bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbiota‐dependent metabolite trimethylamine‐N‐oxide is associated with disease severity and survival of patients with chronic heart failure
Authors: Trøseid M. , Ueland T. , Hov J. R. , Svardal A. , Gregersen I. , Dahl C. P. , Aakhus S. , Gude E. , Bjørndal B. , Halvorsen B. , Karlsen T. H. , Aukrust P. , Gullestad L. , Berge R. K. , Yndestad A.
Published: November 2014

Objectives

Recent metabolomic, experimental and clinical studies have demonstrated that trimethylamine‐N‐oxide (TMAO), a microbiota‐dependent metabolite from dietary phosphatidylcholine and carnitine, is a strong predictor of coronary artery disease (CAD). This finding suggests a link between the gut microbiota and atherosclerosis. The potential impact of TMAO in chronic heart failure (HF) is unknown. We hypothesized that TMAO levels would provide prognostic information about adverse outcomes in chronic HF.

Design

Prospective, observational study including 155 consecutive patients with chronic HF. In addition, 100 patients with stable CAD without HF and 33 matched healthy individuals were included as controls. Plasma levels of TMAO and its precursors choline and betaine were measured, and associations with symptoms, aetiology and transplant‐free survival in the patients with HF were explored.

Results

Plasma levels of TMAO (P = 0.01), choline (P < 0.001) and betaine (P < 0.001) were elevated in patients with chronic HF compared to control subjects, with the highest levels in patients with New York Heart Association (NYHA) classes III and IV. Furthermore, TMAO levels were highest in individuals with ischaemic HF, followed by those with stable CAD and nonischaemic HF. TMAO, but not choline or betaine, was associated with reduced transplant‐free survival: approximately 50% of patients in the upper tertile of TMAO levels died or received a heart transplant during 5.2 years of follow‐up (unadjusted Cox‐regression: hazard ratio 2.24, 95% confidence interval 1.28–3.92, P = 0.005).

Conclusions

TMAO levels were elevated in patients with HF and associated with NYHA class, ischaemic aetiology and adverse outcomes. Future studies should focus on gut microbiota, dietary composition and intestinal dysfunction in relation to TMAO levels and clinical outcome in HF.
Adolescent Pregnancy's Intergenerational Effects: Does an Adolescent Mother's Education Have Consequences for Her Children's Achievement?
Authors: Tang Sandra , Davis‐Kean Pamela E. , Chen Meichu , Sexton Holly R.
Published: November 2014

Although substantial work has examined the influence of adolescent pregnancy on mothers’ developmental outcomes, few studies have investigated the influence of adolescent mothers’ educational attainment on their children's achievement. This article examined the reading and math achievement trajectories of children born to adolescent and nonadolescent mothers with various levels of educational attainment. Results demonstrate that higher levels of maternal education predicted children's higher initial achievement at kindergarten and growth in achievement through eighth grade. The achievement of children with adolescent mothers, however, never reaches parity with the achievement of their peers with nonadolescent mothers. Race also predicted achievement differences. Black and Latino children of adolescent mothers were at greater risk for underachievement.
The Home and the ‘Hood: Associations Between Housing and Neighborhood Contexts and Adolescent Functioning
Authors: Elliott Margaret C. , Leventhal Tama , Shuey Elizabeth A. , Lynch Alicia Doyle , Coley Rebekah Levine
Published: November 2014

Adolescents from low‐income families face various opportunities and constraints as they develop, with possible ramifications for their well‐being. Two contexts of particular importance are the home and the neighborhood. Using adolescent data from the first two waves of the Three‐City Study (N = 1,169), this study explored associations among housing problems and neighborhood disorder with adolescents' socioemotional problems, and how these associations varied by parental monitoring and gender. Results of hierarchical linear models suggest that poor‐quality housing was most predictive of the functioning of girls and of adolescents with restrictive curfews, whereas neighborhood disorder was a stronger predictor for boys. Implications for future research on associations between housing and neighborhood contexts and adolescent development are discussed.
Insufficient vitamin D supplement use during pregnancy and early childhood: a risk factor for positional skull deformation
Authors: Weernink Marieke G.M. , van Wijk Renske M. , Groothuis‐Oudshoorn Catharina G.M. , Lanting Caren I. , Grant Cameron C. , van Vlimmeren Leo A. , Boere‐Boonekamp Magda M.
Published: November 2014

Vitamin D insufficiency during pregnancy is associated with disturbed skeletal homeostasis during infancy. Our aim was to investigate the influence of adherence to recommendations for vitamin D supplement intake of 10 μg per day (400 IU) during pregnancy (mother) and in the first months of life (child) on the occurrence of positional skull deformation of the child at the age of 2 to 4 months. In an observational case–control study, two hundred seventy‐five 2‐ to 4‐month‐old cases with positional skull deformation were compared with 548 matched controls. A questionnaire was used to gather information on background characteristics and vitamin D intake (food, time spent outdoors and supplements). In a multiple variable logistic regression analysis, insufficient vitamin D supplement intake of women during the last trimester of pregnancy [adjusted odds ratio (aOR) 1.86, 95% (CI) 1.27–2.70] and of children during early infancy (aOR 7.15, 95% CI 3.77–13.54) were independently associated with an increased risk of skull deformation during infancy. These associations were evident after adjustment for the associations with skull deformation that were present with younger maternal age and lower maternal education, shorter pregnancy duration, assisted vaginal delivery, male gender and milk formula consumption after birth. Our findings suggest that non‐adherence to recommendations for vitamin D supplement use by pregnant women and infants are associated with a higher risk of positional skull deformation in infants at 2 to 4 months of age. Our study provides an early infant life example of the importance of adequate vitamin D intake during pregnancy and infancy.
Association of maternal depression and infant nutritional status among women living with HIV in Tanzania
Authors: Kaaya Sylvia , Garcia Maria E. , Li Nan , Lienert Jeffrey , Twayigize William , Spiegelman Donna , Smith Fawzi Mary C.
Published: November 2014

Antenatal and post‐natal depression has demonstrated a significant burden in sub‐Saharan Africa, with rates ranging from 10% to 35%. However, perinatal women living with HIV in Tanzania have reported an even greater prevalence of depression (43–45%). The primary goal of this study was to examine the relationship between maternal depression and infant malnutrition among women living with HIV. The design was a retrospective cohort study within the context of a randomised controlled trial among women living with HIV and their infants. Within this trial, 699 mother–child pairs were analysed for the present study. Although antenatal depression was not associated with infant malnutrition and post‐natal depression was negatively associated [relative risk (RR = 0.80, P = 0.04], cumulative depression demonstrated a positive association with infant wasting (RR = 1.08, P < 0.01) and underweight (RR = 1.03, P < 0.01) after controlling for confounding factors. Variation in the association between depression and infant nutritional status was observed for episodic vs. chronic depression. These findings suggest that providing evidence‐based services for persistent depression among women living with HIV may have an effect on infant malnutrition. In addition, other positive outcomes may be related to infant cognitive development as well as HIV disease prognosis and survival among women.
I. AN INTRODUCTION TO THE RELATION OF PHYSICAL ACTIVITY TO COGNITIVE AND BRAIN HEALTH, AND SCHOLASTIC ACHIEVEMENT
Authors: Hillman Charles H.
Published: November 2014

The current pandemic of physical inactivity threatens both physical and cognitive health throughout the lifespan. This monograph describes the multidisciplinary study of aspects of childhood health and its relationship to cognitive and brain function, and scholastic performance. Specifically, we focus on physical activity and physical fitness along with nutrition and obesity; interconnected aspects of health that have declined over the past 30 years in children of industrialized nations. Although much emphasis has been placed on correcting physical aspects of these public health concerns, it is only more recently that attention has been paid to the relation between physical health and cognitive health among school age children. The monograph begins with an overview of current behavioral trends that compete with physical activity engagement and contribute to the failure to achieve the public health recommendations for physical activity among children in the United States. Following the epidemiological overview, the relation of childhood fitness to brain structure and function is examined among children with varying fitness levels. The observed dissimilarities between higher‐ and lower‐fit children are discussed within the context of typical brain development. To broaden the scope of research presented herein, the relation of nutrient intake—among both undernourished and well‐nourished children—and obesity on cognition and brain are discussed. Next, novel empirical data are presented from a correlational study that indicates a differential relation between childhood fitness and adiposity on various aspects of cognition. In an effort to provide a more comprehensive review, a later chapter is dedicated to describing a small body of literature investigating the relation of physical activity to special populations of children, including those with learning disorders. In doing so, practical applications as well as challenges and limitations of implementing physical activity into the lives of children with learning disabilities are described. Finally, a detailed review and historical analysis of the relation of physical activity to scholastic performance is provided. This translational chapter provides an important application of the laboratory findings to a real world setting in which children rely upon attention, memory, and learning for scholastic success. Accordingly, this monograph is directed toward timely and important public health issues related to chronic disease prevention as a function of childhood inactivity and obesity with the goal of linking health behaviors to cognitive and brain health, and scholastic performance.
Complications related to early mobilization of mechanically ventilated patients on Intensive Care Units
Authors: Nydahl Peter , Ewers Andre , Brodda Diana
Published: November 2014

Aims and objectives

To compare international literature on the detection of complications associated with early mobilization of mechanically ventilated patients in intensive care units (ICUs).

Background

Early mobilization of mechanically ventilatedICUpatients is considered to be a more beneficial approach to treatment in intensive care; however, it remains unclear how safe this approach is and what complications to expect.

Search strategies

A systematic literature research in English and German was conducted in June 2013 in the databases Pubmed,CINAHL, Cochrane library andMedPilotwithout limiting by year of publication. References of the included studies were screened and supplemented by manual search.

Inclusion and exclusion criteria

Inclusion criteria were studies about mechanically ventilated adult patients onICU, who were mobilized and reported complications. Excluded were studies that (a) did not differentiate between non‐ventilated and ventilated patients, (b) did not report complications and (c) focused on in‐bed mobilization.

Conclusions

Of 952 titles, 16 articles fit the criteria including 3 reviews and 13 clinical trials. The percentage of complications in clinical trials ranged between 0% and 16%. In total, 453 patients were mobilized 3613 times (up to walking with ventilation) with a complication mean rate of 3·9% (n= 144) using the inherent safety limits. No fall, cardiac arrest, or death was reported. Most complications were pulmonary, followed by haemodynamic ones. Serious complications that led to further consequences were observed in 0·3% (n= 10) of all mobilizations. The clinical studies have been carried out in trained, interdisciplinary teams with most of them using adapted algorithms for safety.

Relevance to clinical practice

Despite a low complication rate, a frame for safety during early mobilization including team training and adapted criteria is recommended.
A simplified emergency trauma score for predicting mortality in emergency setting
Authors: Yuen Margaret SY , Mann Stephen KF , Chow Daniel HK
Published: November 2014

Aims

The aim of the study was to develop a simplified emergency trauma score (SETS) for rating injury severity as well as triaging and predicting mortality in Hong Kong.

Background

Many existing trauma scoring systems require measurements that are not generally available in emergency settings in Hong Kong. As many of these important measures in the scoring systems are not available before the patients are admitted in the hospitals, it may delay treatment because of the extent of a patient's injury is often not clear at the site of accident or in the emergency settings.

Design

A retrospective cohort analysis of trauma patients' records from Trauma Registry in Hong Kong was performed.

Method

Potential significant parameters in predicting mortality were identified by univariate analysis. Binary logistic regression then was used to develop an equation forSETS. Four parameters including age, Glasgow coma scale, respiratory rate and American College of Surgeons (ACS) mechanism of injury were identified, and the reliability and validity ofSETSwas assessed.

Results

At cut‐off point of aSETSscore of 60, the sensitivity and specificity ofSETSwere 64% and 98% respectively. The area under receiver operating characteristic curve was 0·939 which was comparable with other commonly used trauma scores.

Conclusions

SETSshould be considered a relevant trauma scoring system in Hong Kong emergency settings. It is suggested that similar scoring systems should be developed in other countries based upon obtainable measures in their corresponding emergency settings.

Relevance to clinical practice

As a trauma scoring system is closely related to the context of its application, a system that can facilitate accurate sorting of patients into treatment hierarchies should be adopted in the congested emergency settings.
Evolving trends in nurse regulation: what are the policy impacts for nursing's social mandate?
Authors: Duncan Susan , Thorne Sally , Rodney Patricia
Published: November 2014

We recognize a paradox of power and promise in the context of legislative and organizational changes in nurse regulation which poses constraints on nursing's capacity to bring voice and influence to pressing matters of healthcare and public policy. The profession is at an important crossroads wherein leaders must be well informed in political, economic and legislative trends to harness the profession's power while also navigating forces that may put at risk its central mission to serve society. We present a critical policy analysis of the impact of recent regulatory trends on what the International Council of Nurses considers nursing's three ‘pillars’ – the profession of nursing, socioeconomic welfare of nurses and nurse regulation. Themes surfacing from this analysis include regulatory discontinuity, a tightening of regulatory control, and an increasingly managerial governance culture. These themes illuminate insights and strategies required to renew and revitalize the social mandate of our profession amidst a climate of urgency in the questioning of nurse scholars with respect to the future of the profession. At this historic juncture, nurses must clearly understand the implications of legislative and organizational regulatory changes to ensure the profession contributes to full capacity in achieving health and health equity globally.
RNA‐Seq bulked segregant analysis enables the identification of high‐resolution genetic markers for breeding in hexaploid wheat
Authors: Ramirez‐Gonzalez Ricardo H. , Segovia Vanesa , Bird Nicholas , Fenwick Paul , Holdgate Sarah , Berry Simon , Jack Peter , Caccamo Mario , Uauy Cristobal
Published: November 2014

The identification of genetic markers linked to genes of agronomic importance is a major aim of crop research and breeding programmes. Here, we identify markers for Yr15, a major disease resistance gene for wheat yellow rust, using a segregating F2 population. After phenotyping, we implemented RNA sequencing (RNA‐Seq) of bulked pools to identify single‐nucleotide polymorphisms (SNP) associated with Yr15. Over 27 000 genes with SNPs were identified between the parents, and then classified based on the results from the sequenced bulks. We calculated the bulk frequency ratio (BFR) of SNPs between resistant and susceptible bulks, selecting those showing sixfold enrichment/depletion in the corresponding bulks (BFR > 6). Using additional filtering criteria, we reduced the number of genes with a putative SNP to 175. The 35 SNPs with the highest BFR values were converted into genome‐specific KASP assays using an automated bioinformatics pipeline (PolyMarker) which circumvents the limitations associated with the polyploid wheat genome. Twenty‐eight assays were polymorphic of which 22 (63%) mapped in the same linkage group as Yr15. Using these markers, we mapped Yr15 to a 0.77‐cM interval. The three most closely linked SNPs were tested across varieties and breeding lines representing UK elite germplasm. Two flanking markers were diagnostic in over 99% of lines tested, thus providing a reliable haplotype for marker‐assisted selection in these breeding programmes. Our results demonstrate that the proposed methodology can be applied in polyploid F2 populations to generate high‐resolution genetic maps across target intervals.
Potential of a tomato MAGIC population to decipher the genetic control of quantitative traits and detect causal variants in the resequencing era
Authors: Pascual Laura , Desplat Nelly , Huang Bevan E. , Desgroux Aurore , Bruguier Laure , Bouchet Jean‐Paul , Le Quang H. , Chauchard Betty , Verschave Philippe , Causse Mathilde
Published: November 2014

Identification of the polymorphisms controlling quantitative traits remains a challenge for plant geneticists. Multiparent advanced generation intercross (MAGIC) populations offer an alternative to traditional linkage or association mapping populations by increasing the precision of quantitative trait loci (QTL) mapping. Here, we present the first tomato MAGIC population and highlight its potential for the valorization of intraspecific variation, QTL mapping and causal polymorphism identification. The population was developed by crossing eight founder lines, selected to include a wide range of genetic diversity, whose genomes have been previously resequenced. We selected 1536 SNPs among the 4 million available to enhance haplotype prediction and recombination detection in the population. The linkage map obtained showed an 87% increase in recombination frequencies compared to biparental populations. The prediction of the haplotype origin was possible for 89% of the MAGIC line genomes, allowing QTL detection at the haplotype level. We grew the population in two greenhouse trials and detected QTLs for fruit weight. We mapped three stable QTLs and six specific of a location. Finally, we showed the potential of the MAGIC population when coupled with whole genome sequencing of founder lines to detect candidate SNPs underlying the QTLs. For a previously cloned QTL on chromosome 3, we used the predicted allelic effect of each founder and their genome sequences to select putative causal polymorphisms in the supporting interval. The number of candidate polymorphisms was reduced from 12 284 (in 800 genes) to 96 (in 54 genes), including the actual causal polymorphism. This population represents a new permanent resource for the tomato genetics community.
Sub‐lethal UV‐C radiation induces callose, hydrogen peroxide and defence‐related gene expression in Arabidopsis thaliana
Authors: Mintoff S. J. L. , Rookes J. E. , Cahill D. M.
Published: November 2014

Exposure of plants to UV‐C irradiation induces gene expression and cellular responses that are commonly associated with wounding and pathogen defence, and in some cases can lead to increased resistance against pathogen infection. We examined, at a physiological, molecular and biochemical level, the effects of and responses to, sub‐lethal UV‐C exposure on Arabidopsis plants when irradiated with increasing dosages of UV‐C radiation. Following UV‐C exposure plants had reduced leaf areas over time, with the severity of reduction increasing with dosage. Severe morphological changes that included leaf glazing, bronzing and curling were found to occur in plants treated with the 1000 J·m−2 dosage. Extensive damage to the mesophyll was observed, and cell death occurred in both a dosage‐ and time‐dependent manner. Analysis of H2O2 activity and the pathogen defence marker genes PR1 and PDF1.2 demonstrated induction of these defence‐related responses at each UV‐C dosage tested. Interestingly, in response to UV‐C irradiation the production of callose (β‐1,3‐glucan) was identified at all dosages examined. Together, these results show plant responses to UV‐C irradiation at much lower doses than have previously been reported, and that there is potential for the use of UV‐C as an inducer of plant defence.
Negative and positive interactions among plants: effects of competitors and litter on seedling emergence and growth of forest and grassland species
Authors: Loydi A. , Donath T. W. , Otte A. , Eckstein R. L.
Published: November 2014

Living plant neighbours, but also their dead aboveground remains (i.e. litter), may individually exert negative or positive effects on plant recruitment. Although living plants and litter co‐occur in most ecosystems, few studies have addressed their combined effects, and conclusions are ambivalent. Therefore, we examined the response in terms of seedling emergence and growth of herbaceous grassland and forest species to different litter types and amounts and the presence of competitors. We conducted a pot experiment testing the effects of litter type (grass, oak), litter amount (low, medium, high) and interspecific competition (presence or absence of four Festuca arundinacea individuals) on seedling emergence and biomass of four congeneric pairs of hemicryptophytes from two habitat types (woodland, grassland). Interactions between litter and competition were weak. Litter presence increased competitor biomass. It also had positive effects on seedling emergence at low litter amounts and negative effects at high litter amounts, while competition had no effect on seedling emergence. Seedling biomass was negatively affected by the presence of competitors, and this effect was stronger in combination with high amounts of litter. Litter affected seedling emergence while competition determined the biomass of the emerged individuals, both affecting early stages of seedling recruitment. High litter accumulation also reduced seedling biomass, but this effect seemed to be additive to competitor effects. This suggests that live and dead plant mass can affect species recruitment in natural systems, but the mechanisms by which they operate and their timing differ.
Facilitating particularization of repeated similar events with context‐specific cues
Authors: Willén Rebecca M. , Granhag Pär Anders , Strömwall Leif A. , Fisher Ronald P.
Published: November 2014

Ninety‐five dental care patients participated in a quasi‐experiment in which they were interviewed twice about dental visits they had made during the past ten years. Objective truth was established by analysing their dental records. The main purpose of the study was to investigate to what extent context‐specific cues could facilitate particularization (i.e., recollection of events and details) of repeated and similar events. A mixed design was employed and the effects of three types of cues were explored: two types of context‐specific cues vs. cues commonly used in police practise when interviewing plaintiffs. In line with our hypothesis, context‐specific cues tended to be more effective for recollection of individual events than the comparison cues. In addition, context‐specific cues generated more details than the comparison cues and the difference was marginally significant. Rehearsal of the memories by telling them to others was associated with an increased number of recollected events and details. The results are discussed from a legal psychology perspective with focus on recollection of repeated abuse.
Assessing the Adherence to Guidelines of Media Reporting of Suicide Using a Novel Instrument—the “Risk of Imitative Suicide Scale” (RISc)
Authors: Nutt Rachel , Kidd Brian , Matthews Keith
Published: November 2014

Media guidelines for reporting of suicide are considered important in suicide prevention because of the risk of “imitative” suicide. There are currently no established tools for the quantification of quality of reporting. We sought to develop and validate a quality assessment instrument—the Risk of Imitative Suicide Scale (RISc). The RISc appears capable of discriminating reliably between adherent and nonadherent articles. Our data suggest that adherence to guidelines is inconsistent, and there are major differences between web‐based and print media. The RISc could be used to evaluate effectiveness and consistency of media engagement with suicide prevention strategies.
The Opinions of GP's Patients About Suicide, Assisted Suicide, Euthanasia, and Suicide Prevention: An Italian Survey
Authors: Poma Stefano Zanone , Vicentini Silvia , Siviero Francesca , Grossi Antonello , Toniolo Emanuele , Baldo Vincenzo , Leo Diego De
Published: November 2014

A survey about opinions on end‐of‐life issues of a population represented by 1,171 people in the waiting room of general practitioners' surgeries was conducted in a province of northern Italy. Most subjects did not consider suicide as a reasonable option even in cases of a serious and incurable disease. Moreover, subjects did not consider euthanasia as a possible option either; however, they did express an opposite attitude when considering euthanasia in a third‐person perspective. People with a personal history of suicidal behavior appear to present as a different population, overall expressing more open attitudes.
Osteopetrosis in obese female rats is site‐specifically inhibited by physical training
Authors: Lacerda Débora Romualdo , Serakides Rogéria , de Melo Ocarino Natalia , Ferreira Adaliene Versiani Matos , Moraes Michele Macedo , Boeloni Jankerle Neves , Silva Juneo Freitas , de Oliveira Marina Chaves , de Barcellos Luiz Alexandre Medrado , Rodrigues Luiz Oswaldo Carneiro , Soares Danusa Dias
Published: November 2014

New Findings

What is the central question of this study?

Clinical studies suggest that obesity ‘protects’ against osteoporosis. However, these studies used only bone densitometry and assessed only one bone site, which is insufficient to enable conclusions to be drawn about the response of the whole skeleton. Furthermore, the effects of exercise on bone responses in obesity have not been explored previously.

What is the main finding and what is its importance?

We show that obesity causes osteopetrosis. Therefore, the classical perspective of ‘protective effects of obesity’ needs to be reviewed, and exercise is an important tool to avoid these alterations and to maintain the homeostasis of bone.

A sedentary lifestyle and obesity induce systemic inflammatory responses. Although the effects of physical inactivity on osseous tissue have been well established, the effects of obesity on bone tissue remain controversial. Furthermore, the effects of physical training on bone tissue responses in the presence of diet‐induced obesity are unknown. Our aim was to investigate the effects of obesity and physical training at multiple bone sites in rats. Female Wistar rats were divided into the following four groups: (i) control diet, non‐trained (C‐NT); (ii) high‐refined carbohydrate‐containing diet, non‐trained (HC‐NT); (iii) control diet, trained (C‐T); and (iv) high‐refined carbohydrate‐containing diet, trained (HC‐T). At 5 months of age, the rats were submitted to daily exercise for 30 min day−1. After 13 weeks, blood samples, adipose and skeletal tissues were harvested. Two‐way ANOVA was applied to detect differences (significance accepted when P ≤ 0.05). The HC‐NT group exhibited increased body mass, adiposity, serum leptin, serum insulin, insulin resistance index and concentrations of tumour necrosis factor‐α and interleukin‐6. Obese rats (HC‐NT) exhibited thickening of nasal bones, trabecular bones in the lumbar vertebrae and long bones in a site‐dependent manner. The HC‐T group exhibited similar adiposity and inflammatory results. Morphological analysis of the lumbar vertebrae in rats fed the HC diet revealed characteristics of osteopetrosis that were inhibited by exercise. In conclusion, the HC diet induced obesity and inflammatory/hormonal alterations and increased the trabecular bone in a site‐dependent manner. However, obesity caused osteopetrosis in the lumbar vertebrae, which could be inhibited by physical training. Although exercise inhibited the development of bone alterations, physical training did not inhibit the HC diet‐induced obesity responses.
Vagus nerve stimulation reverses ventricular electrophysiological changes induced by hypersympathetic nerve activity
Authors: Huang Jie , Qian Jin , Yao Wei , Wang Neng , Zhang Zhenjian , Cao Chuanbin , Song Bo , Zhang Zhuo
Published: November 2014

New Findings

What is the central question of this study?

Previous studies have shown that hypersympathetic nerve activity results in ventricular electrophysiological changes and facilitates the occurrence of ventricular arrhythmias. Vagus nerve stimulation has shown therapeutic potential for myocardial infarction‐induced ventricular arrhythmias. However, the actions of vagus nerve stimulation on hypersympathetic nerve activity‐induced ventricular electrophysiological changes are still unknown.

What is the main finding and its importance?

We show that vagus nerve stimulation is able to reverse hypersympathetic nerve activity‐induced ventricular electrophysiological changes and suppress the occurrence of ventricular fibrillation. These findings further suggest that vagus nerve stimulation may be an effective treatment option for ventricular arrhythmias, especially in patients with myocardial infarction or heart failure.

Vagus nerve stimulation (VNS) has shown therapeutic potential for myocardial infarction‐induced ventricular arrhythmias. This study aimed to investigate the effects of VNS on ventricular electrophysiological changes induced by hypersympathetic nerve activity. Seventeen open‐chest dogs were subjected to left stellate ganglion stimulation (LSGS) for 4 h to simulate hypersympathetic tone. All animals were randomly assigned to the VNS group (n = 9) or the control group (n = 8). In the VNS group, VNS was performed at the voltage causing a 10% decrease in heart rate for hours 3–4 during 4 h of LSGS. During the first 2 h of LSGS, the ventricular effective refractory period (ERP) and action potential duration (APD) were both progressively and significantly decreased; the spatial dispersion of ERP, maximal slope of the restitution curve and pacing cycle length of APD alternans were all increased. With LSGS + VNS during the next 2 h, there was a significant return of all the altered electrophysiological parameters towards baseline levels. In the eight control dogs that received 4 h of LSGS without VNS, all the parameters changed progressively, but without any reversals. The ventricular fibrillation threshold was higher in the VNS group than in the control group (17.3 ± 3.4 versus 11.3 ± 3.8 V, P < 0.05). The present study demonstrated that VNS was able to reverse LSGS‐induced ventricular electrophysiological changes and suppress the occurrence of ventricular fibrillation.
Microtubule stabilization with paclitaxel does not protect against infarction in isolated rat hearts
Authors: Rodríguez‐Sinovas Antonio , Abad Elena , Sánchez Jose A. , Fernández‐Sanz Celia , Inserte Javier , Ruiz‐Meana Marisol , Alburquerque‐Béjar Juan José , García‐Dorado David
Published: November 2014

New Findings

What is the central question of this study?

The microtubule network is disrupted during myocardial ischaemia–reperfusion injury. It was suggested that prevention of microtubule disruption with paclitaxel might reduce cardiac infarct size; however, the effects on infarction have not been studied.

What is the main finding and its importance?

Paclitaxel caused a reduction in microtubule disruption and cardiomyocyte hypercontracture during ischaemia–reperfusion. However, it induced a greater increase in cytosolic calcium, which may explain the lack of effect against infarction that we have seen in isolated rat hearts. The large increase in perfusion pressure induced by paclitaxel in this model may have clinical implications, because detrimental effects of the drug were reported after its clinical application.

Microtubules play a major role in the transmission of mechanical forces within the myocardium and in maintenance of organelle function. However, this intracellular network is disrupted during myocardial ischaemia–reperfusion. We assessed the effects of prevention of microtubule disruption with paclitaxel on ischaemia–reperfusion injury in isolated rat cardiomyocytes and hearts. Isolated rat cardiomyocytes were submitted to normoxia (1 h) or 45 min of simulated ischaemia (pH 6.4, 0% O2, 37°C) and reoxygenation, without or with treatment with the microtubule stabilizer, paclitaxel (10−5 m), or the inhibitor of microtubule polymerization, colchicine (5 × 10−6 m). Simulated ischaemia leads to microtubule disruption before the onset of ischaemic contracture. Paclitaxel attenuated both microtubule disruption and the incidence of hypercontracture, whereas treatment with colchicine mimicked the effects of simulated ischaemia and reoxygenation. In isolated normoxic rat hearts, treatment with paclitaxel induced concentration‐dependent decreases in heart rate and left ventricular developed pressure and increases in perfusion pressure. Despite protection against hypercontracture, paclitaxel pretreatment did not modify infarct size (60.37 ± 2.27% in control hearts versus 58.75 ± 10.25, 55.44 ± 10.32 and 50.06 ± 10.14% after treatment with 10−6, 3 × 10−6 and 10−5 m of paclitaxel) after 60 min of global ischaemia and reperfusion in isolated rat hearts. Lack of protection was correlated with a higher increase in cytosolic calcium levels during simulated ischaemia in cardiomyocytes treated with paclitaxel (2.32 ± 0.15 versus 1.13 ± 0.16 a.u. in the presence or absence of 10−6 m paclitaxel, respectively, P < 0.05), but not with changes in aortic reactivity. In conclusion, microtubule stabilization with paclitaxel reduces hypercontracture in isolated rat cardiomyocytes but does not protect against infarction in isolated rat hearts.
Recruitment of Gβγ controls the basal activity of G‐protein coupled inwardly rectifying potassium (GIRK) channels: crucial role of distal C terminus of GIRK1
Authors: Kahanovitch Uri , Tsemakhovich Vladimir , Berlin Shai , Rubinstein Moran , Styr Boaz , Castel Ruth , Peleg Sagit , Tabak Galit , Dessauer Carmen W. , Ivanina Tatiana , Dascal Nathan
Published: November 2014

Key points

The G‐protein coupled inwardly rectifying potassium (GIRK) channel is an important mediator of neurotransmission via Gβγ subunit of the heterotrimeric Gi/o protein released by G‐protein coupled receptor (GPCR) activation.

Channels containing the GIRK1 subunit exhibit high basal currents, whereas channels that are formed by the GIRK2 subunit have very low basal currents.

GIRK1‐containing channels, but not channels consisting of GIRK2 only, recruit Gβγ to the plasma membrane. The Gα subunit of the G protein is not recruited by either GIRK1/2 or GIRK2.

The unique distal C terminus of GIRK1 (G1‐dCT) endows the channel with strong interaction with Gβγ, and deletion of G1‐dCT abolishes the Gβγ recruitment and reduces the basal currents.

These findings suggest that the basal activity of GIRK channels depends on channel‐induced recruitment of Gβγ. The unique C terminus of GIRK1 subunit plays an important role in Gβγ recruitment.

The G‐protein coupled inwardly rectifying potassium (GIRK, or Kir3) channels are important mediators of inhibitory neurotransmission via activation of G‐protein coupled receptors (GPCRs). GIRK channels are tetramers comprising combinations of subunits (GIRK1–4), activated by direct binding of the Gβγ subunit of Gi/o proteins. Heterologously expressed GIRK1/2 exhibit high, Gβγ‐dependent basal currents (Ibasal) and a modest activation by GPCR or coexpressed Gβγ. Inversely, the GIRK2 homotetramers exhibit low Ibasal and strong activation by Gβγ. The high Ibasal of GIRK1 seems to be associated with its unique distal C terminus (G1‐dCT), which is not present in the other subunits. We investigated the role of G1‐dCT using electrophysiological and fluorescence assays in Xenopus laevis oocytes and protein interaction assays. We show that expression of GIRK1/2 increases the plasma membrane level of coexpressed Gβγ (a phenomenon we term ‘Gβγ recruitment’) but not of coexpressed Gαi3. All GIRK1‐containing channels, but not GIRK2 homomers, recruited Gβγ to the plasma membrane. In biochemical assays, truncation of G1‐dCT reduces the binding between the cytosolic parts of GIRK1 and Gβγ, but not Gαi3. Nevertheless, the truncation of G1‐dCT does not impair activation by Gβγ. In fluorescently labelled homotetrameric GIRK1 channels and in the heterotetrameric GIRK1/2 channel, the truncation of G1‐dCT abolishes Gβγ recruitment and decreases Ibasal. Thus, we conclude that G1‐dCT carries an essential role in Gβγ recruitment by GIRK1 and, consequently, in determining its high basal activity. Our results indicate that G1‐dCT is a crucial part of a Gβγ anchoring site of GIRK1‐containing channels, spatially and functionally distinct from the site of channel activation by Gβγ.
Plasmid-Mediated Resistance to Cephalosporins and Fluoroquinolones in Various Escherichia coli Sequence Types Isolated from Rooks Wintering in Europe
Authors: Jamborova Ivana , Dolejska Monika , Vojtech Jiri , Guenther Sebastian , Uricariu Raluca , Drozdowska Joanna , Papousek Ivo , Pasekova Katerina , Meissner Wlodzimierz , Hordowski Jozef , Cizek Alois , Literak Ivan
Published: November 2014

Extended-spectrum-beta-lactamase (ESBL)-producing, AmpC beta-lactamase-producing, and plasmid-mediated quinolone resistance (PMQR) gene-positive strains of
Escherichia coli
were investigated in wintering rooks (
Corvus frugilegus
) from eight European countries. Fecal samples (
n
= 1,073) from rooks wintering in the Czech Republic, France, Germany, Italy, Poland, Serbia, Spain, and Switzerland were examined. Resistant isolates obtained from selective cultivation were screened for ESBL, AmpC, and PMQR genes by PCR and sequencing. Pulsed-field gel electrophoresis and multilocus sequence typing were performed to reveal their clonal relatedness. In total, from the 1,073 samples, 152 (14%) cefotaxime-resistant
E. coli
isolates and 355 (33%)
E. coli
isolates with reduced susceptibility to ciprofloxacin were found. Eighty-two (54%) of these cefotaxime-resistant
E. coli
isolates carried the following ESBL genes:
bla
CTX-M-1
(
n
= 39 isolates),
bla
CTX-M-15
(
n
= 25),
bla
CTX-M-24
(
n
= 4),
bla
TEM-52
(
n
= 4),
bla
CTX-M-14
(
n
= 2),
bla
CTX-M-55
(
n
= 2),
bla
SHV-12
(
n
= 2),
bla
CTX-M-8
(
n
= 1),
bla
CTX-M-25
(
n
= 1),
bla
CTX-M-28
(
n
= 1), and an unspecified gene (
n
= 1). Forty-seven (31%) cefotaxime-resistant
E. coli
isolates carried the
bla
CMY-2
AmpC beta-lactamase gene. Sixty-two (17%) of the
E. coli
isolates with reduced susceptibility to ciprofloxacin were positive for the PMQR genes
qnrS1
(
n
= 54),
qnrB19
(
n
= 4),
qnrS1
and
qnrB19
(
n
= 2),
qnrS2
(
n
= 1), and
aac(6′)-Ib-cr
(
n
= 1). Eleven isolates from the Czech Republic (
n
= 8) and Serbia (
n
= 3) were identified to be CTX-M-15-producing
E. coli
clone B2-O25b-ST131 isolates. Ninety-one different sequence types (STs) among 191 ESBL-producing, AmpC-producing, and PMQR gene-positive
E. coli
isolates were determined, with ST58 (
n
= 15), ST10 (
n
= 14), and ST131 (
n
= 12) predominating. The widespread occurrence of highly diverse ESBL- and AmpC-producing and PMQR gene-positive
E. coli
isolates, including the clinically important multiresistant ST69, ST95, ST117, ST131, and ST405 clones, was demonstrated in rooks wintering in various European countries.
Modeling the Recovery of Heat-Treated Bacillus licheniformis Ad978 and Bacillus weihenstephanensis KBAB4 Spores at Suboptimal Temperature and pH Using Growth Limits
Authors: Trunet C. , Mtimet N. , Mathot A.-G. , Postollec F. , Leguerinel I. , Sohier D. , Couvert O. , Carlin F. , Coroller L.
Published: November 2014

The apparent heat resistance of spores of
Bacillus weihenstephanensis
and
Bacillus licheniformis
was measured and expressed as the time to first decimal reduction (δ value) at a given recovery temperature and pH. Spores of
B. weihenstephanensis
were produced at 30°C and 12°C, and spores of
B. licheniformis
were produced at 45°C and 20°C.
B. weihenstephanensis
spores were then heat treated at 85°C, 90°C, and 95°C, and
B. licheniformis
spores were heat treated at 95°C, 100°C, and 105°C. Heat-treated spores were grown on nutrient agar at a range of temperatures (4°C to 40°C for
B. weihenstephanensis
and 15°C to 60°C for
B. licheniformis
) or a range of pHs (between pH 4.5 and pH 9.5 for both strains). The recovery temperature had a slight effect on the apparent heat resistance, except very near recovery boundaries. In contrast, a decrease in the recovery pH had a progressive impact on apparent heat resistance. A model describing the heat resistance and the ability to recover according to the sporulation temperature, temperature of treatment, and recovery temperature and pH was proposed. This model derived from secondary mathematical models for growth prediction. Previously published cardinal temperature and pH values were used as input parameters. The fitting of the model with apparent heat resistance data obtained for a wide range of spore treatment and recovery conditions was highly satisfactory.
Pyrosequencing of
mcrA
and Archaeal 16S rRNA Genes Reveals Diversity and Substrate Preferences of Methanogen Communities in Anaerobic Digesters
Authors: Wilkins David , Lu Xiao-Ying , Shen Zhiyong , Chen Jiapeng , Lee Patrick K. H.
Published: November 2014

Methanogenic archaea play a key role in biogas-producing anaerobic digestion and yet remain poorly taxonomically characterized. This is in part due to the limitations of low-throughput Sanger sequencing of a single (16S rRNA) gene, which in the past may have undersampled methanogen diversity. In this study, archaeal communities from three sludge digesters in Hong Kong and one wastewater digester in China were examined using high-throughput pyrosequencing of the methyl coenzyme M reductase (
mcrA
) and 16S rRNA genes.
Methanobacteriales
,
Methanomicrobiales
, and
Methanosarcinales
were detected in each digester, indicating that both hydrogenotrophic and acetoclastic methanogenesis was occurring. Two sludge digesters had similar community structures, likely due to their similar design and feedstock. Taxonomic classification of the
mcrA
genes suggested that these digesters were dominated by acetoclastic methanogens, particularly
Methanosarcinales
, while the other digesters were dominated by hydrogenotrophic
Methanomicrobiales
. The proposed euryarchaeotal order
Methanomassiliicoccales
and the uncultured WSA2 group were detected with the 16S rRNA gene, and potential
mcrA
genes for these groups were identified. 16S rRNA gene sequencing also recovered several crenarchaeotal groups potentially involved in the initial anaerobic digestion processes. Overall, the two genes produced different taxonomic profiles for the digesters, while greater methanogen richness was detected using the
mcrA
gene, supporting the use of this functional gene as a complement to the 16S rRNA gene to better assess methanogen diversity. A significant positive correlation was detected between methane production and the abundance of
mcrA
transcripts in digesters treating sludge and wastewater samples, supporting the
mcrA
gene as a biomarker for methane yield.
Synthesis and Succinylation of Subtilin-Like Lantibiotics Are Strongly Influenced by Glucose and Transition State Regulator AbrB
Authors: Bochmann Sophie M. , Spieß Tobias , Kötter Peter , Entian Karl-Dieter
Published: November 2014

Subtilin and the closely related entianin are class I lantibiotics produced by different subspecies of
Bacillus subtilis
. Both molecules are ribosomally synthesized peptide antibiotics with unusual ring structures. Subtilin-like lantibiotics develop strong antibiotic activities against various Gram-positive organisms with an efficiency similar to that of nisin from
Lactococcus lactis
. In contrast to nisin, subtilin-like lantibiotics partially undergo an additional posttranslational modification, where the N-terminal tryptophan residue becomes succinylated, resulting in drastically reduced antibiotic activities. A highly sensitive high-performance liquid chromatography (HPLC)-based quantification method enabled us to determine entianin and succinylated entianin (S-entianin) concentrations in the supernatant during growth. We show that entianin synthesis and the degree of succinylation drastically change with culture conditions. In particular, increasing glucose concentrations resulted in higher entianin amounts and lower proportions of S-entianin in Landy-based media. In contrast, no succinylation was observed in medium A with 10% glucose. Interestingly, glucose retarded the expression of entianin biosynthesis genes. Furthermore, deletion of the transition state regulator AbrB resulted in a 6-fold increased entianin production in medium A with 10% glucose. This shows that entianin biosynthesis in
B. subtilis
is strongly influenced by glucose, in addition to its regulation by the transition state regulator AbrB. Our results suggest that the mechanism underlying the succinylation of subtilin-like lantibiotics is enzymatically catalyzed and occurs in the extracellular space or at the cellular membrane.