bluuebunny/crossref_metadata_2025 huggingface dataset:
USE OF THE T2*‐WEIGHTED GRADIENT RECALLED ECHO SEQUENCE FOR MAGNETIC RESONANCE IMAGING OF THE CANINE AND FELINE BRAIN
Authors: Hodshon Amy W. , Hecht Silke , Thomas William B.
Published: May 2014

T2*‐weighted magnetic resonance imaging (MRI) has been reported to help improve detection of intracranial hemorrhage and is widely used in human neuroimaging. To assess the utility of this technique in small animals, interpretations based on this sequence were compared with those based on paired T2‐weighted and fluid‐attenuated inversion recovery (FLAIR) sequences in 200 dogs and cats that underwent brain MRI for suspected intracranial disease. Two sets of images (T2 + FLAIR and T2*) were reviewed separately in random order unaccompanied by patient information and were interpreted as normal or abnormal based on whether intracranial abnormalities were seen. The number and location of intracranial lesions were recorded. Eighty‐five studies were considered normal and 88 were considered abnormal based on both sets of images, with good agreement (κ = 0.731) between the two. Susceptibility artifact was present in 33 cases (16.5%) on T2*‐weighted images. In 12 cases (6%) a total of 69 lesions were seen on T2*‐weighted images that were not seen on T2/FLAIR, all of which were associated with susceptibility artifact caused by presumed intracranial hemorrhage. Pseudolesions were seen on T2*‐weighted images in five cases, none of which were associated with susceptibility artifact. Abnormalities were seen on T2/FLAIR images that were not seen on T2*‐weighted images in 35 cases, confirming that T2* does not replace standard spin echo sequences. These results support inclusion of T2*‐weighted sequences in small animal brain MRI studies and indicate that that a large number of abnormalities (especially hemorrhagic lesions) can go undetected if it is not performed.
COMPUTED TOMOGRAPHIC IDENTIFICATION OF DYSPLASIA AND PROGRESSION OF OSTEOARTHRITIS IN DOG ELBOWS PREVIOUSLY ASSIGNED OFA GRADES 0 AND 1
Authors: Kunst Chelsea M. , Pease Anthony P. , Nelson Nathan C. , Habing Greg , Ballegeer Elizabeth A.
Published: May 2014

Elbow dysplasia is a heritable disease that is a common cause of lameness and progressive elbow osteoarthritis in young large breed dogs. The Orthopedic Foundation for Animals (OFA) screens elbow radiographs, and assigns grades 0–3 based on presence and severity of bony proliferation on the anconeal process. Grade 1 is assigned when less than 3 mm is present and considered positive for dysplasia. We investigated the incidence of elbow dysplasia and progression of osteoarthritis in elbows with grades 0 and 1 in 46 elbows screened at least 1 year previously, using CT as a gold standard and with the addition of CT absorptiometry. The incidence of dysplasia based on CT was 62% in grade 0, and 75% in grade 1 elbows, all of which had medial coronoid disease. Progressive osteoarthritis at recheck was consistent with elbow dysplasia. The sensitivity and specificity of the OFA grade for elbow dysplasia compared to CT findings was 75% and 38%, respectively. Increased bone mineral density of the medial coronoid process as characterized by osteoabsorptiometry warrants further investigation with respect to elbow dysplasia. Proliferation on the anconeal process without CT evidence of dysplasia or osteoarthritis was present in 20% of the elbows, and is theorized to be an anatomic variant or enthesopathy of the olecranon ligament/synovium. Results of our study suggest that the “anconeal bump” used for elbow screening by the OFA is a relatively insensitive characteristic, and support the use of CT for identifying additional characteristics of elbow dysplasia.
A PROPOSED RADIOGRAPHIC CLASSIFICATION SCHEME FOR CONGENITAL THORACIC VERTEBRAL MALFORMATIONS IN BRACHYCEPHALIC “SCREW‐TAILED” DOG BREEDS
Authors: Gutierrez‐Quintana Rodrigo , Guevar Julien , Stalin Catherine , Faller Kiterie , Yeamans Carmen , Penderis Jacques
Published: May 2014

Congenital vertebral malformations are common in brachycephalic “screw‐tailed” dog breeds such as French bulldogs, English bulldogs, Boston terriers, and pugs. The aim of this retrospective study was to determine whether a radiographic classification scheme developed for use in humans would be feasible for use in these dog breeds. Inclusion criteria were hospital admission between September 2009 and April 2013, neurologic examination findings available, diagnostic quality lateral and ventro‐dorsal digital radiographs of the thoracic vertebral column, and at least one congenital vertebral malformation. Radiographs were retrieved and interpreted by two observers who were unaware of neurologic status. Vertebral malformations were classified based on a classification scheme modified from a previous human study and a consensus of both observers. Twenty‐eight dogs met inclusion criteria (12 with neurologic deficits, 16 with no neurologic deficits). Congenital vertebral malformations affected 85/362 (23.5%) of thoracic vertebrae. Vertebral body formation defects were the most common (butterfly vertebrae 6.6%, ventral wedge‐shaped vertebrae 5.5%, dorsal hemivertebrae 0.8%, and dorso‐lateral hemivertebrae 0.5%). No lateral hemivertebrae or lateral wedge‐shaped vertebrae were identified. The T7 vertebra was the most commonly affected (11/28 dogs), followed by T8 (8/28 dogs) and T12 (8/28 dogs). The number and type of vertebral malformations differed between groups (P= 0.01). Based on MRI, dorsal, and dorso‐lateral hemivertebrae were the cause of spinal cord compression in 5/12 (41.6%) of dogs with neurologic deficits. Findings indicated that a modified human radiographic classification system of vertebral malformations is feasible for use in future studies of brachycephalic “screw‐tailed” dogs.
International Solidarity or Renewed Trade Union Imperialism? The AFL–CIO and Garment Workers in Bangladesh
Authors: Rahman Zia , Langford Tom
Published: May 2014

This article assesses the AFL–CIO's in Bangladesh's readymade garment (RMG) industry over the past two decades, drawing upon documentary sources and in‐depth interviews conducted in 2007. Our research indicates that AFL–CIO actions clearly match four of the five characteristics of hegemonic trade union imperialism, including initiating its own organizations that it can directly control instead of working with existing unions; and employing bureaucratic and legalistic methods when pursuing workplace grievances. Nevertheless, while we characterize the AFL–CIO's actions in Bangladesh as renewed trade union imperialism, this thrust has been tempered with reformist achievements. These include path‐breaking attention to the development of women workers' leadership skills. We conclude that the labor movement in the RMG industry in Bangladesh will have to find ways to accumulate new resources and credibility and to overcome its historical subservience to the two major Bangladeshi political parties if it is to effectively counter the AFL–CIO's trade union imperialism.
Workers Confront Apartheid: Comparing Canadian Labor Solidarity Campaigns against South African and Israeli Apartheid
Authors: Nastovski Katherine
Published: May 2014

This article explores the challenges of building international labor solidarity by comparing two campaigns that developed inside the Canadian labor movement. I critically compare and assess the campaign against South African apartheid in the 1980s and the more recent efforts to oppose Israeli apartheid. Both campaigns are examples of grassroots international labor solidarity, where organizers sought to build international solidarity through member mobilization and a focus on the power of workers to engage in solidarity actions. I examine how these union activists organized within their unions, and how their organizational differences and the ideological and political contexts they organized within shaped their successes and limitations. Drawing from the work of Antonio Gramsci, I argue that these campaigns were sites of counter‐hegemonic practice both because of the analysis and critiques they offered but also because of the nature of their organizing.
On the continuity of multivariate Lagrange interpolation at natural lattices
Authors: Calvi J.-P. , Phung V. M.
Published: May 2014

We give a natural geometric condition that ensures that sequences of interpolation polynomials (of fixed degree) of sufficiently differentiable functions with respect to the natural lattices introduced by Chung and Yao converge to a Taylor polynomial.
Dehydration affects cerebral blood flow but not its metabolic rate for oxygen during maximal exercise in trained humans
Authors: Trangmar Steven J. , Chiesa Scott T. , Stock Christopher G. , Kalsi Kameljit K. , Secher Niels H. , González‐Alonso José
Published: May 2014

Key points

Dehydration accrued during exercise in the heat challenges systemic and locomotor muscle blood flow, but its impact on cerebral blood flow (CBF) and metabolism remains unknown.

This study assessed whether dehydration compromises CBF and the cerebral metabolic rate for oxygen (CMRO2) during incremental exercise to exhaustion in trained males.

Dehydration induced an early reduction in CBF during progressive exercise, but increased O2 extraction secured CMRO2.

In all hydration conditions declining CBF at high exercise intensities was correlated to decreasing arterial carbon dioxide tension and increasing jugular venous plasma noradrenaline.

These results suggest that dehydration impairs CBF at high exercise intensities, but this circulatory strain on the human brain does not compromise CMRO2.

Intense exercise is associated with a reduction in cerebral blood flow (CBF), but regulation of CBF during strenuous exercise in the heat with dehydration is unclear. We assessed internal (ICA) and common carotid artery (CCA) haemodynamics (indicative of CBF and extra‐cranial blood flow), middle cerebral artery velocity (MCA Vmean), arterial–venous differences and blood temperature in 10 trained males during incremental cycling to exhaustion in the heat (35°C) in control, dehydrated and rehydrated states. Dehydration reduced body mass (75.8 ± 3 vs. 78.2 ± 3 kg), increased internal temperature (38.3 ± 0.1 vs. 36.8 ± 0.1°C), impaired exercise capacity (269 ± 11 vs. 336 ± 14 W), and lowered ICA and MCA Vmean by 12–23% without compromising CCA blood flow. During euhydrated incremental exercise on a separate day, however, exercise capacity and ICA, MCA Vmean and CCA dynamics were preserved. The fast decline in cerebral perfusion with dehydration was accompanied by increased O2 extraction (P < 0.05), resulting in a maintained cerebral metabolic rate for oxygen (CMRO2). In all conditions, reductions in ICA and MCA Vmean were associated with declining cerebral vascular conductance, increasing jugular venous noradrenaline, and falling arterial carbon dioxide tension () (R2 ≥ 0.41, P ≤ 0.01) whereas CCA flow and conductance were related to elevated blood temperature. In conclusion, dehydration accelerated the decline in CBF by decreasing and enhancing vasoconstrictor activity. However, the circulatory strain on the human brain during maximal exercise does not compromise CMRO2 because of compensatory increases in O2 extraction.
Effects of Yogic Practice on Metabolism and Antioxidant–Redox Status of Physically Active Males
Authors: Pal Rameswar , Singh Som Nath , Halder Kaushik , Tomer Omveer Singh , Mishra Awadh Bihari , Saha Mantu
Published: May 2014

Background:

This study was conducted to evaluate the effects of yogic practice on resting metabolism and redox status.

Methods:

The study was conducted on 64 physically trained male volunteers selected randomly at the Air Force Academy. The yoga group (n = 34) practiced yogasana, pranayama, and meditation for 3 months (February–May 2011) and the control group (n = 30) performed physical training. Antioxidant variables in blood samples along with physiological parameters were estimated before and after 3 months.

Results:

No significant difference was noted between baseline data of the control group and yoga group. Reduced glutathione, vitamin C, and vitamin E; the ratio of reduced to oxidized glutathione; and total antioxidant status were increased significantly following yogic practice. Activities of superoxide dismutase, glutathione S-transferase, and glutathione reductase were significantly increased, whereas activity of glutathione peroxidase was significantly decreased following yogic practice. Oxidized glutathione decreased significantly following yogic practice. A nonsignificant decrease of hydroperoxides, protein carbonyl, malondialdehyde, and blood sugar was noted in the yoga group. Carbon dioxide elimination and peripheral oxygen saturation increased significantly following yogic practice. No significant changes were observed in the control group following 3 months of physical training.

Conclusions:

Regular yogic practice can improve resting metabolism and redox status of the practitioner.
Does Age Modify the Cost-Effectiveness of Community-Based Physical Activity Interventions?
Authors: Roux Larissa , Pratt Mike , Lee I-Min , Bazzarre Terry , Buchner David
Published: May 2014

Background:

Community-based efforts to promote physical activity (PA) in adults have been found to be cost-effective in general, but it is unknown if this is true in middle-age specifically. Age group-specific economic evaluations could help inform the design and delivery of better and more tailored PA promotion.

Methods:

A Markov model was developed to estimate the cost-effectiveness (CE) of 7 exemplar community-level interventions to promote PA recommended by the Guide to Community Preventive Services, over a 20-year horizon. The CE of these interventions in 25- to 64-year-old adults was compared with their CE in middle-aged adults, aged 50 to 64 years. The robustness of the results was examined through sensitivity analyses.

Results:

Cost/QALY (quality-adjusted life year) of the evaluated interventions in 25- to 64-year-olds ranged from $42,456/QALY to $145,868/QALY. Interventions were more cost-effective in middle-aged adults, with CE ratios 38% to 47% lower than in 25- to 64-year-old adults. Sensitivity analyses showed greater than a 90% probability that the true CE of 4 of the 7 interventions was below $125,000/QALY in adults aged 50 to 64 years.

Conclusion:

The exemplar PA promotion interventions evaluated appeared to be especially cost-effective for middle-aged adults. Prioritizing such efforts to this age group is a good use of societal resources.
Qualified Fitness and Exercise as Professionals and Exercise Prescription: Evolution of the PAR-Q and Canadian Aerobic Fitness Test
Authors: Shephard Roy J.
Published: May 2014

Background:

Traditional approaches to exercise prescription have included a preliminary medical screening followed by exercise tests of varying sophistication. To maximize population involvement, qualified fitness and exercise professionals (QFEPs) have used a self-administered screening questionnaire (the Physical Activity Readiness Questionnaire, PAR-Q) and a simple measure of aerobic performance (the Canadian Aerobic Fitness Test, CAFT). However, problems have arisen in applying the original protocol to those with chronic disease. Recent developments have addressed these issues.

Methods:

Evolution of the PAR-Q and CAFT protocol is reviewed from their origins in 1974 to the current electronic decision tree model of exercise screening and prescription.

Results:

About a fifth of apparently healthy adults responded positively to the original PAR-Q instrument, thus requiring an often unwarranted referral to a physician. Minor changes of wording did not overcome this problem. However, a consensus process has now developed an electronic decision tree for stratification of exercise risk not only for healthy individuals, but also for those with various types of chronic disease.

Conclusions:

The new approach to clearance greatly reduces physician referrals and extends the role of QFEPs. The availability of effective screening and simple fitness testing should contribute to the goal of maximizing physical activity in the entire population.
Draft Genome Sequences of Six Ruminant Coxiella burnetii Isolates of European Origin
Authors: Sidi-Boumedine Karim , Ellis Richard J. , Adam Gilbert , Prigent Myriam , Angen Øystein , Aspán Anna , Thiéry Richard , Rousset Elodie
Published: May 2014

Coxiella burnetii
is responsible for Q fever, a worldwide zoonosis attributed to the inhalation of aerosols contaminated by livestock birth products. Six draft genome sequences of European
C. burnetii
isolates from ruminants are presented here. The availability of these genomes will help in understanding the potential host specificity and pathogenicity and in identifying pertinent markers for surveillance and tracing.
Draft Genome Sequence of Pseudomonas aeruginosa Strain RB, a Bacterium Capable of Synthesizing Cadmium Selenide Nanoparticles
Authors: Ayano Hiroyuki , Kuroda Masashi , Soda Satoshi , Ike Michihiko
Published: May 2014

Pseudomonas aeruginosa
strain RB is a bacterium capable of synthesizing cadmium selenide (CdSe) nanoparticles and was isolated from a soil sample. Here, we present the draft genome sequence of
P. aeruginosa
strain RB. To the best of our knowledge, this is the first report of a draft genome of a CdSe-synthesizing bacterium.
Complete Genome Sequence of Bovine Pestivirus Strain PG-2, a Second Member of the Tentative Pestivirus Species Giraffe
Authors: Becher Paul , Fischer Nicole , Grundhoff Adam , Stalder Hanspeter , Schweizer Matthias , Postel Alexander
Published: May 2014

We report the complete genome sequence of bovine pestivirus strain PG-2. The sequence data from this virus showed that PG-2 is closely related to the giraffe pestivirus strain H138. PG-2 and H138 belong to one pestivirus species that should be considered an approved member of the genus
Pestivirus.
Metagenomes from the Saline Desert of Kutch
Authors: Pandit A. S. , Joshi M. N. , Bhargava P. , Ayachit G. N. , Shaikh I. M. , Saiyed Z. M. , Saxena A. K. , Bagatharia S. B.
Published: May 2014

We provide the first report on the metagenomic approach for unveiling the microbial diversity in the saline desert of Kutch. High-throughput metagenomic sequencing of environmental DNA isolated from soil collected from seven locations in Kutch was performed on an Ion Torrent platform.
Orthodontic and surgical perspectives in management of a severe skeletal open bite
Authors: Vadgaonkar Vaishali , Gangurde Parag , Deshmukh Vijay , Shah Alok
Published: May 2014

In orthognathic correction of skeletal discrepancy, different treatment options should be considered to give optimum results to the patient with minimal postoperative problems caused by extensive bi-jaw surgery. In a case of severe vertical dysplasia with a large open bite, the orthodontist with the help of advanced diagnostic tools such as imaging software had planned bi-jaw surgery. However, there was a difference in opinion with the oral surgeon who considered only single jaw surgery to get adequate results. The possibility of only maxillary Le Fort I surgery creating autorotation of the mandible was considered, as 0.5° of autorotation results with 1° of maxillary posterior segment clockwise rotation thus avoiding bi-jaw surgery. After performing the Le Fort I superior repositioning of maxilla, the mandibular autorotation was not adequate, so a mandibular bilateral sagittal split osteotomy (BSSO) for mandibular advancement had to be performed to achieve favourable results.
Establishing a person-centred framework of self-identity after traumatic brain injury: a grounded theory study to inform measure development
Authors: Levack William M M , Boland Pauline , Taylor William J , Siegert Richard J , Kayes Nicola M , Fadyl Joanna K , McPherson Kathryn M
Published: May 2014

Objective

To develop a theoretically sound, client-derived framework to underpin development of a measure reflecting the impact of traumatic brain injury (TBI) on a person's self-identity.

Design

Grounded theory, based on transcription of audio recordings from focus group meetings with people who have experienced TBI, analysed with constant comparative methods.

Setting

8 different urban and rural communities in New Zealand.

Participants

49 people (34 men, 15 women), 6 months to 36 years after mild-to-severe TBI.

Results

The central concept emerging from the data was that of desiring to be or having lost a sense of being an integrated and valued person. The three main subthemes were: (1) having a coherent, satisfying and complete sense of oneself, (2) respect, validation and acceptance by others and (3) having a valued place in the world.

Conclusions

This study reinforces the notion that change in self-identity is an important aspect of life after TBI, and provides information on what this concept means to people with TBI. In order to scientifically evaluate relationships between self-identity and other aspects of health (eg, depression, quality of life), and to test the effect of interventions to address problems with self-identity after TBI, a quantitative tool for evaluation of this construct is required. Themes from this research provide a foundation for the development of a measure of self-identity grounded in the language and experience of people with TBI.
Safety of 8-aminoquinolines given to people with G6PD deficiency: protocol for systematic review of prospective studies
Authors: Uthman Olalekan A , Saunders Rachel , Sinclair David , Graves Patricia , Gelband Hellen , Clarke Aileen , Garner Paul
Published: May 2014

Introduction

A single dose or short course of primaquine given to people infected with malaria may reduce transmission ofPlasmodium falciparumthrough its effects on gametocytes. Primaquine is also known to cause haemolysis in people with variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency. The objective of this systematic review was to assess the risk of adverse effects in people with G6PD deficiency given primaquine or other 8-aminoquinoline (8AQ) as a single dose or short course (less than 7 days).

Methods and analysis

We will search the following databases: Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS. Prospective cohort studies, randomised and quasi-randomised trials that evaluated 8AQs for whatever reason in adults or children with a known G6PD deficiency will be included. Two authors will independently assess each study for eligibility, risk of bias and extract data.

Ethics and dissemination

This systematic review will be published in a peer-reviewed journal. Brief reports of the review findings will be disseminated directly to the appropriate audiences and the WHO Technical Expert Group in Malaria Chemotherapy. As no primary data collection will be undertaken, no additional formal ethical assessment and informed consent are required.

Protocol registration in PROSPERO

The protocol is registered with PROSPERO, registration number CRD42013006518.
A UK survey of rehabilitation following critical illness: implementation of NICE Clinical Guidance 83 (CG83) following hospital discharge
Authors: Connolly Bronwen , Douiri A , Steier J , Moxham J , Denehy L , Hart N
Published: May 2014

Objective

To determine the implementation of National Institute for Health and Care Excellence guidance (NICE CG83) for posthospital discharge critical illness follow-up and rehabilitation programmes.

Design

Closed-question postal survey.

Setting

Adult intensive care units (ICUs) across the UK, identified from national databases of organisations. Specialist-only and private ICUs were not included.

Participants

Senior respiratory critical care physiotherapy clinicians.

Results

A representative sample of 182 surveys was returned from the 240 distributed (75.8% (95% CI 70.4 to 81.2)). Only 48 organisations (27.3% (95% CI 20.7 to 33.9)) offered a follow-up service 2–3 months following hospital discharge, the majority (n=39, 84.8%) in clinic format. 12 organisations reported posthospital discharge rehabilitation programmes (6.8% (95% CI 3.1 to 10.5)), albeit only 10 of these operated on a regular basis. Lack of funding was reported as the most frequent (n=149/164, 90%) and main barrier (n=99/156, 63.5%) to providing services. Insufficient resources (n=71/164, 43.3%) and lack of priority by the clinical management team (n=66/164, 40.2%) were also highly cited barriers to service delivery.

Conclusions

NICE CG83 has been successful in profiling the importance of rehabilitation for survivors of critical illness. However, 4 years following publication of CG83 there has been limited development of this clinical service across the UK. Strategies to support delivery of such quality improvement programmes are urgently required to enhance patient care.
The effect of information about overdetection of breast cancer on women's decision-making about mammography screening: study protocol for a randomised controlled trial
Authors: Hersch Jolyn , Barratt Alexandra , Jansen Jesse , Houssami Nehmat , Irwig Les , Jacklyn Gemma , Dhillon Haryana , Thornton Hazel , McGeechan Kevin , Howard Kirsten , McCaffery Kirsten
Published: May 2014

Introduction

Women are largely unaware that mammography screening can cause overdetection of inconsequential disease, leading to overdiagnosis and overtreatment of breast cancer. Evidence is lacking about how information on overdetection affects women's breast screening decisions and experiences. This study investigates the consequences of providing information about overdetection of breast cancer to women approaching the age of invitation to mammography screening.

Methods and analysis

This is a randomised controlled trial with an embedded longitudinal qualitative substudy. Participants are a community sample of women aged 48–50 in New South Wales, Australia, recruited in 2014. Women are randomly allocated to either quantitative only follow-up (n=904) or additional qualitative follow-up (n=66). Women in each stream are then randomised to receive either the intervention (evidence-based information booklet including overdetection, breast cancer mortality reduction and false positives) or a control information booklet (including mortality reduction and false positives only). The primary outcome is informed choice about breast screening (adequate knowledge, and consistency between attitudes and intentions) assessed via telephone interview at 2 weeks postintervention. Secondary outcomes measured at this time include decision process (decisional conflict and confidence) and psychosocial outcomes (anticipated regret, anxiety, breast cancer worry and perceived risk). Women are further followed up at 6 months, 1 and 2 years to assess self-reported screening behaviour and long-term psychosocial outcomes (decision regret, quality of life). Participants in the qualitative stream undergo additional in-depth interviews at each time point to explore the views and experiences of women who do and do not choose to have screening.

Ethics and dissemination

The study has ethical approval, and results will be published in peer-reviewed journals. This research will help ensure that information about overdetection may be communicated clearly and effectively, using an evidence-based approach, to women considering breast cancer screening.

Trial registration number

Australian New Zealand Clinical Trials Registry ACTRN12613001035718.
Coronary artery bypass graft: why is the saphenous vein prone to intimal hyperplasia?
Authors: Sur Swastika , Sugimoto Jeffrey T. , Agrawal Devendra K.
Published: May 2014

Proliferation and migration of smooth muscle cells and the resultant intimal hyperplasia cause coronary artery bypass graft failure. Both internal mammary artery and saphenous vein are the most commonly used bypass conduits. Although an internal mammary artery graft is immune to restenosis, a saphenous vein graft is prone to develop restenosis. We found significantly higher activity of phosphatase and tensin homolog (PTEN) in the smooth muscle cells of the internal mammary artery than in the saphenous vein. In this article, we critically review the pathophysiology of vein-graft failure with detailed discussion of the involvement of various factors, including PTEN, matrix metalloproteinases, and tissue inhibitor of metalloproteinases, in uncontrolled proliferation and migration of smooth muscle cells towards the lumen, and invasion of the graft conduit. We identified potential target sites that could be useful in preventing and (or) reversing unwanted consequences following coronary artery bypass graft using saphenous vein.
MODELING THE SPREAD OF STREET KIDS IN ZIMBABWE
Authors: BHUNU C. P.
Published: May 2014

Child neglect and abuse has been linked with the growth in the number of street kids for some time. A mathematical model is used to explore the impact of peer influence and child abuse in the presence of removal of street kids from the streets into children's homes/foster homes and improvement in the welfare of adults. The threshold quantity known as the reproduction number and equilibria for the model are determined and analyzed. Results from this study suggest that removal of street kids from the streets into children's homes/foster homes and improving the welfare of adults have the potential to reduce the number of children living in the streets. Interestingly, our results illustrate that adult peer influence leading to child abuse of children makes the problem of street kids worse than any other factor. To effectively control the growth in the number of street kids require strategies that address both economic and social factors affecting children and their guardians. Addressing only an issue affecting one group like guardians through improvement of their welfare may not be enough to stem the growth in the number of street kids as some would be turning to the streets due to negative peer influence among children.
LOCAL SEARCH, EXPLORATION FREQUENCY, AND EXPLORATION VALUABLENESS: EVIDENCE FROM NEW PHARMACEUTICALS DEVELOPMENT
Authors: SUZUKI OSAMU , METHÉ DAVID T.
Published: May 2014

Informed by recent theoretical developments concerning absorptive capacity and cognitive representations, we argue that local search positively influences subsequent performance in exploratory innovation. Our empirical analyses of a unique data set on new pharmaceutical development frequency, as well as on official assessments of these pharmaceuticals' valuableness support our argument by showing that knowledge gained as a result of local search increases subsequent performance in exploratory innovation both in terms of its frequency and valuableness. Specifically, local search is shown to be positively associated with the frequency of subsequent exploratory new pharmaceutical developments. We also show that local search is curvilinearly (inverted U-shape) associated with the degree of valuableness of subsequent exploratory new pharmaceuticals. Our empirical findings contribute to the theory of organisational learning and innovation by extending the theory of local search through uncovering more nuanced relationships between local search and subsequent exploratory innovation than those identified by prior works.
Measuring hydraulic conductivity and swelling pressure under high hydraulic gradients
Authors: Hausmannova Lucie , Vasicek Radek
Published: May 2014

The concept of a deep geological repository for high-level waste in the Czech Republic is based on disposal in a granite environment. The construction of an engineered barrier between the rock and canister is considered, and compacted swelling clay (bentonite) is chosen as the most suitable material for such a barrier. The most important geotechnical properties of bentonite in this context are low hydraulic conductivity and high swelling pressure. Measuring these parameters in such a low-permeable material requires much time. This study focuses on combined measurements of hydraulic conductivity and swelling pressure and on the impact of using high hydraulic gradients that are consistent with possible porewater pressures in a deep repository. High hydraulic gradients may also quicken the determination of these parameters. Results show a decrease in hydraulic conductivity with increasing saturation pressure up to a threshold dry density, with no further change at higher dry densities. The influence of saturation pressure on measured pressure decreases with dry density until a certain value is reached. For samples with lower density, the slope of the increase is close to unity.
Interstitial cells of Cajal mediate nitrergic inhibitory neurotransmission in the murine gastrointestinal tract
Authors: Lies Barbara , Gil Víctor , Groneberg Dieter , Seidler Barbara , Saur Dieter , Wischmeyer Erhard , Jiménez Marcel , Friebe Andreas
Published: May 2014

Nitric oxide (NO) is a major inhibitory neurotransmitter in the gastrointestinal (GI) tract. Its main effector, NO-sensitive guanylyl cyclase (NO-GC), is expressed in several GI cell types, including smooth muscle cells (SMC), interstitial cells of Cajal (ICC), and fibroblast-like cells. Up to date, the interplay between neurons and these cells to initiate a nitrergic inhibitory junction potential (IJP) is unclear. Here, we investigate the origin of the nitrergic IJP in murine fundus and colon. IJPs were determined in fundus and colon SMC of mice lacking NO-GC globally (GCKO) and specifically in SMC (SM-GCKO), ICC (ICC-GCKO), and both SMC/ICC (SM/ICC-GCKO). Nitrergic IJP was abolished in ICC-GCKO fundus and reduced in SM-GCKO fundus. In the colon, the amplitude of nitrergic IJP was reduced in ICC-GCKO, whereas nitrergic IJP in SM-GCKO was reduced in duration. These results were corroborated by loss of the nitrergic IJP in global GCKO. In conclusion, our results prove the obligatory role of NO-GC in ICC for the initiation of an IJP. NO-GC in SMC appears to enhance the nitrergic IJP, resulting in a stronger and prolonged hyperpolarization in fundus and colon SMC, respectively. Thus NO-GC in both cell types is mandatory to induce a full nitrergic IJP. Our data from the colon clearly reveal the nitrergic IJP to be biphasic, resulting from individual inputs of ICC and SMC.
The effects of PGC-1α on control of microvascular Po2kinetics following onset of muscle contractions
Authors: Kano Yutaka , Miura Shinji , Eshima Hiroaki , Ezaki Osamu , Poole David C.
Published: May 2014

During contractions, regulation of microvascular oxygen partial pressure (Pmvo2), which drives blood-myocyte O2flux, is a function of skeletal muscle fiber type and oxidative capacity and can be altered by exercise training. The kinetics of Pmvo2during contractions in predominantly fast-twitch muscles evinces a more rapid fall to far lower levels compared with slow-twitch counterparts. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) improves endurance performance, in part, due to mitochondrial biogenesis, a fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. We tested the hypothesis that improvement of exercise capacity by genetic overexpression of PGC-1α would be associated with an altered Pmvo2kinetics profile of the fast-twitch (white) gastrocnemius during contractions toward that seen in slow-twitch muscles (i.e., slowed response kinetics and elevated steady-state Pmvo2). Phosphorescence quenching techniques were used to measure Pmvo2at rest and during separate bouts of twitch (1 Hz) and tetanic (100 Hz) contractions in gastrocnemius muscles of mice with overexpression of PGC-1α and wild-type littermates (WT) mice under isoflurane anesthesia. Muscles of PGC-1α mice exhibited less fatigue than WT ( P < 0.01). However, except for the Pmvo2response immediately following onset of contractions, WT and PGC-1α mice demonstrated similar Pmvo2kinetics. Specifically, the time delay of the Pmvo2response was shortened in PGC-1α mice compared with WT (1 Hz: WT, 6.6 ± 2.4 s; PGC-1α, 2.9 ± 0.8 s; 100 Hz: WT, 3.3 ± 1.1 s, PGC-1α, 0.9 ± 0.3 s, both P < 0.05). The ratio of muscle force to Pmvo2was higher for the duration of tetanic contractions in PGC-1α mice. Slower dynamics and maintenance of higher Pmvo2following muscle contractions is not obligatory for improved fatigue resistance in fast-twitch muscle of PGC-1α mice. Moreover, overexpression of PGC-1α may accelerate O2utilization kinetics to a greater extent than O2delivery kinetics.
Neutrophils release extracellular DNA traps in response to exercise
Authors: Beiter Thomas , Fragasso Annunziata , Hudemann Jens , Schild Marius , Steinacker Jürgen , Mooren Frank C. , Niess Andreas M.
Published: May 2014

Intense exercise evokes a rapid and transient increase in circulating cell-free DNA (cf-DNA), a phenomenon that is commonly observed in a variety of acute and chronic inflammatory conditions. In this study, we aimed to shed new light on the release and clearance mechanisms of cf-DNA in response to exercise. We hypothesized that activated neutrophils may primarily contribute to exercise-evoked cf-DNA levels by releasing neutrophil extracellular traps (NETs). Analysis of plasma and/or serum samples from male athletes at rest and in response to exhaustive treadmill exercise revealed an immediate and transient increase in cf-DNA that was concomitantly counterbalanced by an increase in serum DNase activity. Consistently, rapid release and clearance kinetics for cf-DNA could also be observed in response to intensive cycling exercise, with no significant differences between endurance-trained (V̇o2max>57 ml·min−1·kg−1) and healthy (V̇o2max<49 ml·min−1·kg−1) sedentary individuals. In postexercise blood smear samples, we detected seemingly intact neutrophils displaying morphological signs of NET release, as indicated by abnormal swollen nuclei and emanating DNA fibers. In support, we observed a striking correlation of postexercise cf-DNA concentrations with plasma levels of the granule-derived enzyme myeloperoxidase. Our study indicates that intense exercise induces liberation of NETs, which is sufficiently counterbalanced in healthy individuals by a concomitant rise in serum DNase activity. As aberrant release of NETs has been linked to diverse disease states, monitoring of cf-DNA/DNase levels or activities in response to standardized exercise testing could provide a valuable tool to identify people who are at increased risk for cardiac ischemia, thrombosis, autoimmunity, or chronic fatigue.
Activating cAMP/PKA signaling in skeletal muscle suppresses the ubiquitin-proteasome-dependent proteolysis: implications for sympathetic regulation
Authors: Silveira W. A. , Gonçalves D. A. , Graça F. A. , Andrade-Lopes A. L. , Bergantin L. B. , Zanon N. M. , Godinho R. O. , Kettelhut I. C. , Navegantes L. C. C.
Published: May 2014

Although we have recently demonstrated that plasma catecholamines induce antiproteolytic effects on skeletal muscle (Graça FA, Gonçalves DAP, Silveira WA, Lira EC, Chaves VE, Zanon NM, Garófalo MAR, Kettelhut IC, Navegantes LCC. Am J Physiol Endocrinol Metab. 305: E1483-E1494, 2013), the role of the muscle sympathetic innervation and, more specifically, norepinephrine (NE) in regulating the ubiquitin (Ub)-proteasome system (UPS) remains unknown. Based on previous findings that chemical sympathectomy acutely reduces UPS activity, we hypothesized that muscle NE depletion induces adrenergic supersensitivity in rat skeletal muscles. We report that surgical sympathetic denervation (SDEN), a condition in which only muscle NE from both hindlimbs is depleted, transiently reduced the overall proteolysis and the UPS activity (∼25%) in both soleus and extensor digitorum longus muscles. This antiproteolytic response was accompanied by increased activity of adenylyl cyclase (112%), levels of cyclic adenosine monophosphate (cAMP; 191%), and the serine phosphorylation of cAMP response element-binding protein (32%). In extensor digitorum longus from normal rats, NE (10−4M) in vitro increased the levels of cAMP (115%) and the serine phosphorylation of both cAMP response element-binding protein (2.7-fold) and forkhead box class O1 transcription factor. Similar effects were observed in C2C12cells incubated with forskolin (10 μM). In parallel, NE significantly reduced the basal UPS (21%) activity and the mRNA levels of atrophy-related Ub-ligases. Similar responses were observed in isolated muscles exposed to 6-BNZ-cAMP (500 μM), a specific PKA activator. The phosphorylation levels of Akt were not altered by SDEN, NE, forskolin or 6-BNZ-cAMP. Our results demonstrate that SDEN induces muscle adrenergic supersensitivity for cAMP leading to the suppression of UPS, and that the suppressive effects of NE on UPS activity and expression of Ub-ligases can be mediated by the activation of cAMP/PKA signaling, with the inhibition of forkhead box class O1 transcription factor.
Slug Promotes Survival during Metastasis through Suppression of Puma-Mediated Apoptosis
Authors: Kim Seaho , Yao Jiahong , Suyama Kimita , Qian Xia , Qian Bin-Zhi , Bandyopadhyay Sanmay , Loudig Olivier , De Leon-Rodriguez Carlos , Zhou Zhen Ni , Segall Jeffrey , Macian Fernando , Norton Larry , Hazan Rachel B.
Published: May 2014

Tumor cells must overcome apoptosis to survive throughout metastatic dissemination and distal organ colonization. Here, we show in the Polyoma Middle T mammary tumor model that N-cadherin (Cdh2) expression causes Slug (Snai2) upregulation, which in turn promotes carcinoma cell survival. Slug was dramatically upregulated in metastases relative to primary tumors. Consistent with a role in metastasis, Slug knockdown in carcinoma cells suppressed lung colonization by decreasing cell survival at metastatic sites, but had no effect on tumor cell invasion or extravasation. In support of this idea, Slug inhibition by shRNA sensitized tumor cells to apoptosis by DNA damage, resulting in caspase-3 and PARP cleavage. The prosurvival effect of Slug was found to be caused by direct repression of the proapoptotic gene, Puma (Bbc3), by Slug. Consistent with a pivotal role for a Slug–Puma axis in metastasis, inhibition of Puma by RNA interference in Slug-knockdown cells rescued lung colonization, whereas Puma overexpression in control tumor cells suppressed lung metastasis. The survival function of the Slug–Puma axis was confirmed in human breast cancer cells, where Slug knockdown increased Puma expression and inhibited lung colonization. This study demonstrates a pivotal role for Slug in carcinoma cell survival, implying that disruption of the Slug–Puma axis may impinge on the survival of metastatic cells. Cancer Res; 74(14); 3695–706. ©2014 AACR.
Autophagy Inhibition by Sustained Overproduction of IL6 Contributes to Arsenic Carcinogenesis
Authors: Qi Yuanlin , Zhang Mingfang , Li Hui , Frank Jacqueline A. , Dai Lu , Liu Huijuan , Zhang Zhuo , Wang Chi , Chen Gang
Published: May 2014

Chronic inflammation has been implicated as an etiologic factor in cancer, whereas autophagy may help preserve cancer cell survival but exert anti-inflammatory effects. How these phenomenas interact during carcinogenesis remains unclear. We explored this question in a human bronchial epithelial cell–based model of lung carcinogenesis that is mediated by subchronic exposure to arsenic. We found that sustained overexpression of the pro-inflammatory IL6 promoted arsenic-induced cell transformation by inhibiting autophagy. Conversely, strategies to enhance autophagy counteracted the effect of IL6 in the model. These findings were confirmed and extended in a mouse model of arsenic-induced lung cancer. Mechanistic investigations suggested that mTOR inhibition contributed to the activation of autophagy, whereas IL6 overexpression was sufficient to block autophagy by supporting Beclin-1/Mcl-1 interaction. Overall, our findings argued that chronic inflammatory states driven by IL6 could antagonize autophagic states that may help preserve cancer cell survival and promote malignant progression, suggesting a need to uncouple inflammation and autophagy controls to enable tumor progression. Cancer Res; 74(14); 3740–52. ©2014 AACR.
Genome-wide Profiling of AP-1–Regulated Transcription Provides Insights into the Invasiveness of Triple-Negative Breast Cancer
Authors: Zhao Chunyan , Qiao Yichun , Jonsson Philip , Wang Jian , Xu Li , Rouhi Pegah , Sinha Indranil , Cao Yihai , Williams Cecilia , Dahlman-Wright Karin
Published: May 2014

Triple-negative breast cancer (TNBC) is an aggressive clinical subtype accounting for up to 20% of all breast cancers, but its malignant determinants remain largely undefined. Here, we show that in TNBC the overexpression of Fra-1, a component of the transcription factor AP-1, offers prognostic potential. Fra-1 depletion or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes of TNBC cells in vitro. Similarly, RNAi-mediated attenuation of Fra-1 or c-Jun reduced cellular invasion in vivo in a zebrafish tumor xenograft model. Exploring the AP-1 cistrome and the AP-1–regulated transcriptome, we obtained insights into the transcriptional regulatory networks of AP-1 in TNBC cells. Among the direct targets identified for Fra-1/c-Jun involved in proliferation, adhesion, and cell–cell contact, we found that AP-1 repressed the expression of E-cadherin by transcriptional upregulation of ZEB2 to stimulate cell invasion. Overall, this work illuminates the pathways through which TNBC cells acquire invasive and proliferative properties. Cancer Res; 74(14); 3983–94. ©2014 AACR.
Sialic Acids Sweeten a Tumor's Life
Authors: Büll Christian , Stoel Marieke A. , den Brok Martijn H. , Adema Gosse J.
Published: May 2014

Over four decades ago, specific tumor characteristics were ascribed to the increased expression of sialic acid sugars on the surface of cancer cells, and this led to the definition of sialic acids as potential therapeutic targets. Recent advances in glycobiology and cancer research have defined the key processes underlying aberrant expression of sialic acids in cancer, and its consequences, more precisely. These consequences include effects on tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. Collectively, these novel insights provide further rationale for the design and development of therapeutic approaches that interfere with excessively high expression of sialic acids in cancer cells. Strategies to target aberrant sialylation in cancer, however, have evolved comparatively slowly. Here, we review recent findings that emphasize the detrimental effects of hypersialylation on multiple aspects of tumor growth and behavior. We also discuss novel therapeutic strategies. Cancer Res; 74(12); 3199–204. ©2014 AACR.