc and cyclin D1) related to cell migration and proliferation. Thus the goal of this study was to examine mechanisms by which AQP1 mediates PASMC migration and proliferation, with a focus on β-catenin. Using primary rat PASMCs from resistance level pulmonary arteries infected with adenoviral constructs containing green fluorescent protein (control; AdGFP), wild-type AQP1 (AdAQP1), or AQP1 with the COOH-terminal tail deleted (AdAQP1M), we demonstrated that increasing AQP1 expression upregulated β-catenin protein levels and the expression (mRNA and protein) of the known β-catenin targets c-Myc and cyclin D1. In contrast, infection with AdAQP1M had no effect on any of these variables. Using silencing approaches to reduce β-catenin levels prevented both hypoxia- and AQP1-induced migration and proliferation of PASMCs, as well as induction of c-Myc and cyclin D1 by AQP1. Thus our results indicate that elevated AQP1 levels upregulate β-catenin protein levels, via a mechanism requiring the AQP1 COOH-terminal tail, enhancing expression of β-catenin targets and promoting PASMC proliferation and migration.
Remote ischemic preconditioning does not prevent acute mountain sickness after rapid ascent to 3,450 m
Authors: Berger Marc M. , Macholz Franziska , Lehmann Lukas , Dankl Daniel , Hochreiter Marcel , Bacher Bernhard , Bärtsch Peter , Mairbäurl Heimo
Published: August 2017

Remote ischemic preconditioning (RIPC) has been shown to protect remote organs, such as the brain and the lung, from damage induced by subsequent hypoxia or ischemia. Acute mountain sickness (AMS) is a syndrome of nonspecific neurologic symptoms and in high-altitude pulmonary edema excessive hypoxic pulmonary vasoconstriction (HPV) plays a pivotal role. We hypothesized that RIPC protects the brain from AMS and attenuates the magnitude of HPV after rapid ascent to 3,450 m. Forty nonacclimatized volunteers were randomized into two groups. At low altitude (750 m) the RIPC group ( n = 20) underwent 4 × 5 min of lower-limb ischemia (induced by inflation of bilateral thigh cuffs to 200 mmHg) followed by 5 min of reperfusion. The control group ( n = 20) underwent a sham protocol (4 × 5 min of bilateral thigh cuff inflation to 20 mmHg). Thereafter, participants ascended to 3,450 m by train over 2 h and stayed there for 48 h. AMS was evaluated by the Lake Louise score (LLS) and the AMS-C score. Systolic pulmonary artery pressure (SPAP) was assessed by transthoracic Doppler echocardiography. RIPC had no effect on the overall incidence (RIPC: 35%, control: 35%, P = 1.0) and severity (RIPC vs. control: P = 0.496 for LLS; P = 0.320 for AMS-C score) of AMS. RIPC also had no significant effect on SPAP [maximum after 10 h at high altitude; RIPC: 33 (SD 8) mmHg; controls: 37 (SD 7) mmHg; P = 0.19]. This study indicates that RIPC, performed immediately before passive ascent to 3,450 m, does not attenuate AMS and the magnitude of high-altitude pulmonary hypertension.

NEW & NOTEWORTHY Remote ischemic preconditioning (RIPC) has been reported to improve neurologic and pulmonary outcome following an acute ischemic or hypoxic insult, yet the effect of RIPC for protecting from high-altitude diseases remains to be determined. The present study shows that RIPC, performed immediately before passive ascent to 3,450 m, does not attenuate acute mountain sickness and the degree of high-altitude pulmonary hypertension. Therefore, RIPC cannot be recommended for prevention of high-altitude diseases.
Study of β-Glucosidase from Helix pomatia by Active
Site-Directed Inhibitors
Authors: Donsimon R. , Legler G. , Bourbouze R. , Lalegerie P.
Published: August 2017

This work describes the purification of a β-glucosidase (β-D)-glucoside-glucohydrolase
EC 3.2.1.21) from the digestive juice of Helix pomatia and the study of the enzyme’s
active site by using different reversible and irreversible inhibitors. The catalytic constants of
arylglycosides and their pH-dependent variations have also been determined. The inhibition
studies demonstrate that conduritol epoxides are irreversible inhibitors of β-glucosidase
from the digestive juice of H. pomatia, and that nojirimicin shows tight binding with glucosidase:
the formation and dissociation of the enzyme-inhibitor complex (dissociation constant
1.1 μmol/1) required several minutes.
Influence of Cholestyramine Feeding on Mevalonate-Activating Enzymes
Authors: Gonzalez-Pacanowska D. , Marco C. , Iglesias J. , Garcia-Martinez J. , Garcia-Peregrin E.
Published: August 2017

Phosphorylation and decarboxylation of mevalonic acid have been measured in
different tissues of chicks fed a cholestyramine diet from hatching until 18 days of age.
Hepatic and intestinal phosphorylation and decarboxylation of mevalonate were slightly
although significantly increased from 15 days of treatment. Direct measurements of 5-pyrophosphomevalonate
decarboxylase activity using the specific substrate of this enzyme corroborated
these data. Brain enzymatic activities remained unaltered with respect to controls.
These results suggest that enzymes responsible for the conversion of mevalonate to isopentenyl
pyrophosphate from neonatal chick liver and intestine alter their activities in a coordinate
fashion and may play an important role in the regulation of cholesterogenesis in these
tissues.
Genetic Influences on Diagnostic Enzymes in Plasma
Authors: Rosalki Sidney B.
Published: August 2017

Genetic factors which may influence the activity of diagnostic enzymes in
plasma are reviewed. Examples are given of the effects of race, blood group, enzyme polymorphisms,
genetic variants, inborn errors and inherited disease.
Biofunctional Ionic-Doped Calcium Phosphates: Silk Fibroin Composites for Bone Tissue Engineering Scaffolding
Authors: Pina S. , Canadas R.F. , Jiménez G. , Perán M. , Marchal J.A. , Reis R.L. , Oliveira J.M.
Published: August 2017

The treatment and regeneration of bone defects caused by traumatism or diseases have not been completely addressed by current therapies. Lately, advanced tools and technologies have been successfully developed for bone tissue regeneration. Functional scaffolding materials such as biopolymers and bioresorbable fillers have gained particular attention, owing to their ability to promote cell adhesion, proliferation, and extracellular matrix production, which promote new bone growth. Here, we present novel biofunctional scaffolds for bone regeneration composed of silk fibroin (SF) and β-tricalcium phosphate (β-TCP) and incorporating Sr, Zn, and Mn, which were successfully developed using salt-leaching followed by a freeze-drying technique. The scaffolds presented a suitable pore size, porosity, and high interconnectivity, adequate for promoting cell attachment and proliferation. The degradation behavior and compressive mechanical strengths showed that SF/ionic-doped TCP scaffolds exhibit improved characteristics for bone tissue engineering when compared with SF scaffolds alone. The in vitro bioactivity assays using a simulated body fluid showed the growth of an apatite layer. Furthermore, in vitro assays using human adipose-derived stem cells presented different effects on cell proliferation/differentiation when varying the doping agents in the biofunctional scaffolds. The incorporation of Zn into the scaffolds led to improved proliferation, while the Sr- and Mn-doped scaffolds presented higher osteogenic potential as demonstrated by DNA quantification and alkaline phosphatase activity. The combination of Sr with Zn led to an influence on cell proliferation and osteogenesis when compared with single ions. Our results indicate that biofunctional ionic-doped composite scaffolds are good candidates for further in vivo studies on bone tissue regeneration.
Impact of Body Site, Age, and Gender on the Collagen/Elastin Index by Noninvasive in vivo Vertical Two-Photon Microscopy
Authors: Czekalla Carolin , Schönborn Karl-Heinz , Döge Nadine , Jung Sora , Darvin Maxim E. , Lademann Jürgen , Meinke Martina C.
Published: August 2017

Background/Aims: Extrinsic and intrinsic skin aging is subject to constant remodeling and degradation processes, primarily in components of the extracellular matrix. While collagen fibers thin out during the aging process, the amorphous elastin fibers accumulate. These are essential formative components of the dermis. So far, these processes have been detected in vertical histological sections of invasive biopsies and recently in noninvasive horizontal scans. Methods: In this pilot study, a modified noninvasive 2-photon microscope was applied to measure the collagen/elastin index of skin in vivo. The obtained images permit an immediate vertical survey and allow a conclusion on the dermal composition at once. The collagen/elastin index was quantified by the second harmonic to autofluorescence aging index of dermis (SAAID) depending on volunteers' age (18-66 years), gender, and body area. Results: The highest SAAID was measured at the volar forearm as compared to the abdominal SAAID, which was significantly lower (p < 0.05). The gluteal region showed the significantly lowest SAAID (p < 0.05). The SAAID in female skin was higher compared to male skin and decreased with increasing age. Conclusion: These effects are to be considered in subsequent studies to be able to specifically detect and evaluate influences.
Potential Gender-Related Aging Processes Occur Earlier and Faster in the Vermis of Patients with Bipolar Disorder: An MRI Study
Authors: Serati Marta , Delvecchio Giuseppe , Orsenigo Giulia , Perlini Cinzia , Barillari Marco , Ruggeri Mirella , Altamura Alfredo Carlo , Bellani Marcella , Brambilla Paolo
Published: August 2017

Background: In the last decades, there has been increasing interest in investigating the role of the vermis in bipolar disorder (BD), especially because of its involvement in cognitive processes. The main aims of this study were to explore the integrity of the vermis and elucidate the role of demographic and clinical variables on vermis volumes in BD patients, stratified according to gender. Methods: T1-weighted images were obtained for 38 BD patients and 38 healthy controls using a 1.5-T MRI scanner. Images were analyzed with a PC workstation with BRAINS2 software on a Linux system. Anatomical regions were traced manually from a blinded operator, with respect to subject identity and other clinical variables. Results: The direct comparison between the 2 groups showed no significant gray matter differences in vermis volumes. Interestingly, vermis volumes were significantly inversely associated with chronological age and age of BD onset, particularly in male subjects. Conclusions: Our study provides evidence of the impact of aging on the vermis in BD, potentially related to earlier and faster gender-related neurodegenerative phenomena occurring during the progression of the disease.
Gender-Specific Aspects in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation: A Single-Center Experience
Authors: Posch Doris , Rabitsch Werner , Wohlfarth Philipp , Leiner Michael , Porpaczy Edit , Drach Johannes , Raderer Markus , Lamm Wolfgang
Published: August 2017

Objective: Limited data exist on gender-specific aspects in hematologic malignancies and have been obtained mostly in non-Hodgkin lymphomas. The objective of this study was to investigate gender-specific aspects in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). Methods: A retrospective data analysis of 191 patients with MM who underwent ASCT was performed. Data collected from clinical records included age, sex, stage, induction therapy, outcome of induction, kind of stem cell mobilization, response to induction therapy and ASCT, cytogenetic aberrations, progression-free survival, and overall survival. Results: Eighty-one patients (42%) were female, whereas 110 patients were male (58%). No differences between female and male patients could be observed according to the international staging system (ISS) (e.g., ISS III: 14.8 vs. 17.3%), type of paraprotein, and cytogenetic aberrations (e.g., Del(13q): 32.7 vs. 28.9%). Five-year overall survival rates, when calculated from time to ASCT until death, were 27.2 and 36.4% and, when calculated from time to diagnosis until death, were 34.6 and 44.5%, respectively, and did not differ between groups according to ISS subgroups. Conclusion: Prognosis and baseline characteristics were identical and no differences could be observed between female and male patients with MM undergoing ASCT.
ATF3-Dependent Regulation of EGR1 in vitro and in vivo
Authors: Schoen Ilona , Koitzsch Sabine
Published: August 2017

Background/Aims: Activating transcription factor 3 (ATF3) and early growth response protein 1 (EGR1) are reported to interact, but their use as prognostic factors in cancer is discussed controversially. Methods: We measured ATF3 and EGR1 gene expression changes in human mini-organ cultures (MOCs) of healthy nasal epithelia, UM-SCC-22B, and FADUDD cells after acid reflux exposure. Next, ATF3 and EGR1 gene expression was analysed in tumour tissues and related to the median expression of autologous reference tissue samples. Results: ATF3 and EGR1 mRNA expression was significantly reduced after consecutive exposure of MOCs at pH <7.0 to artificial gastric juice (refluxate). In contrast, ATF3 mRNA was upregulated significantly within the first hour of incubation. EGR1 mRNA exhibited no significant changes. The analysed cell lines exhibited a cell line-specific alteration. In FADUDD cells, the upregulation of EGR1 was significant after refluxate exposure, but in HN-SCC 22B, no significant changes were detected. The analysis of the HNSCC samples confirmed the heterogeneous data of the literature. Conclusion: The data maintain the hypothesis that ATF3 and EGR1 are involved in the beginning of inflammatory processes. Whether these two transcription factors act as tumour suppressors or promoters is context dependent and warrants analysis in further studies.
Long-term bleeding risk prediction in ‘real world’ patients with atrial fibrillation: Comparison of the HAS-BLED and ABC-Bleeding risk scores
Authors: Roldán Vanessa , Vicente Vicente , Valdés Mariano , Lip Gregory Y. H. , Asunción Esteve-Pastor María , Miguel Rivera-Caravaca José , Marín Francisco
Published: August 2017

Risk scores in patients with atrial fibrillation (AF) based on clinical factors alone generally have only modest predictive value for predicting high risk patients that sustain events. Biomarkers might be an attractive prognostic tool to improve bleeding risk prediction. The new ABCBleeding score performed better than HAS-BLED score in a clinical trial cohort but has not been externally validated. The aim of this study was to analyze the predictive performance of the ABC-Bleeding score compared to HAS-BLED score in an independent “real-world” anticoagulated AF patients with long-term follow-up. We enrolled 1,120 patients stable on vitamin K antagonist treatment. The HAS-BLED and ABC-Bleeding scores were quantified. Predictive values were compared by c-indexes, IDI, NRI, as well as decision curve analysis (DCA). Median HAS-BLED score was 2 (IQR 2–3) and median ABC-Bleeding was 16.5 (IQR 14.3–18.6). After 6.5 years of follow-up, 207 (2.84%/year) patients had major bleeding events, of which 65 (0.89%/year) had intracranial haemorrhage (ICH) and 85 (1.17%/year) had gastrointestinal bleeding events (GIB). The c-index of HAS-BLED was significantly higher than ABC-Bleeding for major bleeding (0.583 vs 0.518; p=0.025), GIB (0.596 vs 0.519; p=0.017) and for the composite of ICH-GIB (0.593 vs 0.527; p=0.030). NRI showed a significant negative reclassification for major bleeding and for the composite of ICH-GIB with the ABC-Bleeding score compared to HAS-BLED. Using DCAs, the use of HAS-BLED score gave an approximate net benefit of 4% over the ABC-Bleeding score. In conclusion, in the first “real-world” validation of the ABC-Bleeding score, HAS-BLED performed significantly better than the ABC-Bleeding score in predicting major bleeding, GIB and the composite of GIB and ICH.

Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Progression From Esophageal Thermal Asymptomatic Lesion to Perforation Complicating Atrial Fibrillation Ablation
Authors: Halbfass Philipp , Pavlov Borche , Müller Patrick , Nentwich Karin , Sonne Kai , Barth Sebastian , Hamm Karsten , Fochler Franziska , Mügge Andreas , Lüsebrink Ulrich , Kuhn Rainer , Deneke Thomas
Published: August 2017

Background—

Up to 40% of patients demonstrate endoscopically detected asymptomatic esophageal lesions (EDEL) after atrial fibrillation ablation.

Methods and Results—

Patients undergoing first atrial fibrillation ablation and postinterventional esophageal endoscopy were included in the study. Occurrence of esophageal perforating complications during follow-up was related to documented EDEL (category 1: erythema/erosion; category 2: ulcer). In total, 1802 patients underwent first atrial fibrillation ablation procedure between January 2013 and August 2016 at our institution. Out of this group, 832 patients (506 male patients, 61%; 64.0±10.0 years) with symptomatic paroxysmal (n=345; 42%) or persistent atrial fibrillation underwent postprocedural esophageal endoscopy. Patients were ablated using single-tip ablation with conventional or surround flow irrigation and circular ablation catheters with open irrigation (nMARQ). In 295 of 832 patients (35%), a temperature probe was used. EDEL occurred in 150 patients (18%; n=98 category 1 EDEL, n=52 category 2 EDEL). In 5 of 832 patients (0.6%), an esophageal perforation (n=3) or an esophagopericardial or atrioesophageal fistula (n=2) occurred 15 to 28 days (19±6 days) after ablation. Two patients (1 atrioesophageal fistula and 1 esophagopericardial fistula) died. Esophageal perforation occurred only in patients with category 2 lesions (absolute risk, 9.6%). In a logistic regression analysis, ulcers were identified to be a significant predictor for esophageal perforating complications.

Conclusions—

Postablation endoscopy seems to identify patients at high risk of esophageal perforating complications only occurring in patients with category 2 EDEL. One out of 10 postablation esophageal ulcers progressed to perforation, and no patient without esophageal thermal ulcers showed the occurrence of perforating esophageal complications.