bluuebunny/crossref_metadata_2025 huggingface dataset:
An Aminotransferase Is Responsible for the Deamination of the N-Terminal Leucine and Required for Formation of Oxazolone Ring A in Methanobactin of Methylosinus trichosporium OB3b
Authors: Gu Wenyu , Baral Bipin S. , DiSpirito Alan A. , Semrau Jeremy D.
Published: October 2016

Gene expression in methanotrophs has been shown to be affected by the availability of a variety of metals, most notably copper-regulating expression of alternative forms of methane monooxygenase. A copper-binding compound, or chalkophore, called methanobactin plays a key role in copper uptake in methanotrophs. Methanobactin is a ribosomally synthesized and posttranslationally modified peptide (RiPP) with two heterocyclic rings with an associated thioamide for each ring, formed from X-Cys dipeptide sequences that bind copper. The gene coding for the precursor polypeptide of methanobactin,mbnA, is part of a gene cluster, but the role of other genes in methanobactin biosynthesis is unclear. To begin to elucidate the function of these genes, we constructed an unmarked deletion ofmbnABCMNinMethylosinus trichosporiumOB3b and then homologously expressedmbnABCMusing a broad-host-range cloning vector to determine the function ofmbnN, annotated as coding for an aminotransferase. Methanobactin produced by this strain was found to be substantially different from wild-type methanobactin in that the C-terminal methionine was missing and only one of the two oxazolone rings was formed. Rather, in place of the N-terminal 3-methylbutanoyl-oxazolone-thioamide group, a leucine and a thioamide-containing glycine (Gly-Ψ) were found, indicating that MbnN is used for deamination of the N-terminal leucine of methanobactin and that this posttranslational modification is critical for closure of the N-terminal oxazolone ring inM. trichosporiumOB3b. These studies provide new insights into methanobactin biosynthesis and also provide a platform for understanding the function of other genes in the methanobactin gene cluster.

IMPORTANCEMethanotrophs, microbes that play a critical role in the carbon cycle, are influenced by copper, with gene expression and enzyme activity changing as copper levels change. Methanotrophs produce a copper-binding compound, or chalkophore, called methanobactin for copper uptake, and methanobactin plays a key role in controlling methanotrophic activity. Methanobactin has also been shown to be effective in the treatment of Wilson disease, an autosomal recessive disorder where the human body cannot correctly assimilate copper. It is important to characterize the methanobactin biosynthesis pathway to understand how methanotrophs respond to their environment as well as to optimize the use of methanobactin for the treatment of copper-related diseases such as Wilson disease. Here we show thatmbnN, encoding an aminotransferase, is involved in the deamination of the N-terminal leucine and necessary for the formation of one but not both of the heterocyclic rings in methanobactin that are responsible for copper binding.
Inactivation Strategies for Clostridium perfringens Spores and Vegetative Cells
Authors: Talukdar Prabhat K. , Udompijitkul Pathima , Hossain Ashfaque , Sarker Mahfuzur R.
Published: October 2016

Clostridium perfringens
is an important pathogen to human and animals and causes a wide array of diseases, including histotoxic and gastrointestinal illnesses.
C. perfringens
spores are crucial in terms of the pathogenicity of this bacterium because they can survive in a dormant state in the environment and return to being live bacteria when they come in contact with nutrients in food or the human body. Although the strategies to inactivate
C. perfringens
vegetative cells are effective, the inactivation of
C. perfringens
spores is still a great challenge. A number of studies have been conducted in the past decade or so toward developing efficient inactivation strategies for
C. perfringens
spores and vegetative cells, which include physical approaches and the use of chemical preservatives and naturally derived antimicrobial agents. In this review, different inactivation strategies applied to control
C. perfringens
cells and spores are summarized, and the potential limitations and challenges of these strategies are discussed.
Assessment of the implementation fidelity of the Arctic Char Distribution Project in Nunavik, Quebec
Authors: Gautier Lara , Pirkle Catherine M , Furgal Christopher , Lucas Michel
Published: October 2016

Background

In September 2011, the Nunavik Regional Board of Health and Social Services began supporting the Arctic Char Distribution Project (AC/DP) for pregnant women. This initiative promoted consumption of the fish Arctic char—a traditional Inuit food—by pregnant women living in villages of Nunavik, an area in northern Quebec (Canada) inhabited predominantly by people of Inuit ethnicity. This intervention was intended to reduce exposure to contaminants and improve food security in Inuit communities.

Methods

We assessed the project's implementation based on data collected from background documentation, field notes and qualitative interviews with project recipients and implementers. Themes emerging from the data are critically discussed in the light of the framework for implementation fidelity developed by Carrollet alin 2007.

Results

Pregnant women fully embraced the initiative because of its cultural appropriateness. However, project implementation was incomplete: first because it did not cover all intended geographic areas, and second because of a recurring inconsistency in the supply and distribution of the fish. In addition, the initiative has been inconsistently funded and relies on multiple funding sources.

Discussion

This work highlights the extent to which project complexity can impede successful implementation, particularly in terms of communication and coordination. We provide recommendations for improving project implementation and suggest amendments to the implementation fidelity framework.
Realist synthesis of educational interventions to improve nutrition care competencies and delivery by doctors and other healthcare professionals
Authors: Mogre Victor , Scherpbier Albert J J A , Stevens Fred , Aryee Paul , Cherry Mary Gemma , Dornan Tim
Published: October 2016

Objective

To determine what, how, for whom, why, and in what circumstances educational interventions improve the delivery of nutrition care by doctors and other healthcare professionals work.

Design

Realist synthesis following a published protocol and reported following Realist and Meta-narrative Evidence Synthesis: Evolving Standards (RAMESES) guidelines. A multidisciplinary team searched MEDLINE, CINAHL, ERIC, EMBASE, PsyINFO, Sociological Abstracts, Web of Science, Google Scholar and Science Direct for published and unpublished (grey) literature. The team identified studies with varied designs; appraised their ability to answer the review question; identified relationships between contexts, mechanisms and outcomes (CMOs); and entered them into a spreadsheet configured for the purpose. The final synthesis identified commonalities across CMO configurations.

Results

Over half of the 46 studies from which we extracted data originated from the USA. Interventions that improved the delivery of nutrition care improved skills and attitudes rather than just knowledge; provided opportunities for superiors to model nutrition care; removed barriers to nutrition care in health systems; provided participants with local, practically relevant tools and messages; and incorporated non-traditional, innovative teaching strategies. Operating in contexts where student and qualified healthcare professionals provided nutrition care in developed and developing countries, these interventions yielded health outcomes by triggering a range of mechanisms, which included feeling competent, feeling confident and comfortable, having greater self-efficacy, being less inhibited by barriers in healthcare systems and feeling that nutrition care was accepted and recognised.

Conclusions

These findings show how important it is to move education for nutrition care beyond the simple acquisition of knowledge. They show how educational interventions embedded within systems of healthcare can improve patients’ health by helping health students and professionals to appreciate the importance of delivering nutrition care and feel competent to deliver it.
Does angiography increase the risk of impairment in renal function during non-operative management of patients with blunt splenic injuries? A cross-sectional study in southern Taiwan
Authors: Hsieh Ting-Min , Tsai Tzu-Hsien , Lin Chih-Che , Hsieh Ching-Hua
Published: October 2016

Objectives

The aim of the present study was to assess whether angiography after contrast-enhanced CT (CECT) as per the policy of non-operative management would add to the risk of acute kidney injury in patients with blunt splenic injuries (BSIs).

Design

Cross-sectional study.

Setting

Taiwan.

Participants

Patients with BSI aged >16 years, admitted to a level I trauma centre during the period of January 2004 to December 2014, were retrospectively reviewed. A total of 326 patients with BSI with CECT were included in the study, of whom 100 underwent subsequent angiography and 226 did not.

Main outcome measures

Incidence of contrast-induced nephropathy (CIN) and renal function as measured by the 48-hour serum creatinine (SCr) levels.

Results

No significant difference between the patients who underwent angiography and those who did not in terms of the initial haemoglobin (Hb), SCr or estimated glomerular filtration rate (eGFR) level on arrival at the emergency department, 48 hours later, or at discharge. No significant difference in the incidence of CIN was found between these two groups of patients regardless of the criteria for identifying CIN. In the group of patients aged ≥55 years, those who underwent angiography had a significantly worse 48-hour SCr level than those who did not undergo the treatment. In addition, there was no significant difference in the 48-hour SCr level between the two groups of patients when subgrouping the patients according to sex, large haemoperitoneum revealed on CT, systolic blood pressure, initial Hb, initial SCr and initial eGFR levels.

Conclusions

This study demonstrated that angiography does not increase the incidence of CIN, and was not a risk factor to renal function impairment in patients with BSI who had undergone CECT.
Registry-based analysis of participator representativeness: a source of concern for sickness absence research?
Authors: Knapstad Marit , Löve Jesper , Holmgren Kristina , Hensing Gunnel , Øverland Simon
Published: October 2016

Objectives

Selective participation can bias results in epidemiological surveys. The importance of health status is often suggested as a possible explanation for non-participation but few empirical studies exist. In a population-based study, explicitly focused on sickness absence, health and work, we examined whether a history of high levels of sickness absence was associated with non-participation.

Design

The study is based on data from official sickness absence registers from participants, non-participants and the total target population of the baseline survey of the Health Assets Project (HAP).

Setting

HAP is a population-based cohort study in the Västra Götaland region in South Western Sweden.

Participants

HAP included a random population cohort (n=7984) and 2 cohorts with recent sickness absence (employees (n=6140) and non-employees (n=990)), extracted from the same overall general working-age population.

Primary outcome measures

We examined differences in participation rates between cohorts (2008), and differences in previous sickness absence (2001–2008) between participants (individual-level data) and non-participants or the target population (group-level data) within cohorts.

Results

Participants had statistically significant less registered sickness absence in the past than non-participants and the target population for some, but not all, of the years analysed. Yet these differences were not of substantial size. Other factors than sickness absence were more important in explaining differences in participation, whereby participants were more likely to be women, older, born in Nordic countries, married and have higher incomes than non-participants.

Conclusions

Although specifically addressing sickness absence, having such experience did not add any substantial layer to selective participation in the present survey. Detailed measures are needed to gain a better understanding for health selection in health-related surveys such as those addressing sickness absence, for instance in order to discriminate between selection due to ability or motivation for participation.
Protocol for a between-group experimental study examining cultural differences in emotion processing between Malay and Caucasian adults with and without major depressive disorder
Authors: Mohan S N , Mukhtar F , Jobson L
Published: October 2016

Introduction

Depression is a mood disorder that affects a significant proportion of the population worldwide. In Malaysia and Australia, the number of people diagnosed with depression is on the rise. It has been found that impairments in emotion processing and emotion regulation play a role in the development and maintenance of depression. This study is based on Matsumoto and Hwang's biocultural model of emotion and Triandis' Subjective Culture model. It aims to investigate the influence of culture on emotion processing among Malaysians and Australians with and without major depressive disorder (MDD).

Methods and analysis

This study will adopt a between-group design. Participants will include Malaysian Malays and Caucasian Australians with and without MDD (N=320). There will be four tasks involved in this study, namely: (1) the facial emotion recognition task, (2) the biological motion task, (3) the subjective experience task and (4) the emotion meaning task. It is hypothesised that there will be cultural differences in how participants with and without MDD respond to these emotion tasks and that, pan-culturally, MDD will influence accuracy rates in the facial emotion recognition task and the biological motion task.

Ethics and dissemination

This study is approved by the Universiti Putra Malaysia Research Ethics Committee (JKEUPM) and the Monash University Human Research Ethics Committee (MUHREC). Permission to conduct the study has also been obtained from the National Medical Research Register (NMRR; NMRR-15-2314-26919). On completion of the study, data will be kept by Universiti Putra Malaysia for a specific period of time before they are destroyed. Data will be published in a collective manner in the form of journal articles with no reference to a specific individual.
The Screen-ICD trial. Screening for anxiety and cognitive therapy intervention for patients with implanted cardioverter defibrillator (ICD): a randomised controlled trial protocol
Authors: Berg Selina Kikkenborg , Herning Margrethe , Svendsen Jesper Hastrup , Christensen Anne Vinggaard , Thygesen Lau Caspar
Published: October 2016

Introduction

Previous research shows that patients with an implanted cardioverter defibrillator (ICD) have a fourfold increased mortality risk when suffering from anxiety compared with ICD patients without anxiety. This research supports the screening of ICD patients for anxiety with the purpose of starting relevant intervention.

Methods and analysis

Screen-ICD consists of 3 parts: (1) screening of all hospitalised and outpatient patients at two university hospitals using the Hospital Anxiety and Depression Scale (HADS), scores ≥8 are invited to participate. (2) Assessment of type of anxiety by Structured Clinical Interview for DSM Disorders (SCID). (3) Investigator-initiated randomised clinical superiority trial with blinded outcome assessment, with 1:1 randomisation to cognitive–behavioural therapy (CBT) performed by a cardiac nurse with CBT training, plus usual care or usual care alone. The primary outcome is HADS-A measured at 16 weeks. Secondary outcomes include Becks Anxiety Inventory, HeartQoL, Hamilton Anxiety Scale, heart rate variability, ICD shock, time to first shock and antitachycardia pacing. A total of 88 participants will be included. The primary analyses are based on the intention-to-treat principle and we use a mixed model with repeated measurements for continuous outcomes. For binary outcomes (HADS-A score <8), we use a generalised mixed model with repeated measurements.

Ethics and dissemination

The trial is performed in accordance with the Declaration of Helsinki. All patients must give informed consent prior to participation and the trial is initiated after approval by the Danish Data Protection Agency (RH-2015-282) and the regional ethics committee (H-16018868). Positive, neutral and negative results of the trial will be published.

Trial registration number

NCT02713360.
Factors that influence career progression among postdoctoral clinical academics: a scoping review of the literature
Authors: Ranieri Veronica , Barratt Helen , Fulop Naomi , Rees Geraint
Published: October 2016

Background

The future of academic medicine is uncertain. Concerns regarding the future availability of qualified and willing trainee clinical academics have been raised worldwide. Of significant concern is our failure to retain postdoctoral trainee clinical academics, who are likely to be our next generation of leaders in scientific discovery.

Objectives

To review the literature about factors that may influence postdoctoral career progression in early career clinical academics.

Design

This study employed a scoping review method. Three reviewers separately assessed whether the articles found fit the inclusion criteria.

Data sources

PubMed, Scopus, Web of Science and Google Scholar (1991–2015).

Article selection

The review encompassed a broad search of English language studies published anytime up to November 2015. All articles were eligible for inclusion, including research papers employing either quantitative or qualitative methods, as well as editorials and other summary articles.

Data extraction

Data extracted from included publications were charted according to author(s), sample population, study design, key findings, country of origin and year of publication.

Results

Our review identified 6 key influences: intrinsic motivation, work–life balance, inclusiveness, work environment, mentorship and availability of funding. It also detected significant gaps within the literature about these influences.

Conclusions

Three key steps are proposed to help support postdoctoral trainee clinical academics. These focus on ensuring that researchers feel encouraged in their workplace, involved in collaborative dialogue with key stakeholders and able to access reliable information regarding their chosen career pathway. Finally, we highlight recommendations for future research.
Procedural sedation in the emergency department by Dutch emergency physicians: a prospective multicentre observational study of 1711 adults
Authors: Smits Gaël JP , Kuypers Maybritt I , Mignot Lisette AA , Reijners Eef PJ , Oskam Erick , Van Doorn Karen , Thijssen Wendy AMH , Korsten Erik HM
Published: October 2016

Objective

To describe our experience performing ED procedural sedation in a country where emergency medicine (EM) is a relatively new specialty.

Methods

This is a prospective observational study of adult patients undergoing procedural sedation by emergency physicians (EPs) or EM residents in eight hospitals in the Netherlands. Data were collected on a standardised form, including patient characteristics, sedative and analgesic used, procedural success, adverse events (classified according to World SIVA) and rescue interventions.

Results

1711 adult cases were included from 2006 to 2013. Propofol, midazolam and esketamine (S+ enantiomer of ketamine) were the most used sedatives (63%, 29% and 8%). We had adverse event data on all patients. The overall adverse event rate was 11%, mostly hypoxia or apnoea. There was no difference in adverse event rate between EPs and EM residents. However, there was a significantly higher success rate of the procedure when EPs did the procedural sedation (92% vs 84%). No moderate (unplanned hospital admission or escalation of care) or sentinel SIVA outcomes occurred (pulmonary aspiration syndrome, death or permanent neurological deficit).

Conclusion

Adverse events during procedural sedation occurred in 11% of patients. There were no moderate or sentinel outcomes. All events could be managed by the sedating physician. In a country where EM is a relatively new specialty, procedural sedation appears to be safe when performed by EPs or trained EM residents and has comparable adverse event rates to international studies.
Association of Chronic Obstructive Pulmonary Disease and Postresection Lung Cancer Survival: A Systematic Review and Meta-Analysis
Authors: Tan Lan-Eng , Razak AM , Lim Chor-Shen
Published: October 2016

Patients with lung cancer often have chronic obstructive pulmonary disease (COPD), but the impact of COPD on postresection survival of patients with lung cancer is unclear. This study evaluated the impact of COPD on survival of patients with lung cancer following pulmonary resection. Databases searched included PubMed, Cochrane, and Embase until March 2016. Study outcomes were overall survival and pulmonary complication rate (pneumonia, bronchial fistula, and prolonged mechanical ventilation). 6 studies with a total of 3761 patients were included. The presence of COPD was associated with lower overall survival, increased frequency of pneumonia, and prolonged mechanical ventilation (p values ≤0.001). COPD had no influence on bronchial fistula development (p=0.098). In summary, COPD was associated with poorer survival and an increased frequency of certain adverse events in patients with lung cancer following resection.
Early angiographic signs of acute thrombus formation following cerebral aneurysm treatment with the Pipeline embolization device
Authors: Patel Akil , Miller Timothy R , Shivashankar Ravi , Jindal Gaurav , Gandhi Dheeraj
Published: October 2016

Background and objective

Acute thrombus formation following aneurysm treatment with the Pipeline embolization device (PED) is a potentially devastating complication that may result in significant thromboembolic sequelae if not promptly treated. We therefore evaluated PED cases complicated by acute thrombus formation at our institution, with an emphasis on identifying early angiographic signs that may portend this event.

Materials and methods

We retrospectively identified cases of acute thrombosis following PED placement in 100 consecutive procedures performed at our institution from a prospectively maintained clinical database. Angiographic findings were analyzed for early signs of acute thrombus formation. We also evaluated the efficacy of treatment of this complication with a glycoprotein IIb/IIIa inhibitor (abciximab), as well as the results of pre-procedure platelet inhibition testing.

Results

Acute thrombus formation was encountered in five patients following PED placement (5%). Early angiographic signs were present in all cases and included progressive stagnation of blood flow in covered side branches, occlusion of covered side branches, excessive stagnation of blood flow in the target aneurysm, as well as occlusion of the target aneurysm. These sequelae completely resolved following abciximab treatment in all five cases, with no permanent neurological morbidity or mortality. Four of the five patients had a pre-procedure P2Y12 value >200 (range 201–227).

Conclusions

Progressive stagnation or occlusion of covered side branches or target aneurysm are early angiographic signs of acute thrombus formation following PED placement and should prompt immediate treatment with a glycoprotein IIb/IIIa inhibitor. Platelet inhibition testing may help identify those patients who are at an increased risk for this complication.
Severe otitis and pneumonia in adult cattle with mixed infection of Mycoplasma bovis and Mycoplasma agalactiae
Authors: Catania Salvatore , Gobbo Federica , Schiavon Eliana , Nicholas Robin A. J.
Published: October 2016

Respiratory disease and otitis were seen on a northern Italian farm in weaned bulls obtained from multiple sources. Mycoplasma bovis was consistently identified in nasal swabs, tonsil, ears, eyes and lung samples from affected animals. Unusually the closely related Mycoplasma agalactiae, the main cause of contagious agalactia (CA) in small ruminants, was also isolated. It was identified by molecular methods in bulls but only from eye, ear and brain samples. Outbreaks were reduced by retaining the bulls on their original farms for weaning, then moving them directly to the fattening areas on the farm. This prevented the spread of mycoplasma from infected to uninfected calves from different sources. As no small ruminants were within close proximity and the area is free of CA, it is possible that M agalactiae may be more prevalent in cattle than previously thought.
Tripled fixed point theorems and applications to a fractional differential equation boundary value problem
Authors: Afshari Hojjat , Kheiryan Alireza
Published: October 2016

In this article we study a class of mixed monotone operators with convexity on ordered Banach spaces and present some new tripled fixed point theorems by means of partial order theory, we get the existence and uniqueness of tripled fixed points without assuming the operator to be compact or continuous, which extend the existing corresponding results. As applications, we utilize the results obtained in this paper to study the existence and uniqueness of positive solutions for a fractional differential equation boundary value problem.
Visualization framework for CAVE virtual reality systems
Authors: Kageyama Akira , Tomiyama Asako
Published: October 2016

We have developed a software framework for scientific visualization in immersive-type, room-sized virtual reality (VR) systems, or Cave automatic virtual environment (CAVEs). This program, called Multiverse, allows users to select and invoke visualization programs without leaving CAVE’s VR space. Multiverse is a kind of immersive “desktop environment” for users, with a three-dimensional graphical user interface. For application developers, Multiverse is a software framework with useful class libraries and practical visualization programs as samples.
Tempo Driven Audio-to-Score Alignment Using Spectral Decomposition and Online Dynamic Time Warping
Authors: Rodriguez-Serrano Francisco Jose , Carabias-Orti Julio Jose , Vera-Candeas Pedro , Martinez-Munoz Damian
Published: October 2016

In this article, we present an online score following framework designed to deal with automatic accompaniment. The proposed framework is based on spectral factorization and online Dynamic Time Warping (DTW) and has two separated stages: preprocessing and alignment. In the first one, we convert the score into a reference audio signal using a MIDI synthesizer software and we analyze the provided information in order to obtain the spectral patterns (i.e., basis functions) associated to each score unit. In this work, a score unit represents the occurrence of concurrent or isolated notes in the score. These spectral patterns are learned from the synthetic MIDI signal using a method based on Non-negative Matrix Factorization (NMF) with Beta-divergence, where the gains are initialized as the ground-truth transcription inferred from the MIDI. On the second stage, a non-iterative signal decomposition method with fixed spectral patterns per score unit is used over the magnitude spectrogram of the input signal resulting in a distortion matrix that can be interpreted as the cost of the matching for each score unit at each frame. Finally, the relation between the performance and the musical score times is obtained using a strategy based on online DTW, where the optimal path is biased by the speed of interpretation. Our system has been evaluated and compared to other systems, yielding reliable results and performance.
SPMPool
Authors: Tajik Hossein , Donyanavard Bryan , Dutt Nikil , Jahn Janmartin , Henkel Jörg
Published: October 2016

Distributed Scratchpad Memories (SPMs) in embedded many-core systems require careful selection of data placement to achieve good performance. Applications mapped to these platforms have varying memory requirements based on their runtime behavior, resulting in under- or overutilization of the local SPMs. We propose SPMPool to share the available on-chip SPMs on many-cores among concurrently executing applications in order to reduce the overall memory access latency. By pooling SPM resources, we can assign underutilized memory resources, due to idle cores or low memory usage, to applications dynamically. SPMPool is the first workload-aware SPM mapping solution for many-cores that dynamically allocates data at runtime—using profiled data—to address the unpredictable set of concurrently executing applications. Our experiments on workloads with varying interapplication memory intensity show that SPMPool can achieve up to 76% reduction in memory access latency for configurations ranging from 16 to 256 cores, compared to the traditional approach that limits executing cores to use their local SPMs.
Parental vitamin D deficiency during pregnancy is associated with increased blood pressure in offspring viaPanx1hypermethylation
Authors: Meems Laura M. G. , Mahmud Hasan , Buikema Hendrik , Tost Jörg , Michel Sven , Takens Janny , Verkaik-Schakel Rikst N. , Vreeswijk-Baudoin Inge , Mateo-Leach Irene V. , van der Harst Pim , Plösch Torsten , de Boer Rudolf A.
Published: October 2016

Vitamin D deficiency is one of the most common nutritional deficiencies worldwide. Maternal vitamin D deficiency is associated with increased susceptibility to hypertension in offspring, but the reasons for this remain unknown. The aim of this study was to determine if parental vitamin D deficiency leads to altered DNA methylation in offspring that may relate to hypertension. Male and female Sprague-Dawley rats were fed a standard or vitamin D-depleted diet. After 10 wk, nonsibling rats were mated. The conceived pups received standard chow. We observed an increased systolic and diastolic blood pressure in the offspring from depleted parents (F1-depl). Genome-wide methylation analyses in offspring identified hypermethylation of the promoter region of the Pannexin-1 ( Panx1) gene in F1-depl rats. Panx1 encodes a hemichannel known to be involved in endothelial-dependent relaxation, and we demonstrated that in F1-depl rats the increase in blood pressure was associated with impaired endothelial relaxation of the large vessels, suggesting an underlying biological mechanism of increased blood pressure in children from parents with vitamin deficiency. Parental vitamin D deficiency is associated with epigenetic changes and increased blood pressure levels in offspring.
Estrogen receptor antagonism exacerbates cardiac structural and functional remodeling in female rats
Authors: El Hajj M. C. , Ninh V. K. , El Hajj E. C. , Bradley J. M. , Gardner J. D.
Published: October 2016

We have previously demonstrated the cardioprotective effects of ovarian hormones against adverse ventricular remodeling imposed by chronic volume overload. Here, we assess the estrogen receptor dependence of this cardioprotection. Four groups of female rats were studied: sham-operated (Sham), volume overloaded [aortocaval fistula (ACF)], Sham treated with estrogen receptor antagonist ICI 182,780 (Sham + ICI), and ACF treated with ICI. Cardiac function was assessed temporally using echocardiogram, and tissue samples were collected at 5 days and 6 wk postsurgery. All rats with volume overload had significantly increased cardiac output (96 ± 32 ml/min for ACF and 108 ± 11 ml/min for ACF + ICI vs. 31 ± 2 for Sham, P < 0.05). At 6 wk, volume overload induced significant left ventricular (LV) hypertrophy in both untreated and treated ACF groups. Both ACF groups developed significantly increased LV end-diastolic diameter (LVEDD), indicating LV dilatation, with the ACF + ICI group having the greatest increase (340%, relative to Sham). Ejection fraction was significantly reduced in the ACF + ICI group (23% reduction) at 6 wk postsurgery compared with untreated ACF ( P < 0.05). Interstitial collagen staining was significantly reduced by volume overload, with estrogen receptor antagonism causing greater collagen loss at both 5 days and 6 wk postsurgery. Furthermore, volume overload induced a significant increase in LV wall stress only in rats treated with estrogen antagonist. These data indicate that estrogen receptor signaling is essential for sex hormone-dependent cardioprotection against adverse remodeling. The maintenance of myocardial extracellular matrix collagen appears to play a key role in this cardioprotection.

NEW & NOTEWORTHY We assessed the estrogen receptor (ER) dependence of female-specific cardioprotection using a rat model of chronic volume-overload stress. ER antagonism worsened ventricular wall stress, ventricular dilation, and cardiac dysfunction induced by volume overload. Further, blocking ERs resulted in cardiac remodeling and functional changes similar to that previously found in ovariectomized rats.
Exaggerated coronary vasoconstriction limits muscle metaboreflex-induced increases in ventricular performance in hypertension
Authors: Spranger Marty D. , Kaur Jasdeep , Sala-Mercado Javier A. , Krishnan Abhinav C. , Abu-Hamdah Rania , Alvarez Alberto , Machado Tiago M. , Augustyniak Robert A. , O’Leary Donal S.
Published: October 2016

Increases in myocardial oxygen consumption during exercise mainly occur via increases in coronary blood flow (CBF) as cardiac oxygen extraction is high even at rest. However, sympathetic coronary constrictor tone can limit increases in CBF. Increased sympathetic nerve activity (SNA) during exercise likely occurs via the action of and interaction among activation of skeletal muscle afferents, central command, and resetting of the arterial baroreflex. As SNA is heightened even at rest in subjects with hypertension (HTN), we tested whether HTN causes exaggerated coronary vasoconstriction in canines during mild treadmill exercise with muscle metaboreflex activation (MMA; elicited by reducing hindlimb blood flow by ~60%) thereby limiting increases in CBF and ventricular performance. Experiments were repeated after α1-adrenergic blockade (prazosin; 75 µg/kg) and in the same animals following induction of HTN (modified Goldblatt 2K1C model). HTN increased mean arterial pressure from 97.1 ± 2.6 to 132.1 ± 5.6 mmHg at rest and MMA-induced increases in CBF, left ventricular dP/d tmax, and cardiac output were markedly reduced to only 32 ± 13, 26 ± 11, and 28 ± 12% of the changes observed in control. In HTN, α1-adrenergic blockade restored the coronary vasodilation and increased in ventricular function to the levels observed when normotensive. We conclude that exaggerated MMA-induced increases in SNA functionally vasoconstrict the coronary vasculature impairing increases in CBF, which limits oxygen delivery and ventricular performance in HTN.

NEW & NOTEWORTHY We found that metaboreflex-induced increases in coronary blood flow and ventricular contractility are attenuated in hypertension. α1-Adrenergic blockade restored these parameters toward normal levels. These findings indicate that the primary mechanism mediating impaired metaboreflex-induced increases in ventricular function in hypertension is accentuated coronary vasoconstriction.

Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/metaboreflex-induced-functional-coronary-vasoconstriction/ .
Influencing the Tumor Microenvironment: A Phase II Study of Copper Depletion Using Tetrathiomolybdate in Patients with Breast Cancer at High Risk for Recurrence and in Preclinical Models of Lung Metastases
Authors: Chan Nancy , Willis Amy , Kornhauser Naomi , Ward Maureen M. , Lee Sharrell B. , Nackos Eleni , Seo Bo Ri , Chuang Ellen , Cigler Tessa , Moore Anne , Donovan Diana , Vallee Cobham Marta , Fitzpatrick Veronica , Schneider Sarah , Wiener Alysia , Guillaume-Abraham Jessica , Aljom Elnaz , Zelkowitz Richard , Warren J. David , Lane Maureen E. , Fischbach Claudia , Mittal Vivek , Vahdat Linda
Published: October 2016

Purpose: Bone marrow–derived progenitor cells, including VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent pathways, model the tumor microenvironment. We hypothesized that copper depletion using tetrathiomolybdate would reduce EPCs in high risk for patients with breast cancer who have relapsed. We investigated the effect of tetrathiomolybdate on the tumor microenvironment in preclinical models.

Experimental Design: Patients with stage II triple-negative breast cancer (TNBC), stage III and stage IV without any evidence of disease (NED), received oral tetrathiomolybdate to maintain ceruloplasmin (Cp) between 8 and 17 mg/dL for 2 years or until relapse. Endpoints were effect on EPCs and other biomarkers, safety, event-free (EFS), and overall survival (OS). For laboratory studies, MDA-LM2-luciferase cells were implanted into CB17-SCID mice and treated with tetrathiomolybdate or water. Tumor progression was quantified by bioluminescence imaging (BLI), copper depletion status by Cp oxidase levels, lysyl oxidase (LOX) activity by ELISA, and collagen deposition.

Results: Seventy-five patients enrolled; 51 patients completed 2 years (1,396 cycles). Most common grade 3/4 toxicity was neutropenia (3.7%). Lower Cp levels correlated with reduced EPCs (P = 0.002) and LOXL-2 (P < 0.001). Two-year EFS for patients with stage II–III and stage IV NED was 91% and 67%, respectively. For patients with TNBC, EFS was 90% (adjuvant patients) and 69% (stage IV NED patients) at a median follow-up of 6.3 years, respectively. In preclinical models, tetrathiomolybdate decreased metastases to lungs (P = 0.04), LOX activity (P = 0.03), and collagen crosslinking (P = 0.012).

Conclusions: Tetrathiomolybdate is safe, well tolerated, and affects copper-dependent components of the tumor microenvironment. Biomarker-driven clinical trials in high risk for patients with recurrent breast cancer are warranted.
Human Microbiome Fusobacterium Nucleatum in Esophageal Cancer Tissue Is Associated with Prognosis
Authors: Yamamura Kensuke , Baba Yoshifumi , Nakagawa Shigeki , Mima Kosuke , Miyake Keisuke , Nakamura Kenichi , Sawayama Hiroshi , Kinoshita Koichi , Ishimoto Takatsugu , Iwatsuki Masaaki , Sakamoto Yasuo , Yamashita Yoichi , Yoshida Naoya , Watanabe Masayuki , Baba Hideo
Published: October 2016

Purpose: Fusobacterium nucleatum (F. nucleatum) is a component of the human microbiome that primarily inhabits the oral cavity. It causes periodontal disease and has also been implicated in the development of human cancers. Although there are several reports of the relationship between F. nucleatum and the clinical outcome in human cancers, its prognostic significance in esophageal cancer remains unclear.

Experimental Design: We quantified F. nucleatum DNA in 325 resected esophageal cancer specimens by qPCR. Significant pathways in F. nucleatum–positive esophageal cancer tissues were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using microarray data.

Results: Esophageal cancer tissues contained significantly more F. nucleatum DNA than matched normal esophageal mucosa (P = 0.021; n = 60). F. nucleatum DNA was detected in 74 of 325 cases (23%). F. nucleatum DNA positivity was significantly associated with tumor stage, but not with sex, age, performance status, tobacco use, alcohol use, histology, tumor location, or preoperative treatment. F. nucleatum DNA positivity was also significantly associated with cancer-specific survival [log-rank P = 0.0039; univariate HR = 2.01; 95% confidence interval (CI), 1.22–3.23; P = 0.0068; multivariate HR = 1.78; 95% CI, 1.06–2.94; P = 0.031]. The top-ranked KEGG pathway in F. nucleatum–positive tissues was “cytokine–cytokine receptor interaction.” A significant relationship between F. nucleatum and the chemokine CCL20 was validated by IHC.

Conclusions: F. nucleatum in esophageal cancer tissues was associated with shorter survival, suggesting a potential role as a prognostic biomarker. F. nucleatum might also contribute to aggressive tumor behavior through activation of chemokines, such as CCL20. Clin Cancer Res; 22(22); 5574–81. ©2016 AACR.
A Hybrid Methodology for Performance Assessment of Campus Network
Authors: Mao Li , Qi De-yu
Published: October 2016

In this paper, we propose a combined methodology of fuzzy analytic hierarchy process (FAHP) and data envelopment analysis (DEA) in order to apply it to multivariate analysis and integrated evaluation. With FAHP method, the relative importance levels of different available indicators are determined. And the DEA model is used to obtain the efficiency performances of the use case of network measurement. Finally network performance is evaluated by means of integrating available indicator weights with efficiency performances. It is quite important that the integrated methodology considers both personal preferences and objective relative efficiency for assessment simultaneously to avoid the bias of single methodology.
Reliability Evaluation of Wind Turbine Systems’ Components
Authors: Miryousefi Aval Seyed Mohsen , Ahadi Amir
Published: October 2016

The increasing use of wind generation requests modifications in the electric power systems planning conception, because it includes one more uncertainty component, which needs to be studied properly and modeled. Understanding the failures rates and downtimes of wind turbines is difficult not only because of the considerable range of designs and sizes that are now in service worldwide but also since studies are conducted independently under various operating conditions in different countries. The fault tree method (FTA) has been used to study the reliability of many different power generation systems. This paper now applies that method to a wind turbine system to estimate the reliability of wind turbines. In the implementations, several types of wind turbines were considered in order to analyze the system’s reliability. The effectiveness of the proposed method is revealed through several case studies.
Development of Emulation Network Analyzer Tool for Computer Network Planning
Authors: Ismail Mohd Nazri , Zin Abdullah Mohd
Published: October 2016

This paper describes the development of Emulation Network Analyzer (ENA) for heterogeneous services in campus environment. The purpose of this paper is to inform this ENA able to plan and predict network performance. For this purpose, our ENA development is differ from others system such as application and hardware network analyzer. This study focuses on the design of emulation network analyzer, user interface design, characteristics, model description, implementation and evaluation. This ENA can provide a useful network architectural solutions and optimization of network resources during preparation, proposal and planning phases. Finally, ENA tool is a good emulation analyzer that can be used in small to medium size networks for campus environment purposes with minimum cost.
THE CHANGES OF GLIAL FIBRILLARY ACID PROTEIN LEVEL IN THE DIFFERENT BRAIN AREAS OF GERBILS UNDER DEVELOPMENT, AGING AND ALPHA-KETO GLUTARATE EFFECT
Authors: Kovalchuk Yu. P. , Ushakovа H. O.
Published: October 2016

There has been shown the change of level of astrocytes-specific glial fibrillary acid protein (GFAP) in different areas of the brain of laboratory gerbils at different stages of postnatal development, aging, and the effect of lphaketoglutarate.Studies have shown that the content of both soluble and filament forms of GFAP significantly increased during the first 30 days of postnatal development in all parts of the brain. After 30 days, the level of soluble forms of GFAP continued gradualy increase in all studied brain areas of gerbils during development and aging. Content of filament forms of GFAP in the gerbils brain after 90 days has a different tendency to change depending on the brain region. The long-term diet containing 2% alpha-ketoglutarate has been prevented overproduction of filament form of GFAP in the thalamus and hippocampus of older animals.
The research of physical and chemical, antimicrobial qualities of “Decamethoxin®” remedy
Authors: Paliy H. K. , Nazarchuk O. A. , Honchar O. O. , Kovalenko I. V. , Yatsula O. V.
Published: October 2016

In the article there were presented the results of the research of medical physical and chemical qualities of domestic remedy “Decamethoxin®” (Decamethoxinum®), produced by Pilot Manufacturing of Institute of Organic Chemistry of National Academy of Sciences of Ukraine. It was found, that “Decamethoxin®” (DC M) remedy complies physical and chemical requirements (color, transmittance, specific optical rotation, entertainable amount of impurities, sulfate ash, heavy metals, residual amounts of organic substances, the loss of the weight no more than 4.5 %, while desiccation), established for patented exemplar of decamethoxin®. Kinetics of DCM® elution into water medium from medical materials was proved. There was found, that elution of DCM® proceeded long (for 15 days), it was like programmed controlled process, occurring due to diffusion and kinetic mechanisms.
Changes of lipid peroxidation and antioxidant protection in spontaneously hypertensive rats during experimental treatment by Ramipril and Candesartan
Authors: Marushchak A. V. , Shorikov Ye. I. , Shorikova D. V. , Tymofiychuk I. R. , Haydychuk V. S.
Published: October 2016

This article talks about an investigation of the state of antioxidant-oxidation system for spontaneously hypertensive rats (SHR) using angiotensin-converting enzyme (ACE) drugs of short-term action. The study found that there is an increase of peroxidation processes while reducing the activity of antioxidant enzymes in the rats (SHR ), and there are features of regional influence of drugs above the level of lipid peroxidation and activity of antioxidant enzymes.
Functional state of kidneys after injection of fetal liver cells to the rats with water and salt drinking regime under the conditions of acute sublimate nephropathy
Authors: Hozhenko A. I. , Sirman V. M. , Filipets N. D. , Filipets О. О.
Published: October 2016

The experiments on non linear white rats with acute sublimate nephropathy showed that in 7 days after intraperitoneal injection of fetal liver cells (FLC ) of rats plasma creatinine concentration decreased and proximal reabsorption of sodium ions increased independently of water or salt drinking regime. The increase of natremia in rats that used tap water excluded regulatory influence of FLC on the processes of maintenance of sodium balance under the conditions of experiment. Usage of 0.9 % NaCl solution leads to increase of glomerular filtration rate, activation of tubular transport of sodium ions with predominant elevation of reabsorption in the proximal part of nephron, reduction of sodium ions loss with urination. That points to substantial role of salt drinking regimen in additional beneficial effects of FLC on renal processes in rats with acute sublimate nephropathy.
THE INFLUENCE OF HEAVY METAL S, ORGANOPHOSPHATE PESTICIDES AND PEPTIDES ON THE ENZYME ACTIVITY OF GLUTATHIONE SYSTEM
Authors: Dmukhalska Ye. B. , Honsky Ya. I.
Published: October 2016

The reduced glutathione content and the glutathione metabolism enzymes activity in organs and blood plasma of rats under conditions of lead acetate, copper sulphate and glyphosate in Roundup form were studied. The glutathioneperoxidase, the glutathionereductase activity and the concentration of glutathione decreases during action of heavy metals and glyphosate. It was found out that peptide exhibits antioxidant activity, the correction of the peptide and glutathione content.