bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventilatory response during an incremental exercise test: A mode of testing effect
Authors: Power Geoffrey A. , Handrigan Grant A. , Basset Fabien A.
Published: November 2011

This study compared ventilation patterns during incremental load tests to exhaustion. Ten endurance trained individuals and eight recreationally active trained individuals underwent a maximal oxygen uptake (O2max) determination test on both a cycle (CE) and treadmill (TM) ergometer. Cardiorespiratory variables O2,CO2, RER, E, and R), movement frequency (MF) and entrainment (ENT) were collected and calculated relative to fixed percentages of O2max (isometabolic), ranging from 60 to 100%. Minute ventilation ( E) was similar between groups on both ergometers. Concurrently, VT was significantly higher, while R was significantly lower on the CE compared to the TM in both groups (P<0.05). At isometabolic intensities there were no difference in R or ENT between groups or mode of testing while the endurance trained group reached higher VT values on the CE. Although the endurance trained group reached higher cardiorespiratory values compared to the recreationally active trained group, their ventilatory patterns were similar between modes of testing. These results seem to be dependent on the exercise modality and not necessarily the type of training individuals regularly participate in.
Supervised slackline training improves postural stability
Authors: Pfusterschmied Jürgen , Buchecker Michael , Keller Martin , Wagner Herbert , Taube Wolfgang , Müller Erich
Published: November 2011

The present study investigated whether or not four weeks of supervised slackline training (SLT) performed on nylon webbing improves postural stability. Twenty‐four healthy adults participated in the study and were assigned to either SLT (n=12) or a control (CON) group (n=12). The SLT group completed a four week training program, while the CON group received no training. Centre of gravity (COG) and joint angles (ankle, knee and hip) were calculated using whole body three‐dimensional (3D) kinematic measurements during single leg standing on a stable surface (SS) and on a perturbed surface (PS) before and after training. After SLT, a significant interaction was found for the SS condition in anterior‐posterior COG mean velocity, whereas no changes were observed in the medio‐lateral direction or in joint kinematics. In the PS condition, the medio‐lateral COG mean velocity, frontal angular range of motion in the knee and hip joint, sagittal angular mean velocity in the knee joint, as well as frontal angular mean velocity in the hip joint were reduced in the SLT group only (all P<0.05). No significant training effects were detected in the ankle joint kinematics in either group from pre to post test. Our findings demonstrate that four weeks of supervised SLT improves postural stability in single leg stance on a stable surface and/or during compensation of perturbations.
Pre‐cooling for football training and competition in hot and humid conditions
Authors: Duffield Rob , Coutts Aaron , McCall Alan , Burgess Darren
Published: November 2011

Pre‐cooling studies report positive physiological and performance benefits in laboratory conditions, although research studies have not investigated these reported benefits in ecologically valid team‐sport training and competition settings. Accordingly, this study investigated the effect of field‐based pre‐cooling strategies for professional football players during training and competition in the heat. Ten professional football players from an Australian A‐League club performed two training sessions and competitive matches in hot ambient conditions (29±3oC, 78±8% relative humidity) with or without pre‐cooling. The pre‐cooling intervention involved 20‐min of an ice‐vest, cold towels and 350 mL ice‐slushie drink. Training sessions (n=9) were randomised, and consisted of 2 × 10‐min interval training, followed by 6 × 3‐min of 5v5 small sided games. Competitions (n=7) involved official A‐League matches during the 2009–10 season. Player movement characteristics, core temperature (gastrointestinal), skin temperature, nude mass, heart rate, capillary blood (glucose, K+, Na+, haematocrit), perceptual exertion and thermal stress measures were recorded. No significant differences (P>0.05) were present between conditions for any measure of physical performance, although moderate‐large effects for a greater total and relative distance covered during training were present (d > 0.8). While mean skin temperature was reduced following cooling, core temperature was only lower until following the warm‐up in training and was even less evident during matches (P>0.05; d < 0.6). However, a smaller change in mass (sweat loss) and reduced perceptual exertion and thermal stress were evident during training following cooling (d > 0.9), although again, to a much lesser extent in matches (d = 0.6). In conclusion, equivocal findings were present for the effects of pre‐cooling for professional football players during competitive training and matches in the heat. However, performance and thermoregulatory response trends showed similarities to previous laboratory evidence. The field‐based nature of the current study may highlight that the transfer of lab findings to field settings is difficult or the strength of the intervention is diminished by the settings.
The influence of relative age on the composition of professional soccer squads
Authors: Ostapczuk Martin , Musch Jochen
Published: November 2011

Children born shortly after the cut‐off date applying for age grouping in minor sports profit from being able to remain for almost an additional year in their respective age group compared to those born later in the same year. A shift of the cut‐off date in German youth soccer in 1997 allowed us to investigate the effect of a favourable relative age as well as the effect of a change of the cut‐off date on the birth‐date distribution of soccer players in the Bundesliga (Division 1), the highest professional soccer league in Germany. Both the cut‐off date and the change of the cut‐off date exerted a significant influence on the composition of professional senior squads. In the 1997/98 season, there was an overrepresentation of players profiting from the old cut‐off date of 1 August. In the 2007/08 season, 10 years after the change of the cut‐off date, there was an overrepresentation of players born shortly after the new cut‐off date of 1 January. This pattern of results shows that owing to the cut‐off dates applying in youth soccer, the date of birth of young players systematically influences their later professional success and career.
Technical performance effectiveness subsequent to complex motor skills training in young boxers
Authors: El Ashker Said
Published: November 2011

Boxing is a sport that comprises a wide variety of integrated offensive, defensive and counter‐attack skills performed in an unpredictable environment. Mastering the variety of complex motor skills (CMS) that are required in a boxing match allows the player to employ the best motor performance in most positions of the actual game. This study aimed to assess the associations between implementing CMS versus simple motor skill (SMS) training and the subsequent changes in physical, technical and technical performance effectiveness (TPE) variables in junior boxers. We employed an experimental design that comprised two groups (each 20 males, mean age = 15.22±0.62 years). For 12 weeks, intervention boxers received CMS training, while controls received traditional SMS training. Physical, technical and TPE variables were measured before and after the training programs. Although the two groups were of similar abilities at baseline, there were statistically significant differences (P<0.05) between the intervention and control boxers in the post measures, to the advantage of the intervention group. In terms of absolute (i.e. differences in) or relative (i.e. ratios of) improvements, the intervention group exhibited more favourable values across the variables, and better performance. Developing CMS of junior boxers could contribute positively to their physical and technical abilities, and enhance their TPE.
Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region
Authors: Ivanovs Andrejs , Rybtsov Stanislav , Welch Lindsey , Anderson Richard A. , Turner Marc L. , Medvinsky Alexander
Published: November 2011

Hematopoietic stem cells (HSCs) emerge during embryogenesis and maintain hematopoiesis in the adult organism. Little is known about the embryonic development of human HSCs. We demonstrate that human HSCs emerge first in the aorta-gonad-mesonephros (AGM) region, specifically in the dorsal aorta, and only later appear in the yolk sac, liver, and placenta. AGM region cells transplanted into immunodeficient mice provide long-term high level multilineage hematopoietic repopulation. Human AGM region HSCs, although present in low numbers, exhibit a very high self-renewal potential. A single HSC derived from the AGM region generates at least 300 daughter HSCs in primary recipients, which disseminate throughout the entire recipient bone marrow and are retransplantable. These findings highlight the vast regenerative potential of the earliest human HSCs and set a new standard for in vitro generation of HSCs from pluripotent stem cells for the purpose of regenerative medicine.
Theta correspondences for 𝐺𝑆𝑝(4)
Authors: Gan Wee , Takeda Shuichiro
Published: November 2011

We explicitly determine the theta correspondences for

GSp
4

\operatorname {GSp}_4

and orthogonal similitude groups associated to various quadratic spaces of rank

4
4

and

6
6

. The results are needed in our proof of the local Langlands correspondence for

GSp
4

\operatorname {GSp}_4

.
Genotype and Approved Fungicide Evaluation for Reducing Leaf Spot Diseases in Organically-Managed Peanut
Authors: Wann Dylan Q. , Tubbs R. Scott , Culbreath Albert K.
Published: November 2011

Growers interested in organic peanut (Arachis hypogaea) production need information to identify genotypes and acceptable fungicides for control of early and late leaf spot where synthetic pesticide applications are absent. Field trials were conducted in 2008-2010 to evaluate eleven peanut genotypes for leaf spot resistance and yield potential under organic management. CRSP 983 and Georganic demonstrated the greatest resistance to early and late leaf spot (18 to 59% and 34 to 52% defoliation, respectively), but Florida-07, Georgia-06G, and Tifguard produced the largest yields (2454 to 5424 kg/ha, 3758 kg/ha, and 1760 to 4030 kg/ha, respectively). Tifguard exhibited the best combination of stand establishment, disease resistance, and yield potential of all genotypes and would be a strong option for growers pursuing organic production. Florida-07 and Georgia-06G are also formidable options. A secondary objective was to evaluate the efficacy of three approved fungicides for leaf spot control on peanut under organic management. Copper sulfate + Bacillus subtilis reduced leaf spot defoliation compared to the control. Yet, all three fungicides improved yields under heavy leaf spot pressure. Combining high-yielding, disease-resistant cultivars and organically approved fungicides can significantly improve leaf spot management and yield potential of peanut under organic management.

Accepted for publication 2 September 2011. Published 27 October 2011.
A New Report for Downy Mildew [(Hyaloperonospora camelinae Gäum.) Göker, Voglmayr, Riethm., M. Weiss & Oberw. 2003] of Camelina [Camelina sativa (L.) Crantz] in the High Plains of the United States
Authors: Harveson Robert M. , Santra Dipak K. , Putnam Melodie L. , Curtis Marc , Pavlista Alexander D.
Published: November 2011

Camelina is a new oilseed crop in Nebraska with good potential as a source of biodiesel. While evaluating cultivars for adaptability and yield potential, an epidemic of downy mildew was observed in research plots in Scottsbluff, NE. The pathogen was identified as Hyaloperonospora camelinae through morphological characteristics and PCR assays. This is the first substantiated report for this disease in the High Plains of the United States.

Accepted for publication 20 September 2011. Published 14 October 2011.
Leaf Spot of Pinto Bean Caused by a Long-beaked Alternaria in Southeastern Arizona
Authors: Garber Nicholas P. , Olsen Mary W.
Published: November 2011

This report identifies an Alternaria disease affecting pinto beans in incidence in Arizona. The similarity of disease symptoms and morphology of the pathogen to a recently characterized Alternaria and its disease of bean in Brazil causes concern about its potentially damaging effects on pinto bean production in Arizona.

Accepted for publication 20 September 2011. Published 18 October 2011.
The Potato Corky Ringspot Pathogen, Tobacco rattle virus, Occurs in Native Habitats in Minnesota
Authors: Lockhart Benham E. , Mason Shauna L.
Published: November 2011

When corky ringspot of potato, caused by Tobacco rattle virus, was first reported in Minnesota in 2008, it was thought that TRV did not occur naturally in Minnesota. Results reported here indicate that TRV occurs in Minnesota in areas with no known history of cultivation to potatoes or other crops, that these TRV isolates are variable, and that some are similar to virus isolated from potato with corky ringspot symptoms. These data suggest that corky ringspot incidence in Minnesota is due to the presence of endemic rather than introduced sources of TRV.

Accepted for publication 10 September 2011. Published 28 October 2011.
Role of the Inflammasome, IL-1β, and IL-18 in Bacterial Infections
Authors: Sahoo Manoranjan , Ceballos-Olvera Ivonne , del Barrio Laura , Re Fabio
Published: November 2011

The inflammasome is an important innate immune pathway that regulates at least two host responses protective against infections: (1) secretion of the proinflammatory cytokines IL-1βand IL-18 and (2) induction of pyroptosis, a form of cell death. Inflammasomes, of which different types have been identified, are multiprotein complexes containing pattern recognition receptors belonging to the Nod-like receptor family or the PYHIN family and the protease caspase-1. The molecular aspects involved in the activation of different inflammasomes by various pathogens are being rapidly elucidated, and their role during infections is being characterized. Production of IL-1βand IL-18 and induction of pyroptosis of the infected cell have been shown to be protective against many infectious agents. Here, we review the recent literature concerning inflammasome activation in the context of bacterial infections and identify important questions to be answered in the future.
Deep-transcriptome and ribonome sequencing redefines the molecular networks of pluripotency and the extracellular space in human embryonic stem cells
Authors: Kolle Gabriel , Shepherd Jill L. , Gardiner Brooke , Kassahn Karin S. , Cloonan Nicole , Wood David L.A. , Nourbakhsh Ehsan , Taylor Darrin F. , Wani Shivangi , Chy Hun S. , Zhou Qi , McKernan Kevin , Kuersten Scott , Laslett Andrew L. , Grimmond Sean M.
Published: November 2011

Recent RNA-sequencing studies have shown remarkable complexity in the mammalian transcriptome. The ultimate impact of this complexity on the predicted proteomic output is less well defined. We have undertaken strand-specific RNA sequencing of multiple cellular RNA fractions (>20 Gb) to uncover the transcriptional complexity of human embryonic stem cells (hESCs). We have shown that human embryonic stem (ES) cells display a high degree of transcriptional diversity, with more than half of active genes generating RNAs that differ from conventional gene models. We found evidence that more than 1000 genes express long 5′ and/or extended 3′UTRs, which was confirmed by “virtual Northern” analysis. Exhaustive sequencing of the membrane-polysome and cytosolic/untranslated fractions of hESCs was used to identify RNAs encoding peptides destined for secretion and the extracellular space and to demonstrate preferential selection of transcription complexity for translation in vitro. The impact of this newly defined complexity on known gene-centric network models such as the Plurinet and the cell surface signaling machinery in human ES cells revealed a significant expansion of known transcript isoforms at play, many predicting possible alternative functions based on sequence alterations within key functional domains.
Locus- and domain-dependent control of DNA methylation at mouse B1 retrotransposons during male germ cell development
Authors: Ichiyanagi Kenji , Li Yungfeng , Watanabe Toshiaki , Ichiyanagi Tomoko , Fukuda Kei , Kitayama Junko , Yamamoto Yasuhiro , Kuramochi-Miyagawa Satomi , Nakano Toru , Yabuta Yukihiro , Seki Yoshiyuki , Saitou Mitinori , Sasaki Hiroyuki
Published: November 2011

In mammals, germ cells undergo striking dynamic changes in DNA methylation during their development. However, the dynamics and mode of methylation are poorly understood for short interspersed elements (SINEs) dispersed throughout the genome. We investigated the DNA methylation status of mouse B1 SINEs in male germ cells at different developmental stages. B1 elements showed a large locus-to-locus variation in methylation; loci close to RNA polymerase II promoters were hypomethylated, while most others were hypermethylated. Interestingly, a mutation that eliminates Piwi-interacting RNAs (piRNAs), which are involved in methylation of long interspersed elements (LINEs), did not affect the level of B1 methylation, implying a piRNA-independent mechanism. Methylation at B1 loci in SINE-poor genomic domains showed a higher dependency on the de novo DNA methyltransferase DNMT3A but not on DNMT3B, suggesting that DNMT3A plays a major role in methylation of these domains. We also found that many genes specifically expressed in the testis possess B1 elements in their promoters, suggesting the involvement of B1 methylation in transcriptional regulation. Taken altogether, our results not only reveal the dynamics and mode of SINE methylation but also suggest how the DNA methylation profile is created in the germline by a pair of DNA methyltransferases.
Activating Photoactivatable Proteins with Laser Light to Visualize Membrane Systems and Membrane Traffic in Living Cells
Authors: Snapp Erik Lee , Lajoie Patrick
Published: November 2011

Eukaryotic cells are composed of an intricate system of internal membranes that are organized into different compartments—including the endoplasmic reticulum (ER), the nuclear envelope, the Golgi complex (GC), lysosomes, endosomes, caveolae, mitochondria, and peroxisomes—that perform specialized tasks within the cell. The localization and dynamics of intracellular compartments are now being studied in living cells because of the availability of green fluorescent protein (GFP)-fusion proteins and recent advances in fluorescent microscope imaging systems, such as the confocal laser-scanning microscope (CLSM). This protocol describes the steps for activating one of the first photoactivatable proteins, PA-GFP.
Measuring Neuronal Population Activity Using 3D Laser Scanning
Authors: Kampa Björn M. , Göbel Werner , Helmchen Fritjof
Published: November 2011

Neural tissue is organized in three-dimensional (3D) networks of neuronal and glial cell populations. To understand the functional organization of these networks, it is desirable to achieve 3D activity measurements from large cell populations in intact tissue with high temporal resolution. Repeated acquisition of image stacks with standard laser-scanning microscopes is too slow. This protocol describes fast 3D calcium imaging in the living brain using mechanical laser scanning with standard galvanometric mirrors and a piezoelectric focusing element. The purpose of 3D laser scanning is to create a 3D line scan that samples relatively homogenously from a particular observation volume. The spatial resolution of this approach is low, except along the line. However, the main goal is not to resolve subcellular structures, but rather to hit as many cell bodies as possible within the volume. In this manner, local network activity can be inferred from the somatic calcium signals of a significant fraction of the cell population. With a sinusoidal swinging microscope objective as a constraint, 3D scan trajectories are generated that sample fluorescence signals from the majority of cells within a cuboidal volume. Measurements with 10-Hz temporal resolution can be achieved for population calcium signals from several hundreds of identified neurons and glial cells within cuboids with side lengths of ∼250 µm. An example cellular 3D orientation map of the rat visual cortex is presented. This 3D laser-scanning technique enables direct observation of in vivo neural network dynamics in cell populations of substantial size.
In Vitro Transfection Using Cyclodextrin-Containing Polycations
Authors: Heidel Jeremy D.
Published: November 2011

Numerous nonviral systems have been developed for the delivery of nucleic acids to cultured cells and to particular cell types in vivo. These systems vary with regard to their toxicity, immunogenicity, and ability to target particular cell surface receptors and/or cell types. A class of linear cationic polymers containing the sugar β-cyclodextrin has been shown to be effective at delivering a variety of nucleic acids in vivo, including plasmid DNA, DNAzymes, and short interfering RNAs (siRNAs). This protocol describes a procedure for the use of cyclodextrin-containing polycations in vitro. For in vitro transfection, salt stabilization and cell targeting are unnecessary, so polyplexes consist of cyclodextrin-containing polycations and nucleic acids only.
Imaging of Membrane Systems and Membrane Traffic in Living Cells
Authors: Snapp Erik Lee , Lajoie Patrick
Published: November 2011

Eukaryotic cells are composed of an intricate system of internal membranes that are organized into different compartments—including the endoplasmic reticulum (ER), the nuclear envelope, the Golgi complex (GC), lysosomes, endosomes, caveolae, mitochondria, and peroxisomes—that perform specialized tasks within the cell. The localization and dynamics of intracellular compartments are now being studied in living cells because of the availability of green fluorescent protein (GFP)-fusion proteins and recent advances in fluorescent microscope imaging systems. Results using these techniques are revealing how intracellular compartments maintain their steady-state organization and distributions, how they undergo growth and division, and how they transfer protein and lipid components between themselves through the formation and trafficking of membrane transport intermediates. This article describes methods using GFP-fusion proteins to visualize the behavior of organelles and to track membrane-bound transport intermediates moving between them. Practical issues related to the construction and expression of GFP-fusion proteins are discussed first. These are essential for optimizing the brightness and expression levels of GFP-fusion proteins so that intracellular membrane-bound structures containing these fusion proteins can be readily visualized. Next, techniques for performing time-lapse imaging using a confocal laser-scanning microscope (CLSM) are detailed, including the use of photobleaching to highlight organelles and transport intermediates. Methods for the acquisition and analysis of data are then discussed. Finally, commonly used and exciting new approaches for perturbing membrane traffic are outlined.
Comparative Genomic Hybridization to Detect Variation in the Copy Number of Large DNA Segments
Authors: Holcomb Ilona N. , Trask Barbara J.
Published: November 2011

Array comparative genomic hybridization (CGH) is an excellent tool to scan the genome for copy number variations (CNVs) when used conscientiously. This article is intended to provide an understanding of the basic principles of array CGH and the different options available to the user to design their array CGH experiments. Specifically, the six subsections discuss the different array platforms available, test and reference DNA preparation, reference DNA choice, the basics of hybridization, data processing, and our current understanding of CNVs in the human genome.
Antagonistic Action of Strigolactone and Cytokinin in Bud Outgrowth Control
Authors: Dun Elizabeth A. , de Saint Germain Alexandre , Rameau Catherine , Beveridge Christine A.
Published: November 2011

Cytokinin (CK) has long been implicated as a promoter of bud outgrowth in plants, but exactly how this is achieved in coordination with other plant hormones is unclear. The recent discovery of strigolactones (SLs) as the long-sought branch-inhibiting hormone allowed us to test how CK and SL coordinately regulate bud outgrowth in pea (Pisum sativum). We found that SL-deficient plants are more sensitive to stimulation of bud growth by low concentrations of locally applied CK than wild-type plants. Furthermore, in contrast with SL mutant plants, buds of wild-type plants are almost completely resistant to stimulation by CK supplied to the vasculature. Regardless of whether the exogenous hormones were supplied locally or to the xylem stream, SL and CK acted antagonistically on bud outgrowth. These data suggest that SLs do not affect the delivery of CK to axillary buds and vice versa. Rather, these data combined with dose-response experiments suggest that SLs and CK can act directly in buds to control their outgrowth. These hormones may converge at a common point in the bud outgrowth regulatory pathway. The expression of pea BRANCHED1, a TCP transcription factor expressed strongly in buds and thought to act downstream of SLs in shoot branching, is regulated by CK and SL without a requirement for protein synthesis and in a manner that correlates with observed bud growth responses.
Anti‐inflammatory properties of intestinal Bifidobacterium strains isolated from healthy infants
Authors: Khokhlova Ekaterina V. , Smeianov Vladimir V. , Efimov Boris A. , Kafarskaia Lyudmila I. , Pavlova Svetlana I. , Shkoporov Andrei N.
Published: November 2011

Certain Bifidobacterium strains have been shown to inhibit inflammatory responses in intestinal epithelial cells. However, the precise mechanisms of these effects, including the chemical nature of the active compounds, remain to be elucidated. Here partial characterization of the anti‐inflammatory properties of Bifidobacterium strains isolated from feces of healthy infants is reported. It was found that conditioned media (CM) of all strains studied are capable of attenuating tumor necrosis factor‐α (TNF‐α) and lipopolysaccharide‐ (LPS) induced inflammatory responses in the HT‐29 cell line. In contrast, neither killed bifidobacterial cells, nor cell‐free extracts showed such activities. Further investigations resulted in attribution of this activity to heat‐stable, non‐lipophilic compound(s) resistant to protease and nuclease treatments and of molecular weight less than 3  kDa. The anti‐inflammatory effects were dose‐ and time‐dependent and associated with inhibition of IκB phosphorylation and nuclear factor‐κ light chain enhancer of activated B cells (NF‐κB)‐dependent promoter activation. The combined treatments of cells with CMs and either LPS or TNF‐α, but not with CMs alone, resulted in upregulation of transforming growth factor‐β1, IκBζ, and p21CIP mRNAs. Our data suggest certain species‐specificities of the anti‐inflammatory properties of bifidobacteria. This observation should prompt additional validation studies using larger set of strains and employing the tools of comparative genomics.
Microbial resistance in relation to catalase activity to oxidative stress induced by photolysis of hydrogen peroxide
Authors: Nakamura Keisuke , Kanno Taro , Mokudai Takayuki , Iwasawa Atsuo , Niwano Yoshimi , Kohno Masahiro
Published: November 2011

The purpose of the present study was to evaluate the mechanism of microbial resistance to oxidative stress induced by photolysis of hydrogen peroxide (H2O2) in relation to microbial catalase activity. In microbicidal tests, Staphylococcus aureus and Candida albicans were killed and this was accompanied by production of hydroxyl radicals. C. albicans was more resistant to hydroxyl radicals generated by photolysis of H2O2 than was S. aureus. A catalase activity assay demonstrated that C. albicans had stronger catalase activity; accordingly, catalase activity could be one of the reasons for the resistance of the fungus to photolysis of H2O2. Indeed, it was demonstrated that C. albicans with strong catalase activity was more resistant to photolysis of H2O2 than that with weak catalase activity. Kinetic analysis using a modified Lineweaver‐Burk plot also demonstrated that the microorganisms reacted directly with hydroxyl radicals and that this was accompanied by decomposition of H2O2. The results of the present study suggest that the microbicidal effects of hydroxyl radicals generated by photolysis of H2O2 can be alleviated by decomposition of H2O2 by catalase in microorganisms.
Effects of ketoconazole and valproic acid on the pharmacokinetics of the next generation NNRTI, lersivirine (UK‐453,061), in healthy adult subjects
Authors: Langdon Grant , Davis John , Layton Gary , Chong Chew‐Lan , Weissgerber Georges , Vourvahis Manoli
Published: November 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Lersivirine (UK‐453,061) is predominantly cleared by glucuronidation (UGT2B7) and oxidation via cytochrome P450 (CYP) 3A4.

• Lersivirine metabolism, and thus pharmacokinetics, may be affected by concomitant administration of drugs affecting CYP3A4 and UGT2B7.

• Ketoconazole is a potent inhibitor of CYP3A4 and an inhibitor of UGT2B7. Valproic acid is a potent inhibitor of UGT2B7.

WHAT THIS STUDY ADDS

• Combined inhibition of CYP3A4 and UGT2B7 with ketoconazole increases the exposure of lersivirine, and may warrant lersivirine dose adjustment to compensate for this interaction.

• Inhibition of UGT2B7 with valproic acid does not have a substantial effect on lersivirine pharmacokinetics.

AIMS

To investigate the effect of inhibitors of cytochrome P450 (CYP) 3A4 and glucuronidation (UGT2B7) on the pharmacokinetics of lersivirine (UK‐453,061), a next generation non‐nucleoside reverse transcriptase inhibitor with a unique resistance profile, and to investigate the safety and tolerability of co‐administration of lersivirine with these inhibitors.

METHODS

Two open‐label, randomized, placebo‐controlled, crossover studies were conducted in healthy subjects. Study 1 investigated the effect of ketoconazole (400 mg once daily) on the pharmacokinetics of lersivirine (250 mg once daily). Subjects received ketoconazole 400 mg once daily or placebo on days 1–2 and received lersivirine 250 mg once daily and ketoconazole 400 mg once daily or placebo on days 3–9. Study 2 investigated the effect of valproic acid (VPA, sodium valproate, 1000 mg once daily) on the PK of lersivirine (500 mg once daily). On days 1–7, subjects received lersivirine 500 mg once daily plus either VPA 1000 mg or placebo.

RESULTS

Compared with lersivirine alone, co‐administration with ketoconazole increased the lersivirine mean area under the curve (AUC(0,24 h)) and maximum plasma concentration (Cmax) by 82% (90% CI 74%, 91%) and 61% (90% CI 41%, 83%), respectively. VPA increased the mean lersivirine AUC(0,24 h) by 25% (90% CI 16%, 35%), with little effect on Cmax (2.5%, 90% CI −9%, 16%). There were no serious adverse events and no treatment‐related discontinuations from either study.

CONCLUSIONS

Inhibition of CYP3A4 and UGT2B7 by ketoconazole increased lersivirine exposure. Inhibition of UGT2B7‐mediated glucuronidation by VPA had a modest effect on lersivirine exposure. Co‐administration of lersivirine with either ketoconazole or VPA appeared to be well tolerated.
What helps children to be more active and less sedentary? Perceptions of mothers living in disadvantaged neighbourhoods
Authors: Veitch J. , Hume C. , Salmon J. , Crawford D. , Ball K.
Published: November 2011

Background Increasing children's participation in physical activity and decreasing time spent in sedentary behaviours is of great importance to public health. Despite living in disadvantaged neighbourhoods, some children manage to engage in health‐promoting physical activity and avoid high levels of screen‐based activities (i.e. watching TV, computer use and playing electronic games). Understanding how these children manage to do well and whether there are unique features of their home or neighbourhood that explain their success is important for informing strategies targeting less active and more sedentary children. The aim of this qualitative study was to gain in‐depth insights from mothers regarding their child's resilience to low physical activity and high screen‐time.

Methods Semi‐structured face‐to‐face interviews were conducted with 38 mothers of children who lived in disadvantaged neighbourhoods in urban and rural areas of Victoria, Australia. The interviews were designed to gain in‐depth insights about perceived individual, social and physical environmental factors influencing resilience to low physical activity and high screen‐time.

Results Themes relating to physical activity that emerged from the interviews included: parental encouragement, support and modelling; sports culture in a rural town; the physical home and neighbourhood environment; child's individual personality; and dog ownership. Themes relating to screen‐time behaviours encompassed: parental control; and child's individual preferences.

Conclusions The results offer important insights into potential avenues for developing ‘resilience’ and increasing physical activity and reducing screen‐time among children living in disadvantaged neighbourhoods. In light of the negative effects of low physical activity and high levels of screen‐time on children's health, this evidence is urgently needed.
Hypochlorous acid regulates neutrophil extracellular trap release in humans
Authors: Palmer L J , Cooper P R , Ling M R , Wright H J , Huissoon A , Chapple I L C
Published: November 2011

Neutrophil extracellular traps (NETs) comprise extracellular chromatin and granule protein complexes that immobilize and kill bacteria. NET release represents a recently discovered, novel anti-microbial strategy regulated non-exclusively by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase generation of reactive oxygen intermediates (ROIs), particularly hydrogen peroxide. This study aimed to characterize the role of ROIs in the process of NET release and to identify the dominant ROI trigger. We employed various enzymes, inhibitors and ROIs to record their effect fluorometrically on in vitro NET release by human peripheral blood neutrophils. Treatment with exogenous superoxide dismutase (SOD) supported the established link between hydrogen peroxide and NET production. However, treatment with myeloperoxidase inhibitors and direct addition of hypochlorous acid (HOCl; generated in situ from sodium hypochlorite) established that HOCl was a necessary and sufficient ROI for NET release. This was confirmed by the ability of HOCl to stimulate NET release in chronic granulomatous disease (CGD) patient neutrophils which, due to the lack of a functional NADPH oxidase, also lack the capacity for NET release in response to classical stimuli. Moreover, the exogenous addition of taurine, abundantly present within the neutrophil cytosol, abrogated NET production stimulated by phorbol myristate acetate (PMA) and HOCl, providing a novel mode of cytoprotection by taurine against oxidative stress by taurine.
Upscaling methane fluxes from closed chambers to eddy covariance based on a permafrost biogeochemistry integrated model
Authors: Zhang Yu , Sachs Torsten , Li Changsheng , Boike Julia
Published: November 2011

Northern peatlands are a major natural source of methane (CH4) to the atmosphere. Permafrost conditions and spatial heterogeneity are two of the major challenges for estimating CH4 fluxes from the northern high latitudes. This study reports the development of a new model to upscale CH4 fluxes from plant communities to ecosystem scale in permafrost peatlands by integrating an existing biogeochemical model DeNitrification‐DeComposition (DNDC) with a permafrost model Northern Ecosystem Soil Temperature (NEST). A new ebullition module was developed to track the changes of bubble volumes in the soil profile based on the ideal gas law and Henry's law. The integrated model was tested against observations of CH4 fluxes measured by closed chambers and eddy covariance (EC) method in a polygonal permafrost area in the Lena River Delta, Russia. Results from the tests showed that the simulated soil temperature, summer thaw depths and CH4 fluxes were in agreement with the measurements at the five chamber observation sites; and the modeled area‐weighted average CH4 fluxes were similar to the EC observations in seasonal patterns and annual totals although discrepancy existed in shorter time scales. This study indicates that the integrated model, NEST–DNDC, is capable of upscaling CH4 fluxes from plant communities to larger spatial scales.
Vulnerability of riparian ecosystems to elevated CO2 and climate change in arid and semiarid western North America
Authors: Perry Laura G. , Andersen Douglas C. , Reynolds Lindsay V. , Nelson S. Mark , Shafroth Patrick B.
Published: November 2011

Riparian ecosystems, already greatly altered by water management, land development, and biological invasion, are being further altered by increasing atmospheric CO2 concentrations ([CO2]) and climate change, particularly in arid and semiarid (dryland) regions. In this literature review, we (1) summarize expected changes in [CO2], climate, hydrology, and water management in dryland western North America, (2) consider likely effects of those changes on riparian ecosystems, and (3) identify critical knowledge gaps. Temperatures in the region are rising and droughts are becoming more frequent and intense. Warmer temperatures in turn are altering river hydrology: advancing the timing of spring snow melt floods, altering flood magnitudes, and reducing summer and base flows. Direct effects of increased [CO2] and climate change on riparian ecosystems may be similar to effects in uplands, including increased heat and water stress, altered phenology and species geographic distributions, and disrupted trophic and symbiotic interactions. Indirect effects due to climate‐driven changes in streamflow, however, may exacerbate the direct effects of warming and increase the relative importance of moisture and fluvial disturbance as drivers of riparian ecosystem response to global change. Together, climate change and climate‐driven changes in streamflow are likely to reduce abundance of dominant, native, early‐successional tree species, favor herbaceous species and both drought‐tolerant and late‐successional woody species (including many introduced species), reduce habitat quality for many riparian animals, and slow litter decomposition and nutrient cycling. Climate‐driven changes in human water demand and associated water management may intensify these effects. On some regulated rivers, however, reservoir releases could be managed to protect riparian ecosystem. Immediate research priorities include determining riparian species' environmental requirements and monitoring riparian ecosystems to allow rapid detection and response to undesirable ecological change.
Impacts of atmospheric nitrogen deposition: responses of multiple plant and soil parameters across contrasting ecosystems in long‐term field experiments
Authors: Phoenix Gareth K. , Emmett Bridget A. , Britton Andrea J. , Caporn Simon J. M. , Dise Nancy B. , Helliwell Rachel , Jones Laurence , Leake Jonathan R. , Leith Ian D. , Sheppard Lucy J. , Sowerby Alwyn , Pilkington Michael G. , Rowe Edwin C. , Ashmore Mike R. , Power Sally A.
Published: November 2011

Atmospheric nitrogen (N) deposition is a global and increasing threat to biodiversity and ecosystem function. Much of our current understanding of N deposition impacts comes from field manipulation studies, although interpretation may need caution where simulations of N deposition (in terms of dose, application rate and N form) have limited realism. Here, we review responses to simulated N deposition from the UKREATE network, a group of nine experimental sites across the UK in a diversity of heathland, grassland, bog and dune ecosystems which include studies with a high level of realism and where many are also the longest running globally on their ecosystem type. Clear responses were seen across the sites with the greatest sensitivity shown in cover and species richness of bryophytes and lichens. Productivity was also increased at sites where N was the limiting nutrient, while flowering also showed high sensitivity, with increases and declines seen in dominant shrub and forb species, respectively. Critically, these parameters were responsive to some of the lowest additional loadings of N (7.7–10 kg ha−1 yr−1) showing potential for impacts by deposition rates seen in even remote and ‘unpolluted’ regions of Europe. Other parameters were less sensitive, but nevertheless showed response to higher doses. These included increases in soil %N and ‘plant available’ KCl extractable N, N cycling rates and acid–base status. Furthermore, an analysis of accumulated dose that quantified response against the total N input over time suggested that N impacts can ‘build up’ within an ecosystem such that even relatively low N deposition rates can result in ecological responses if continued for long enough. Given the responses have important implications for ecosystem structure, function, and recovery from N loading, the clear evidence for impacts at relatively low N deposition rates across a wide range of habitats is of considerable concern.
Optimising the dose of oral midazolam sedation for dental procedures in children: a prospective, randomised, and controlled study
Authors: SOMRI MOSTAFA , PARISINOS CONSTANTINOS A. , KHAROUBA JOHNY , CHERNI NAOMI , SMIDT AMI , ABU RAS ZACKARIYA , DARAWSHI GEITH , GAITINI LUIS A.
Published: November 2011

International Journal of Paediatric Dentistry 2012; 22: 271–279

Background.  Midazolam sedation poses a significant dilemma in paediatric dentistry, which is to find out the optimal dosing with minimal undesirable adverse events. In this study, we aimed to compare the effect of three doses of oral midazolam (0.5, 0.75, and 1 mg/kg) on the sedative state and cooperative behaviour of children during dental treatment. We further compared completion rates, parent satisfaction, and all adverse events.

Design.  Ninety children aged 3–10 years were randomised to three equal groups. Groups A, B, and C received 0.5, 0.75, and 1 mg/kg of oral midazolam, respectively. Levels of sedation, cooperative behaviour, procedures completion rates, parent satisfaction, and adverse events were prospectively recorded.

Results.  Sedation scores in B and C were higher (P < 0.001) than in A. Cooperation scores (CS) in B and C were higher (P < 0.001) than in A. Significant increase in completion rates was observed between A and C (P = 0.025). Parent satisfaction was greater in B and C (P < 0.001) compared to A. Adverse events were higher in C (P < 0.05) than in A or B.

Conclusion.  Amount of 0.75 mg/kg oral midazolam appears to be the optimal oral dose in terms of effectiveness, acceptability, and safety for dental treatments in paediatric patients, when administered by an experienced, paediatric anaesthetist.
Species richness effects on ecosystem multifunctionality depend on evenness, composition and spatial pattern
Authors: Maestre Fernando T. , Castillo‐Monroy Andrea P. , Bowker Matthew A. , Ochoa‐Hueso Raúl
Published: November 2011

1. Recent studies have suggested that the simultaneous maintenance of multiple ecosystem functions (multifunctionality) is positively supported by species richness. However, little is known regarding the relative importance of other community attributes (e.g. spatial pattern, species evenness) as drivers of multifunctionality.

2. We conducted two microcosm experiments using model biological soil crust communities dominated by lichens to: (i) evaluate the joint effects and relative importance of changes in species composition, spatial pattern (clumped and random distribution of lichens), evenness (maximal and low evenness) and richness (from two to eight species) on soil functions related to nutrient cycling (β‐glucosidase, urease and acid phosphatase enzymes,in situN availability, total N, organic C, and N fixation), and (ii) assess how these community attributes affect multifunctionality.

3. Species richness, composition and spatial pattern affected multiple ecosystem functions (e.g. organic C, total N, N availability, β‐glucosidase activity), albeit the magnitude and direction of their effects varied with the particular function, experiment and soil depth considered. Changes in species composition had effects on organic C, total N and the activity of β‐glucosidase. Significant species richness × evenness and spatial pattern × evenness interactions were found when analysing functions such as organic C, total N and the activity of phosphatase.

4. The probability of sustaining multiple ecosystem functions increased with species richness, but this effect was largely modulated by attributes such as species evenness, composition and spatial pattern. Overall, we found that model communities with high species richness, random spatial pattern and low evenness increased multifunctionality.

5. Synthesis. Our results illustrate how different community attributes have a diverse impact on ecosystem functions related to nutrient cycling, and provide new experimental evidence illustrating the importance of the spatial pattern of organisms on ecosystem functioning. They also indicate that species richness is not the only biotic driver of multifunctionality, and that particular combinations of community attributes may be required to maximize it.
Hospital utilization and costs for spinal cord stimulation compared with enhanced external counterpulsation for refractory angina pectoris
Authors: Bondesson Susanne M. , Jakobsson Ulf , Edvinsson Lars , Hallberg Ingalill Rahm
Published: November 2011

Rationale, aims and objectives  The aim of this study was to compare acute hospital utilization and costs for patients with refractory angina pectoris undergoing spinal cord stimulation (SCS) versus enhanced external counterpulsation (EECP).

Method  Seventy‐three persons were included in this register study. The acute hospital utilization and costs for SCS and EECP were followed over a period from 12 months before treatment to 24 months after treatment using Patient Administrative Support in Skåne for publicly organized care.

Results  SCS was significantly more expensive than EECP (P < 0.001). Both SCS and EECP entailed fewer days of hospitalization for coronary artery disease in the 12‐month follow‐up compared with the 12 months preceding treatment. Patients treated with EECP showed an association between reduced hospital admissions and an improved Canadian Cardiovascular Society classification class compared with 1 year before treatment. A significant reduction in cost was seen in both the SCS group (P = 0.018 and P = 0.001, respectively) and the EECP group (P = 0.002 and P = 0.045, respectively) during 12 and 24 months of follow‐up compared with before treatment. There were no significant differences between the groups for hospitalization days or admissions, including costs, at the different follow‐ups.

Conclusions  Cost‐effective treatment modalities such as SCS and EECP are valuable additions to medical and revascularization therapy in patients with refractory angina pectoris. Pre‐existing conditions and the patient's preferences should be taken in consideration when clinicians choose between treatments for this group of patients.