bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of buprenorphine following intravenous and intramuscular administration in male rhesus macaques (Macaca mulatta)
Authors: Kelly K. R. , Pypendop B. H. , Christe K. L.
Published: March 2014

This study reports the pharmacokinetics of buprenorphine in conscious rhesus macaques (Macaca mulatta) after intravenous (i.v.) and intramuscular (i.m.) administration. Four healthy, opioid‐naïve, socially housed, adult male macaques were used. Buprenorphine (0.03 mg/kg) was administered intravenously as a bolus or intramuscularly on separate occasions. Blood samples were collected prior to, and up to 24 h, postadministration. Serum buprenorphine concentrations were analyzed with liquid chromatography–mass spectrometry. Noncompartmental pharmacokinetic analysis was performed with commercially available software. Mean residence time in the i.v. study as compared to the i.m. study was 177 (159–189) vs. 185 (174–214) min, respectively [median (range)]. In the i.v. study, concentration back‐extrapolated to time zero was found to be 33.0 (16.8–57.0) ng/mL [median (range)]. On the other hand, the maximum serum concentration found in the i.m. study was 11.8 (6.30–14.8) ng/mL [median (range)]. Rhesus macaques maintained concentrations >0.10 ng/mL for over 24 h in the i.v. study and over 12 h in the i.m. study. Bioavailability was found to be 68.1 (59.3–71.2)% [median (range)]. No significant adverse effects were observed in the monkeys at the 0.03 mg/kg dose of buprenorphine during either study.
Reliability of causality assessment for drug, herbal and dietary supplement hepatotoxicity in the Drug‐Induced Liver Injury Network (DILIN)
Authors: Hayashi Paul H. , Barnhart Huiman X. , Fontana Robert J. , Chalasani Naga , Davern Timothy J. , Talwalkar Jayant A. , Reddy K. Rajender , Stolz Andrew A. , Hoofnagle Jay H. , Rockey Don C.
Published: March 2014

Background & Aims

Because of the lack of objective tests to diagnose drug‐induced liver injury (DILI), causality assessment is a matter of debate. Expert opinion is often used in research and industry, but its test–retest reliability is unknown. To determine the test–retest reliability of the expert opinion process used by the Drug‐Induced Liver Injury Network (DILIN).

Methods

Three DILIN hepatologists adjudicate suspected hepatotoxicity cases to one of five categories representing levels of likelihood of DILI. Adjudication is based on retrospective assessment of gathered case data that include prospective follow‐up information. One hundred randomly selected DILIN cases were re‐assessed using the same processes for initial assessment but by three different reviewers in 92% of cases.

Results

The median time between assessments was 938 days (range 140–2352). Thirty‐one cases involved >1 agent. Weighted kappa statistics for overall case and individual agent category agreement were 0.60 (95% CI: 0.50–0.71) and 0.60 (0.52–0.68) respectively. Overall case adjudications were within one category of each other 93% of the time, while 5% differed by two categories and 2% differed by three categories. Fourteen per cent crossed the 50% threshold of likelihood owing to competing diagnoses or atypical timing between drug exposure and injury.

Conclusions

The DILIN expert opinion causality assessment method has moderate interobserver reliability but very good agreement within one category. A small but important proportion of cases could not be reliably diagnosed as ≥50% likely to be DILI.
Island bat diets: does it matter more who you are or where you live?
Authors: Sedlock Jodi L. , Krüger Frauke , Clare Elizabeth L.
Published: March 2014

Differences in body size, echolocation call frequency and location may result in diet partitioning among bat species. Comparisons between island populations are one way to evaluate these competing hypotheses. We conducted a species‐level diet analysis of three Rhinolophus and one Hipposideros species on the Philippine islands of Cebu, Bohol and Siquijor. We identified 655 prey (MOTUs) in the guano from 77 individual bats. There was a high degree of overlap among species' diets despite differences in body size and call frequency. For example, the diet of the 3 g‐Hipposideros pygmaeus (mean CF = 102 kHz) exhibited a diet overlap higher than expected by chance with all three Rhinolophus species, even the 13 g‐Rhinolophus inops (mean CF = 54 kHz). We observed more convergence in diet between Rhinolophus species and H. pygmaeus than between Rhinolophus species themselves, which may be explained by the broad diet of H. pygmaeus. There was less dietary overlap between Rhinolophus virgo from two islands than between R. virgo and congeners from Cebu. These data suggest that location causes convergence in diet, but specific species characteristics may drive niche specialization. The complex interplay between location and the perceptual ability of each species leads to a situation where simple explanations, for example body size, do not translate into predictable prey partitioning. In particular, our observations raise interesting questions about the foraging strategy and adaptability of the tiny H. pygmaeus.
Generation and Preliminary Characterization of Immortalized Cell Line Derived from Rat Lymphatic Capillaries
Authors: G. Romanova Liudmila , A. Hansen Eric , Lam Cornelius H.
Published: March 2014

Objective

Isolation of rodent endothelial cells from lymphatic capillaries with yields that allow extensive functional studies remains challenging due to low cell numbers, variable purity, and limited growth potential. The purpose of this study was the generation and preliminary characterization of rat lymphatic cell line with extended replicative capacity. This cell line is intended for in vitro studies of cellular transport in lymphatic endothelium and for in vivo experiments in rat animal models.

Methods

We created a novel rat lymphatic immortalized cell line, SV40‐LEC, using retroviral gene transfer of SV40 large T antigen. We confirmed expression of characteristic markers and then examined its growth and transport properties.

Results

SV40‐LECs demonstrated improved proliferative capacity, but retained morphological characteristics of lymphatic cells and expression of established lymphatic markers. The cells form capillary‐like network in vitro. SV40‐LEC monolayer has similar permeability to that of the primary initial lymphatics. Paracellular transport in SV40‐LECs is limited for substances >70 kDa. Barrier properties of the SV40‐LECs can be modulated by cyclic adenosine monophosphate and histamine, which are known to affect microvascular permeability.

Conclusion

The SV40‐LECs provide an excellent tool for in vitro studies of properties of lymphatic endothelium, and may be suitable for in vivo transplantation studies.
A Hybrid Pareto Frontier Generation Method for Trade‐Off Analysis in Transportation Asset Management
Authors: Bai Qiang , Ahmed Anwaar , Li Zongzhi , Labi Samuel
Published: March 2014

Trade‐off analysis, one of the key elements of transportation asset management (TAM), helps decision makers to not only quantify how different resource allocations affect system performance but also investigate the trade‐off relationships between cost and performance measures and between different performance measures. In the fast‐growing field of TAM, researchers are beginning to quantify the trade‐offs among the performance measures. A successful quantification of these trade‐offs is important for the practice because the highway agency decision makers responsible for project selection have long been stymied by a lack of knowledge of the extent to which different decisions lead to different performance trade‐offs. In a follow‐up to recent research efforts that have sought to address this issue, this article presents a further improved methodology to facilitate the analysis of trade‐offs in TAM. First, a general multiobjective optimization framework for TAM is established. Next, the developed hybrid method is presented, which is then shown to quicken the generation of Pareto frontiers for the purpose of conducting trade‐off analysis. Using a case study, the proposed hybrid method, which was implemented on a computer to generate Pareto frontiers, ultimately converged faster and generated better‐distributed Pareto frontiers compared to the NSGA II method of Pareto frontier generation in the TAM context. Using the generated Pareto frontiers, trade‐off analysis between cost and performance measures and between performance measures are demonstrated in this article.
Mannitol infusion immediately after reperfusion suppresses the development of focal cortical infarction after temporary cerebral ischemia in gerbils
Authors: Ito Umeo , Hakamata Yoji , Watabe Kazuhiko , Oyanagi Kiyomitsu
Published: March 2014

Previously we found that, after temporary cerebral ischemia, microvasculogenic secondary focal cerebral cortical ischemia occurred, caused by microvascular obstruction due to compression by swollen astrocytic end‐feet, resulting in focal infarction. Herein, we examined whether mannitol infusion immediately after restoration of blood flow could protect the cerebral cortex against the development of such an infarction. If so, the infusion of mannitol might improve the results of vascular reperfusion therapy. We selected stroke‐positive animals during the first 10 min after left carotid occlusion performed twice with a 5‐h interval, and allocated them into four groups: sham‐operated control, no‐treatment, mannitol‐infusion, and saline‐infusion groups. Light‐ and electron‐microscopic studies were performed on cerebral cortices of coronal sections prepared at the chiasmatic level, where the focal infarction develops abruptly in the area where disseminated selective neuronal necrosis is maturing. Measurements were performed to determine the following: (A) infarct size in HE‐stained specimens from all groups at 72 and 120 h after return of blood flow; (B) number of carbon‐black‐suspension‐perfused microvessels in the control and at 0.5, 3, 5, 8, 12 and 24 h in the no‐treatment and mannitol‐infusion groups; (C) area of astrocytic end‐feet; and (D) number of mitochondria in the astrocytic end‐feet in electron microscopic pictures taken at 5 h. The average decimal fraction area ratio of infarct size in the mannitol group was significantly reduced at 72 and 120 h, associated with an increased decimal fraction number ratio of carbon‐black‐suspension‐perfused microvessels at 3, 5 and 8 h, and a marked reduction in the size of the end‐feet at 5 h. Mannitol infusion performed immediately after restitution of blood flow following temporary cerebral ischemia remarkably reduced the size of the cerebral cortical focal infarction by decreasing the swelling of the end‐feet, thus preventing the microvascular compression and stasis and thereby microvasculogenic secondary focal cerebral ischemia.
Israeli–Palestinian Healthcare Partnerships: Advancing Multitrack Peacework After the Arab Spring
Authors: Davis Ryan G.
Published: March 2014

Israeli–Palestinian cooperation on healthcare initiatives demonstrates the potential for progress toward peace through nongovernmental partnerships while formal government negotiations falter. Health interventions create space for opposing groups to engage peacefully and collaboratively, but disagreement persists about the politicization of humanitarian assistance. Together with other sectors of society, the healthcare community can contribute to achieving and maintaining peace between Israelis and Palestinians as part of a multitrack peacework strategy. The Arab Spring's revitalization of democracy and civil society throughout the region creates opportunities for broad‐based, civilian‐motivated movements for change. Drawing on events during the 2008–2009 Gaza War and experiences with various healthcare programs, I describe three mechanisms by which peace can be advanced through health initiatives and review what evidence is available to support this approach.
Sea‐Dogs for Peace: An Exploration of Nonviolent Maritime Interventions for Peace and Justice
Authors: Rigby Andrew
Published: March 2014

Historically, nonviolent direct activists against oppression and injustice have sought to touch the emotions of targeted audiences by means of dramatic “image events.” Nowhere has this been more apparent than in the many examples of nonviolent maritime intervention where activists have taken to the sea to further their struggle against what they have defined as threats to human well‐being and the future of the planet. The history of such seaborne activism reveals an evolution from small‐scale initiatives through to larger‐scale “professional productions” involving nongovernmental organizations and transnational social movements. With the transformation of media technology and the growth of international networks of social movements and civil society organizations, we can anticipate an expansion of nonviolent maritime interventions by media‐savvy direct activists seeking to use the relative autonomy that can be enjoyed on the “high seas” in order to highlight issues of concern.
Protection and pathology during parasite infection: IL‐10 strikes the balance
Authors: Redpath S. A. , Fonseca N. M. , Perona‐Wright G.
Published: March 2014

The host response to infection requires an immune response to be strong enough to control the pathogen but also restrained, to minimize immune‐mediated pathology. The conflicting pressures of immune activation and immune suppression are particularly apparent in parasite infections, where co‐evolution of host and pathogen has selected many different compromises between protection and pathology. Cytokine signals are critical determinants of both protective immunity and immunopathology, and, in this review, we focus on the regulatory cytokine IL‐10 and its role in protozoan and helminth infections. We discuss the sources and targets of IL‐10 during parasite infection, the signals that initiate and reinforce its action, and its impact on the invading parasite, on the host tissue, and on coincident immune responses.
All You Need Is Trust? An Examination of Inter‐organizational Supply Chain Projects
Authors: Brinkhoff Andreas , Özer Özalp , Sargut Gökçe
Published: March 2014

This study examines the antecedents of supply chain project success. We first propose and test a model that describes the role of relationship‐level factors (trust and asymmetric dependence) and project‐level factors (between‐firm communication and within‐firm commitment) in determining supply chain project success. We find that project‐level factors completely mediate the effect of trust on project success. We conclude that trust, despite being a stronger predictor compared to asymmetric dependence, is necessary but not sufficient for supply chain project success. We then proceed to further explore the role of these factors by introducing a categorical scheme that differentiates supply chain projects based on the decision rights configuration of each project. This categorization enables us to explore how relationship‐level and project‐level factors can have different impact on performance based on the characteristics of a supply chain project. The findings offer insights into how to effectively manage supply chain projects and inter‐firm alliances.
Estimating the Impact of Understaffing on Sales and Profitability in Retail Stores
Authors: Mani Vidya , Kesavan Saravanan , Swaminathan Jayashankar M.
Published: March 2014

In this study, we use hourly data on store traffic, sales, and labor from 41 stores of a large retail chain to identify the extent of understaffing in retail stores and quantify its impact on sales and profitability. Using an empirical model motivated from queueing theory, we calculate the benchmark staffing level for each store, and establish the presence of systematic understaffing during peak hours. We find that all 41 stores in our sample are systematically understaffed during a 3‐hour peak period. Eliminating understaffing in these stores can result in a significant increase in sales and profitability in these stores. Also, we examine the extent to which forecasting errors and scheduling constraints drive understaffing in retail stores and quantify their relative impacts on store profits for the retailer in our study.
Use of nitrate non‐utilizing (nit) mutants to determine phenological stages at which Botrytis cinerea infects wine grapes causing botrytis bunch rot
Authors: Hill G. N. , Evans K. J. , Beresford R. M.
Published: March 2014

Botrytis bunch rot (BBR), caused by Botrytis cinerea, degrades wine grapes during ripening, even though infection can occur as early as flowering. Effective BBR management requires knowledge of whether some stages of fruit development are more important than others in relation to infection and BBR severity at harvest. Bunches of Vitis vinifera ‘Sauvignon blanc’ and/or ‘Pinot noir’ were inoculated in two vineyard trials and one glasshouse trial with nitrate non‐utilizing (nit) mutant strains at three phenological stages: early flowering, pre‐bunch closure (PBC) and veraison. Isolates recovered from symptomless berries at veraison and from bunches with symptoms at harvest were screened to measure the incidence of the nit strains used in the inoculations. It was found that latent infections, which resulted in BBR at harvest, could become established at all three phenological stages and no single stage was associated with greater latent incidence or harvest severity than any other stage. It was concluded that a proportion of BBR at harvest resulted from the expression of latent infections that had accumulated throughout the season. However, the time between infection and BBR symptom expression in near‐ripe grape berries was sufficiently short for polycyclic secondary infection to also contribute to epidemic development.
Analysis of the Effects of Communication and Surveillance Facility Service Outages on Traffic Separations
Authors: Borener Sherry S. , Guzhva Vitaly S.
Published: March 2014

This study examines air traffic separations in the service volumes of communication and surveillance facilities that experienced service outages. The data sample consists of 338 unscheduled service outages that happened in 2010 and 2011 at facilities located in the vicinity of 15 major traffic hubs. For each outage, radar track data were collected and used to calculate traffic separations during the period of 30 minutes before to 30 minutes after an outage. Then, the separation index, which indicates the percentage of horizontal separation retained between two aircraft at the same altitude, was estimated. The separation index and loss of separation events were analyzed using lognormal and negative binomial regression models. The results suggest that the count of separation events peaks during the 15 minutes after an outage. In addition, traffic collision avoidance system resolution advisory (TCAS RA) encounters and Category A separation events are 1.31 times more likely during the 30 minutes following the beginning of a service outage, as compared to the 30 minutes before the outage, for both types of facilities. Also, the separation index values are 19% lower following a surveillance facility outage and 4% lower following a communication facility service loss. This study provides evidence that unscheduled service outages of air traffic management facilities are associated with lost or reduced traffic separations and thus can be considered precursors to hazardous loss of separation events.
The AAT1 locus is critical for the biosynthesis of esters contributing to ‘ripe apple’ flavour in ‘Royal Gala’ and ‘Granny Smith’ apples
Authors: Souleyre Edwige J. F. , Chagné David , Chen Xiuyin , Tomes Sumathi , Turner Rebecca M. , Wang Mindy Y. , Maddumage Ratnasiri , Hunt Martin B. , Winz Robert A. , Wiedow Claudia , Hamiaux Cyril , Gardiner Susan E. , Rowan Daryl D. , Atkinson Ross G.
Published: March 2014

The ‘fruity’ attributes of ripe apples (Malus × domestica) arise from our perception of a combination of volatile ester compounds. Phenotypic variability in ester production was investigated using a segregating population from a ‘Royal Gala’ (RG; high ester production) × ‘Granny Smith’ (GS; low ester production) cross, as well as in transgenic RG plants in which expression of the alcohol acyl transferase 1 (AAT1) gene was reduced. In the RG × GS population, 46 quantitative trait loci (QTLs) for the production of esters and alcohols were identified on 15 linkage groups (LGs). The major QTL for 35 individual compounds was positioned on LG2 and co‐located with AAT1. Multiple AAT1 gene variants were identified in RG and GS, but only two (AAT1‐RGa and AAT1‐GSa) were functional. AAT1‐RGa and AAT1‐GSa were both highly expressed in the cortex and skin of ripe fruit, but AAT1 protein was observed mainly in the skin. Transgenic RG specifically reduced in AAT1 expression showed reduced levels of most key esters in ripe fruit. Differences in the ripe fruit aroma could be perceived by sensory analysis. The transgenic lines also showed altered ratios of biosynthetic precursor alcohols and aldehydes, and expression of a number of ester biosynthetic genes increased, presumably in response to the increased substrate pool. These results indicate that the AAT1 locus is critical for the biosynthesis of esters contributing to a ‘ripe apple’ flavour.
The CHH motif in sugar beet satellite DNA: a modulator for cytosine methylation
Authors: Zakrzewski Falk , Schubert Veit , Viehoever Prisca , Minoche André E. , Dohm Juliane C. , Himmelbauer Heinz , Weisshaar Bernd , Schmidt Thomas
Published: March 2014

Methylation of DNA is important for the epigenetic silencing of repetitive DNA in plant genomes. Knowledge about the cytosine methylation status of satellite DNAs, a major class of repetitive DNA, is scarce. One reason for this is that arrays of tandemly arranged sequences are usually collapsed in next‐generation sequencing assemblies. We applied strategies to overcome this limitation and quantified the level of cytosine methylation and its pattern in three satellite families of sugar beet (Beta vulgaris) which differ in their abundance, chromosomal localization and monomer size. We visualized methylation levels along pachytene chromosomes with respect to small satellite loci at maximum resolution using chromosome‐wide fluorescent in situ hybridization complemented with immunostaining and super‐resolution microscopy. Only reduced methylation of many satellite arrays was obtained. To investigate methylation at the nucleotide level we performed bisulfite sequencing of 1569 satellite sequences. We found that the level of methylation of cytosine strongly depends on the sequence context: cytosines in the CHH motif show lower methylation (44–52%), while CG and CHG motifs are more strongly methylated. This affects the overall methylation of satellite sequences because CHH occurs frequently while CG and CHG are rare or even absent in the satellite arrays investigated. Evidently, CHH is the major target for modulation of the cytosine methylation level of adjacent monomers within individual arrays and contributes to their epigenetic function. This strongly indicates that asymmetric cytosine methylation plays a role in the epigenetic modification of satellite repeats in plant genomes.
Do Performance Measures of Donors' Aid Allocation Underperform?
Authors: Clist Paul
Published: March 2014

Indices of donor performance abound. Their recent popularity has occurred within the context of pessimism over aid's impact and optimism over the effect of changes in donor behaviour. Rankings of donor allocative performance aim to change donor behaviour, either through direct pressure on governments or indirectly through public engagement. The indices themselves rely on descriptive measures, and typically claim methodological superiority over positive alternatives due to their simplicity. However, there are two problems. First, measures do not seem robust to simple variations in methodology. Second, correlation amongst competing indices is low, leading to a host of contradictory judgements. This offers neither clear technical guidance nor consistent political pressure. The advantages and disadvantages of the approach are discussed, building upon the more general critique of aggregate indices. I suggest a graphical solution that embraces the advantages of the descriptive approach (including ease of public communication) while avoiding some of its major weaknesses (which typically stem from aggregation).
Aloe vera: an in vitro study of effects on corneal wound closure and collagenase activity
Authors: Curto Elizabeth M. , Labelle Amber , Chandler Heather L.
Published: March 2014

Purpose

To evaluate the in vitro effects of an aloe vera solution on (i) the viability and wound healing response of corneal cells and (ii) the ability to alter collagenase and gelatinase activities.

Methods

Primary cultures of corneal epithelial cells and fibroblasts were prepared from grossly normal enucleated canine globes and treated with an aloe solution (doses ranging from 0.0–2 mg/mL). Cellular viability was evaluated using a colorimetric assay. A corneal wound healing model was used to quantify cellular ingrowth across a defect made on the confluent surface. Anticollagenase and antigelatinase activities were evaluated by incubating a bacterial collagenase/gelatinase with aloe solution (doses ranging from 0.0–500 μg/mL) and comparing outcome measures to a general metalloproteinase inhibitor, 1, 10‐phenanthroline, and canine serum (doses ranging from 0.0–100%).

Results

None of the concentrations of aloe solution tested significantly affected the viability of corneal epithelial cells or fibroblasts. Concentrations ≤175 μg/mL slightly accelerated corneal epithelial cell wound closure; this change was not significant. Concentrations ≥175 μg/mL significantly (P ≤ 0.001) slowed the rate of corneal fibroblast wound closure, while aloe concentrations <175 μg/mL did not significantly alter fibroblast wound closure. Aloe solution did not alter the ability for collagenase to degrade gelatin or collagen Type I but increased the ability for collagenase to degrade Type IV collagen.

Conclusions

Although additional experiments are required, lower concentrations of aloe solution may be beneficial in healing of superficial corneal wounds to help decrease fibrosis and speed epithelialization. An increase in collagenase activity with aloe vera warrants further testing before considering in vivo studies.
It's a gut feeling: How the gut microbiota affects the state of mind
Authors: Farmer Adam D. , Randall Holly A. , Aziz Qasim
Published: March 2014

Common human experience shows that stress and anxiety may modulate gut function. Such observations have been combined with an increasing evidence base that has culminated in the concept of the brain–gut axis. Nevertheless, it has not been until recently that the gut and its attendant components have been considered to influence higher cerebral function and behaviour per se. Moreover, the proposal that the gut and the bacteria contained therein (collectively referred to as the microbiota) can modulate mood and behaviours, has an increasing body of supporting evidence, albeit largely derived from animal studies. The gut microbiota is a dynamic and diverse ecosystem and forms a symbiotic relationship with the host. Herein we describe the components of the gut microbiota and mechanisms by which it can influence neural development, complex behaviours and nociception. Furthermore, we propose the novel concept of a ‘state of gut’ rather than a state of mind, particularly in relation to functional bowel disorders. Finally, we address the exciting possibility that the gut microbiota may offer a novel area of therapeutic intervention across a diverse array of both affective and gastrointestinal disorders.
Physiological underpinnings of irritable bowel syndrome: neurohormonal mechanisms
Authors: Camilleri Michael
Published: March 2014

The gastrointestinal tract is a vast neuroendocrine organ with extensive extrinsic and intrinsic neural circuits that interact to control its function. Circulating and paracrine hormones (amine and peptide) provide further control of secretory, absorptive, barrier, motor and sensory mechanisms that are essential to the digestion and assimilation of nutrients, and the transport and excretion of waste products. Specialized elements of the mucosa (including enteroendocrine cells, enterocytes and immune cells) and the microbiome interact with other intraluminal contents derived from the diet, and with endogenous chemicals that alter the gut's functions. The totality of these control mechanisms is often summarized as the brain–gut axis. In irritable bowel syndrome (IBS), which is the most common gastrointestinal disorder, there may be disturbances at one or more of these diverse control mechanisms. Patients present with abdominal pain in association with altered bowel function. This review documents advances in understanding the pathophysiological mechanisms in the brain–gut axis in patients with IBS. It is anticipated that identification of one or more disordered functions in clinical practice will usher in a renaissance in the management of IBS, leading to effective therapy tailored to the needs of the individual patient.
Water Intake Accelerates Parasympathetic Reactivation After High-Intensity Exercise
Authors: Peçanha Tiago , Paula-Ribeiro Marcelle , Campana-Rezende Edson , Bartels Rhenan , Marins João Carlos Bouzas , de Lima Jorge Roberto Perrout
Published: March 2014

It has been shown that water intake (WI) improves postexercise parasympathetic recovery after moderateintensity exercise session. However, the potential cardiovascular benefit promoted by WI has not been investigated after high-intensity exercise.

Purpose:

To assess the effects of WI on post high-intensity parasympathetic recovery.

Methods:

Twelve recreationally active young men participated in the study (22 ± 1.4 years, 24.1 ± 1.6 kg.m−2). The experimental protocol consisted of two visits to the laboratory. Each visit consisted in the completion of a 30-min high-intensity [~80% of maximal heart rate (HR)] cycle ergometer aerobic session performing randomly the WI or control (CON, no water consumption) intervention at the end of the exercise. HR and RR intervals (RRi) were continuously recorded by a heart rate monitor before, during and after the exercise. Differences in HR recovery [e.g., absolute heart rate decrement after 1 min of recovery (HRR60s) and time-constant of the first order exponential fitting curve of the HRR (HRRτ)] and in postexercise vagalrelated heart rate variability (HRV) indexes (rMSSD30s, rMSSD, pNN50, SD1 and HF) were calculated and compared for WI and CON.

Results:

A similar HR recovery and an increased postexercise HRV [SD1 = 9.4 ± 5.9 vs. 6.0 ± 3.9 millisecond, HF(ln) = 3.6 ± 1.4 vs. 2.4 ± 1.3 millisecond2, for WI and CON, respectively; p < .05] was observed in WI compared with CON.

Conclusion:

The results suggest that WI accelerates the postexercise parasympathetic reactivation after high-intensity exercise. Such outcome reveals an important cardioprotective effect of WI.
Nutritional Recommendations for Synchronized Swimming
Authors: Robertson Sherry , Benardot Dan , Mountjoy Margo
Published: March 2014

The sport of synchronized swimming is unique, because it combines speed, power, and endurance with precise synchronized movements and high-risk acrobatic maneuvers. Athletes must train and compete while spending a great amount of time underwater, upside down, and without the luxury of easily available oxygen. This review assesses the scientific evidence with respect to the physiological demands, energy expenditure, and body composition in these athletes. The role of appropriate energy requirements and guidelines for carbohydrate, protein, fat, and micronutrients for elite synchronized swimmers are reviewed. Because of the aesthetic nature of the sport, which prioritizes leanness, the risks of energy and macronutrient deficiencies are of significant concern. Relative Energy Deficiency in Sport and disordered eating/eating disorders are also of concern for these female athletes. An approach to the healthy management of body composition in synchronized swimming is outlined. Synchronized swimmers should be encouraged to consume a well-balanced diet with sufficient energy to meet demands and to time the intake of carbohydrate, protein, and fat to optimize performance and body composition. Micronutrients of concern for this female athlete population include iron, calcium, and vitamin D. This article reviews the physiological demands of synchronized swimming and makes nutritional recommendations for recovery, training, and competition to help optimize athletic performance and to reduce risks for weight-related medical issues that are of particular concern for elite synchronized swimmers.
Antagonism of EGFR and HER3 Enhances the Response to Inhibitors of the PI3K-Akt Pathway in Triple-Negative Breast Cancer
Authors: Tao Jessica J. , Castel Pau , Radosevic-Robin Nina , Elkabets Moshe , Auricchio Neil , Aceto Nicola , Weitsman Gregory , Barber Paul , Vojnovic Borivoj , Ellis Haley , Morse Natasha , Viola-Villegas Nerissa Therese , Bosch Ana , Juric Dejan , Hazra Saswati , Singh Sharat , Kim Phillip , Bergamaschi Anna , Maheswaran Shyamala , Ng Tony , Penault-Llorca Frédérique , Lewis Jason S. , Carey Lisa A. , Perou Charles M. , Baselga José , Scaltriti Maurizio
Published: March 2014

Predictions regarding drug resistance mechanisms and treatment strategies in triple-negative breast cancer are confirmed in tumors from patients.
Flipping the Switch: Integrin Switching Provides Metastatic Competence
Authors: Madamanchi Aasakiran , Zijlstra Andries , Zutter Mary M.
Published: March 2014

Tumor growth and metastasis is delicately regulated by distinct β integrins.
Focus Issue: Refining the War on Cancer
Authors: Ferrarelli Leslie K.
Published: March 2014

Cancer therapies must not only prevent tumor growth, but also prevent the development of drug resistance and metastases.
Suppressed by B Cells
Authors: Gough Nancy R.
Published: March 2014

A subset of B cells secretes the immunosuppressive cytokine IL-35, which has implications for autoimmune disease and infection.
Evaluation of Ceftaroline, Vancomycin, Daptomycin, or Ceftaroline plus Daptomycin against Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus in an
In Vitro
Pharmacokinetic/Pharmacodynamic Model of Simulated Endocardial Vegetations
Authors: Werth Brian J. , Barber Katie E. , Ireland Cortney E. , Rybak Michael J.
Published: March 2014

Infective endocarditis (IE) caused by methicillin-resistant
Staphylococcus aureus
(MRSA) with reduced susceptibility to vancomycin and daptomycin has few adequate therapeutic options. Ceftaroline (CPT) is bactericidal against daptomycin (DAP)-nonsusceptible (DNS) and vancomycin-intermediate MRSA, but supporting data are limited for IE. This study evaluated the activities of ceftaroline, vancomycin, daptomycin, and the combination of ceftaroline plus daptomycin against DNS MRSA in a pharmacokinetic/pharmacodynamic (PK/PD) model of simulated endocardial vegetations (SEVs). Simulations of ceftaroline-fosamil (600 mg) every 8 h (q8h) (maximum concentration of drug in serum [
C
max
], 21.3 mg/liter; half-life [
t
1/2
], 2.66 h), daptomycin (10 mg/kg of body weight/day) (
C
max
, 129.7 mg/liter;
t
1/2
, 8 h), vancomycin (1 g) q8h (minimum concentration of drug in serum [
C
min
], 20 mg/liter;
t
1/2
, 5 h), and ceftaroline plus daptomycin were evaluated against 3 clinical DNS, vancomycin-intermediate MRSA in a two-compartment,
in vitro
, PK/PD SEV model over 96 h with a starting inoculum of ∼8 log
10
CFU/g. Bactericidal activity was defined as a ≥3-log
10
CFU/g reduction from the starting inoculum. Therapeutic enhancement of combinations was defined as ≥2-log
10
CFU/g reduction over the most active agent alone. MIC values for daptomycin, vancomycin, and ceftaroline were 4 mg/liter, 4 to 8 mg/liter, and 0.5 to 1 mg/liter, respectively, for all strains. At simulated exposures, vancomycin was bacteriostatic, but daptomycin and ceftaroline were bactericidal. By 96 h, ceftaroline monotherapy offered significantly improved killing compared to other agents against one strain. The combination of DAP plus CPT demonstrated therapeutic enhancement, resulting in significantly improved killing versus either agent alone against 2/3 (67%) strains. CPT demonstrated bactericidal activity against DNS, vancomycin-intermediate MRSA at high bacterial densities. Ceftaroline plus daptomycin may offer more rapid and sustained activity against some MRSA in the setting of high-inoculum infections like IE and should also be considered.
Novel Functions of an Iron-Sulfur Flavoprotein from Trichomonas vaginalis Hydrogenosomes
Authors: Smutná Tamara , Pilarová Katerina , Tarábek Ján , Tachezy Jan , Hrdý Ivan
Published: March 2014

Iron-sulfur flavoproteins (Isf) are flavin mononucleotide (FMN)- and FeS cluster-containing proteins commonly encountered in anaerobic prokaryotes. However, with the exception of Isf from
Methanosarcina thermophila
, which participates in oxidative stress management by removing oxygen and hydrogen peroxide, none of these proteins has been characterized in terms of function.
Trichomonas vaginalis
, a sexually transmitted eukaryotic parasite of humans, was found to express several iron-sulfur flavoprotein (TvIsf) homologs in its hydrogenosomes. We show here that in addition to having oxygen-reducing activity, the recombinant TvIsf also functions as a detoxifying reductase of metronidazole and chloramphenicol, both of which are antibiotics effective against a variety of anaerobic microbes. TvIsf can utilize both NADH and reduced ferredoxin as electron donors. Given the prevalence of Isf in anaerobic prokaryotes, we propose that these proteins are central to a novel defense mechanism against xenobiotics.
Simplified Equations Using Two Concentrations To Calculate Area under the Curve for Antimicrobials with Concentration-Dependent Pharmacodynamics: Daptomycin as a Motivating Example
Authors: Pai Manjunath P. , Russo Alessandro , Novelli Andrea , Venditti Mario , Falcone Marco
Published: March 2014

The effects of several antimicrobial agents are predicted by the ratio of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC). Peak (
C
p
) and trough (
C
t
) concentrations are often measured clinically as surrogates of AUC because actual computation of AUC from 1 or 2 samples requires sophisticated mathematical methods. Given that the effects of daptomycin are predicted by AUC/MIC, our objective was to compare simple equation calculated AUC based on
C
p
and
C
t
to model integrated AUC. A standard population pharmacokinetic model was used to simulate 5,000 daptomycin concentration-time profiles after 5 doses of 6 mg/kg of body weight/day (0.5-h infusions). The AUC for the 24-h period was computed by integration and by equations with 110
C
p
-
C
t
combination pairs. The
C
p
time points were in 15-min increments between 0.5 h and 3 h and
C
t
in 15-min increments within an hour of the end of the dosing interval for each dose. The precision and bias of the calculated AUC relative to the integrated AUC were determined to identify
C
p
-
C
t
pairs associated with the lowest bias and highest precision. The equations were further validated using two daptomycin concentration-time data sets from healthy volunteers and critically ill patients. The precision and bias of calculated AUC were based primarily on
C
p
, and use of a daptomycin
C
p
1.5 h to 3 h from the start of infusion was associated with a bias of <10% and an
R
2
of >0.95. Data from the healthy volunteers and critically ill patients also demonstrated declining bias with use of
C
p
≥1.5 h from the start of infusion with relatively good precision. Simplified equations using a daptomycin
C
p
approximately 2 h from the start of infusion and a
C
t
within an hour of the end of the dosing interval should yield precise and unbiased estimates of daptomycin AUC.
Clostridium difficile Extracytoplasmic Function σ Factor σ
V
Regulates Lysozyme Resistance and Is Necessary for Pathogenesis in the Hamster Model of Infection
Authors: Ho Theresa D. , Williams Kyle B. , Chen Yan , Helm Richard F. , Popham David L. , Ellermeier Craig D.
Published: March 2014

Clostridium difficile
is a clinically important pathogen and the most common cause of hospital-acquired infectious diarrhea. Expression of the
C. difficile
gene
csfV
, which encodes σ
V
, an extracytoplasmic function σ factor, is induced by lysozyme, which damages the peptidoglycan of bacteria. Here we show that σ
V
is required for lysozyme resistance in
C. difficile
. Using microarray analysis, we identified the
C. difficile
genes whose expression is dependent upon σ
V
and is induced by lysozyme. Although the peptidoglycan of wild-type
C. difficile
is intrinsically highly deacetylated, we have found that exposure to lysozyme leads to additional peptidoglycan deacetylation. This lysozyme-induced deacetylation is dependent upon σ
V
. Expression of
pdaV
, which encodes a putative peptidoglycan deacetylase, was able to increase lysozyme resistance of a
csfV
mutant. The
csfV
mutant strain is severely attenuated compared to wild-type
C. difficile
in a hamster model of
C. difficile
-associated disease. We conclude that the σ
V
signal transduction system, which senses the host innate immune defense enzyme lysozyme, is required for lysozyme resistance and is necessary during
C. difficile
infection.
Not your typical torticollis: a case of atlantoaxial rotatory subluxation
Authors: Hussain Kosar , Mohamad Abdo Motea , AlNajjar Firas Jaafar Kareem , Abbo Michael
Published: March 2014

A 9-year-old boy was pushed while carrying a heavy backpack. He had no fall or direct trauma to his neck. After a few hours from the incident, he presented with neck pain and torticollis. However, somewhat atypical for torticollis, he was not able to rotate his face to the neutral position. There were no neurological deficits. Concerned by his inability to rotate his neck, the clinician suggested CT of the upper cervical spine, which demonstrated rotary subluxation of the atlantoaxial junction. The patient was taken to the operating theatre. Reduction was performed under general anaesthesia. He did well and was back to school in the following days.
Small cell lung carcinoma presenting as a caecal polyp on surveillance colonoscopy
Authors: Khan Abdullah Mohammad , Khan Sunniya , Dave Vinnidhy , Bhurgri Hadi
Published: March 2014

A 60-year-old man underwent surveillance colonoscopy that demonstrated five subcentimetre polyps, all of which were biopsied. One of the five polyps had histopathology consistent with small cell lung carcinoma (SCLC) metastasis from primary lung cancer. Subsequent imaging demonstrated a spiculated mass in the right upper lung lobe with metastasis to the brain, liver and spleen. He was immediately treated with palliative whole-brain irradiation followed by eight cycles of carboplatin and etoposide. Despite aggressive management, he had disease progression characterised by worsening performance status and development of transfusion-dependent anaemia, new blastic bone lesions and epidural disease. Given his liver failure, he was not considered a candidate for second-line topotecan. After discussion with the patient, family and palliative services, he was discharged with home hospice. This report describes a rare case of advanced SCLC presenting as a metastatic caecal polyp on surveillance colonoscopy.
Kikuchi-Fujimoto’s disease with abdominal pain due to intra-abdominal lymphadenitis
Authors: Noda Ayako , Kenzaka Tsuneaki , Sakatani Takashi , Kajii Eiji
Published: March 2014

A 29-year-old woman was admitted to our hospital with fever and abdominal pain. Abdominal echogram and CT revealed intra-abdominal lymphadenopathy. Seven days after the onset, she developed cervical lymphadenitis. Kikuchi-Fujimoto’s disease (KFD) was diagnosed on cervical lymph node biopsy. Although KFD with intra-abdominal lymphadenopathy is rare, it should be considered in young adults with intra-abdominal lymphadenitis. Because KFD is a benign, self-limiting disease, we suggest the use of a minimally invasive method of diagnosis such as superficial lymph node biopsy.
Cost-effectiveness of enhancing adherence with oral bisphosphonates treatment in osteoporotic women: an empirical approach based on healthcare utilisation databases
Authors: Scotti Lorenza , Arfè Andrea , Zambon Antonella , Merlino Luca , Corrao Giovanni
Published: March 2014

Objective

Adherence with bisphosphonates therapy is generally low. Enhancing adherence with bisphosphonates would be effective in achieving the full benefits of therapy albeit a growth in the expenditure for supporting incremented drug use is expected. The cost-effectiveness of enhancing adherence with oral bisphosphonates in a large population of osteoporotic women has been assessed in the current study.

Design

Retrospective cohort study.

Setting

Healthcare utilisation databases of Lombardy Region, Italy.

Participants

A cohort of 28 558 women aged 45 years or more, resident in the Italian Region of Lombardy, who were newly treated with oral bisphosphonates during 2003–2004, was followed for 6 years after index prescription.

Outcome measures

Fracture-free survival time, healthcare cost and incremental cost-effectiveness ratio (ICER) of enhancing adherence, that is, the additional cost that would be spent every year for gaining one fracture-free year as a consequence of enhancing adherence at a certain level.

Results

Enhanced adherence from 33% (baseline) to 80%, increased both fracture-free survivals from 970 to 973 years and healthcare costs from €118 000 to €265 000 every 1000 woman-years, with ICER value of €53 000 (95% CI €49 000 to €58 000). ICER values were lower for older women (€50 000; 95% CI €42 000 to €58 000) and for those suffering from at least a chronic comorbidity (€25000; 95% CI 95% CI €7000 to €47 000).

Conclusions

Enhancing adherence with oral bisphosphonates offers important benefits in reducing the risk of fracture, although at a substantial cost.
Hydromechanical response of a bedded argillaceous rock formation to excavation and water injection
Authors: Le A.D. , Nguyen T.S.
Published: March 2014

Opalinus clay is a candidate host formation for the geological disposal of nuclear wastes in Switzerland. The understanding of its long-term mechanical (M) and hydraulic (H) behaviour is an essential requirement for the assessment of its performance as a barrier against radionuclide transport. To study the HM response of Opalinus clay, a microtunnel, 13 m in length and 1 m in diameter, was excavated in that formation at the Mont Terri Underground Research Facility. The rock mass was equipped with sensors to measure the deformation and pore pressure in the rock mass during and after the excavation. A mathematical model that couples the equations of flow and mechanical equilibrium was developed to simulate the HM response of the rock mass. An anisotropic plastic constitutive relationship, based on a microstructure tensor approach, was incorporated in the model. Creep was also considered, as well as the anisotropy of permeability. It is shown that the model satisfactorily predicts the shape and extent of the excavation damage zone (EDZ), deformation, and pore pressure in the rock mass. It is also shown that anisotropy and creep play an important role in the HM response of the rock mass to excavation. The model was further used to simulate water injection tests performed at the test section in the microtunnel. The results show that EDZ, due to its high permeability, is a preferential groundwater flow path along the microtunnel.