bluuebunny/crossref_metadata_2025 huggingface dataset:
Percutaneous Cholecystostomy in High-Risk Elderly Patients With Acute Cholecystitis
Authors: Kapan Murat , Onder Akin , Tekbas Guven , Gul Mesut , Aliosmanoglu Ibrahim , Arikanoglu Zulfu , Aldemir Mustafa
Published: May 2012

Purpose:

To analyze the results of percutaneous cholecystostomy in in high-risk elderly patients with acute cholecystitis. Materials and Methods: Between June 2010 and May 2011, 11 patients aged over 60 who had at least 1 systemic disease and underwent percutaneous cholecystostomy were reviewed retrospectively.

Results:

The procedure was technically successful in 10 (90.9%) patients. Clinical improvement was achieved in 81.8% of patients within 72 hours. Two patients received emergency surgery while elective cholecystostomy was performed in 5 patients. Percutaneous cholecystostomy was performed singly in 4 (36.4%) patients. Early complication rate was 18.2%. Two (18.2%) patients died.

Conclusion:

Percutaneous cholecystostomy can be performed with low mortality and morbidity. Cholecystectomy should be performed in all patients with suitable general conditions due to the high recurrence rates of percutaneous cholecystostomy.
Gabapentin for Pruritus in Palliative care
Authors: Anand Sheeba
Published: May 2012

Itch/pruritus can be very distressing in palliative care population and often is difficult to treat. Conventional antihistamines lack efficacy. Cutaneous and central pathogenesis of itch is extremely complex and unclear, making its treatment challenging. Neuronal mechanisms have been identified in the pathophysiology of itch hence providing a myriad of therapeutic options. It has been established that pruritus and pain neuronal pathway interact with each other, hence neuropathic analgesics like gabapentin has shown to be efficacious antipruritic therapeutic option. Gabapentin impedes transmitting nociceptive sensations to brain, thus also suppressing pruritus. Gabapentin is safe and found to be effective in uremic pruritus, cancer/hematologic causes, opiod-induced itch, brachioradial pruritis, burns pruritus, and pruritus of unknown origin. Further research is required in this area to establish whether gabapentin is consistently effective.
Caring for Students With Type 1 Diabetes
Authors: Wang Yueh-Ling , Volker Deborah L.
Published: May 2012

This qualitative study used a Husserlian phenomenological approach to obtain an understanding of the essences of five experienced Taiwanese school nurses’ lived experience of caring for students with type 1 diabetes mellitus (T1DM). Audio-recorded, semi-structured, in-depth interviews were conducted. Data analysis entailed a modified method from Colaizzi. Four intertwined themes were discovered: (a) I try to put myself in the parents’ and students’ shoes, (b) I am not a diabetes expert, (c) managing T1DM requires teamwork, and (d) caring for students with T1DM is a struggle with practical limitations. The findings show that these school nurses encountered many challenges as they implemented their roles and responsibilities in caring for students with T1DM. The findings suggest that increasing school nurses’ competence in caring for students with T1DM and developing effective strategies to overcome the challenges faced may be useful. Multidisciplinary teamwork could benefit the diabetes management activities in school settings.
The In Vitro and In Vivo Genotoxicity of Benzocaine: A Brief Communication
Authors: Brock William J. , Bell Thomas A.
Published: May 2012

Benzocaine has a long history of use in human medicine. However, benzocaine also has been used in aquaculture with finfish for more than 40 years for sedating fish for marking, transport, surgery, and so on, although benzocaine does not have a current Food and Drug Administration (FDA) approval for this application in the United States. As part of a FDA approval for use as an animal drug, the genotoxicity of benzocaine was evaluated in the in vitro bacterial reverse mutation assay and the forward mutation assay and in vivo in the mouse micronucleus assay. These studies were conducted in compliance with Good Laboratory Practice regulations and according to Veterinary International Conference on Harmonisation guidelines. Based on the results of these studies, benzocaine was determined not to be genotoxic.
Meloxicam Modulates Oxidative Stress Status, Inhibits Prostaglandin E2, and Abrogates Apoptosis in Carbon Tetrachloride–Induced Rat Hepatic Injury
Authors: Edfawy Mohamed , Hassan Memy H. , Mansour Ahmed , Hamed Abdel-Aziz , Amin Hebat Allah A.
Published: May 2012

The current study aimed at investigating the potential hepatoprotective property and mechanism of meloxicam (MEL) against carbon tetrachloride (CCl4)-induced hepatocellular damage in rats. Subcutaneous administration of CCl4 (2 mL/kg, twice/week for 8 weeks) induced hepatocellular damage substantiated by hematoxylin and eosin staining and significant elevation in serum aspartate transaminase, alanine transaminase, and total bilirubin. In addition, CCL4 treatment led to elevation in liver contents of lipid peroxidation marker (malondialdehyde), prostaglandin E2, active caspase 3, and Terminal deoxynucleotidyl transferase dUTP nick end labeling–positive cells and reduction in the activities of superoxide dismutase, catalase, glutathione- S-transferase, and reduced glutathione in the liver tissue. Prior oral treatment with MEL (5 mg/kg, twice/week) retained the normal liver histology and significantly restored all of these parameters close to normal values. These results demonstrated the hepatoprotective utility of MEL against the CCl4-induced liver injury which might ascribe to its antioxidant, free radical scavenging, antiapoptotic and anti-inflammatory effects.
Positioning theory and practice question(s) within the field of management learning
Authors: Perriton Linda , Hodgson Vivien
Published: May 2012

In this paper we argue that management learning, as a field of study, has different choices to make than mainstream management research in its conceptualization and treatment of theory/practice. We believe that management learning as a field of practice – and as a journal – has both the opportunity, and a special responsibility, to consider theory and practice in ways that do not reduce the debate to disembodied actors and their assumed different occupational needs. Recent theoretical shifts in management learning have emphasized the relational, site and context specific conception of knowledge and practice and engaged with individuals (whatever their role) in exploring how they come to experience and develop new ways of being and acting in the world. We argue that management learning, when it looks at its existing practice through the epistemic practice perspective, will appreciate the contribution it is already making to advancing theory/practice understanding in management without needing to develop additional collaborative research strategies.
"Have Magic, Will Travel": Tourism and Harry Potter’s United (Magical) Kingdom
Authors: Lee Christina
Published: May 2012

This article examines the expanding global tourist trade for fictional places derived from popular narratives that are recreated for the tourist’s pleasure. Through a case study of a Harry Potter tour in the United Kingdom, I explore how the design of fantasy-themed ventures encourage a re-imagining of the landscape where (f)actual and imaginary geographies exist side by side. The locations function as affective, liminal spaces where the tourist anticipates and partakes in the transformation of sights/sites. Narrative and spatial engagement are crucial in producing a sense of embodied experience and an enchanted, and enchanting, reality where the realms of possibility are expanded.
Fear of difference: ‘Space of risk’ and anxiety in violent settings
Authors: Abu-Orf Hazem
Published: May 2012

Yosef Jabareen ties fear to planning in his empirical research conducted in Israel/Palestine, offering scholarly research in planning an important concept that is termed a ‘space of risk’. Yet, Jabareen’s research fails to outline the key theoretical aspects of fear which underpin his concept. The importance of fear to planning practice lies in helping planning scholars, and in particular those conducting research in cases of violent conflict, to understand the complexity that underpins spaces of anxiety, risk and threat. Analysis in this article therefore attempts to further conceptualise fear in planning theory, building upon and complementing Jabareen’s conceptualisation of a ‘space of risk’. A fresh area for scholarly research in planning theory emerges that addresses the politics of fear and the impact that fear has on the production of spaces in violent settings.
Patient and provider perceptions of sleep disordered breathing assessment during prenatal care: a survey-based observational study
Authors: Bourjeily Ghada , Raker Christina , Paglia Michael J. , Ankner Gina , O’Connor Kathleen
Published: May 2012

Objectives:

Screening for sleep disordered breathing (SDB) remains poor in the general population, despite evidence for association with adverse outcomes and improvement of certain outcomes with therapy. Data from the past decade have suggested an association between snoring and adverse pregnancy outcomes including gestational hypertensive disorders. However, it is unclear how often SDB is screened for in pregnancy. The objective of this study was to evaluate whether, and how, symptoms of SDB are assessed during prenatal care.

Methods:

This study was designed as a survey-based observational study. Within 48 hours of delivery, English-speaking patients were surveyed regarding prenatal conversations with obstetric providers about symptoms of SDB. During a similar time period, obstetric providers completed an anonymous questionnaire regarding how often they discussed the same symptoms during prenatal visits.

Results:

A total of 776 patients and 80 providers performing the majority of deliveries at the same hospital answered the survey. Nurse providers asked about sleep quality significantly more often than physician providers; however, responses to questions about snoring were similar in both groups. Resident physicians were the least likely to ask about sleep quality. Less than 3% of providers reported asking about snoring, closely matching patient responses. A total of 44% of patients surveyed were overweight and 21.7% were obese. Although 32% of patients snored, only 5% were asked about snoring during a prenatal visit. Obese women and women with a history of gestational hypertensive disorders were more likely to report being asked about snoring.

Conclusions:

Based on patient and obstetric provider recollections of discussions, the issue of SDB is poorly assessed during routine prenatal care, despite an increasing prevalence of overweight and obesity in the pregnant population.
Physical Limitation and Anger
Authors: Brown Robyn Lewis , Turner R. Jay
Published: May 2012

Is there a relationship between physical limitation and anger proneness? And, if so, is this relationship conditioned by associated differences in stress exposure and the availability of psychosocial coping resources? We explore these questions using data from a two-wave panel study including a representative sample of persons with and without physical limitations ( N = 1,473). Results of longitudinal change analysis demonstrate that physical limitation is associated with an increased tendency to both experience and express anger. Findings also reveal that this association is largely accounted for by variations in the experience of discrimination and differences in the psychosocial coping resources of mastery and self-esteem
Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a
Authors: Berent-Maoz Beata , Montecino-Rodriguez Encarnacion , Signer Robert A. J. , Dorshkind Kenneth
Published: May 2012

Involution of the thymus results in reduced production of naive T cells, and this in turn is thought to contribute to impaired immunity in the elderly. Early T-cell progenitors (ETPs), the most immature intrathymic T-cell precursors, harvested from the involuted thymus exhibit a diminished proliferative potential and increased rate of apoptosis and as a result their number is significantly reduced. In the present study, we show that these age-induced alterations result in part from increased expression of the Ink4a tumor-suppressor gene in ETPs. We also show that repression of Ink4a in aged ETPs results in their partial rejuvenation and that this can be accomplished by in vivo fibroblast growth factor 7 administration. These results define a genetic basis for thymocyte progenitor aging and demonstrate that the senescence-associated gene Ink4a can be pharmacologically repressed in ETPs to partially reverse the effects of aging.
An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma
Authors: Vij Ravi , Wang Michael , Kaufman Jonathan L. , Lonial Sagar , Jakubowiak Andrzej J. , Stewart A. Keith , Kukreti Vishal , Jagannath Sundar , McDonagh Kevin T. , Alsina Melissa , Bahlis Nizar J. , Reu Frederic J. , Gabrail Nashat Y. , Belch Andrew , Matous Jeffrey V. , Lee Peter , Rosen Peter , Sebag Michael , Vesole David H. , Kunkel Lori A. , Wear Sandra M. , Wong Alvin F. , Orlowski Robert Z. , Siegel David S.
Published: May 2012

Carfilzomib is a selective proteasome inhibitor that binds irreversibly to its target. In phase 1 studies, carfilzomib elicited promising responses and an acceptable toxicity profile in patients with relapsed and/or refractory multiple myeloma (R/R MM). In the present phase 2, multicenter, open-label study, 129 bortezomib-naive patients with R/R MM (median of 2 prior therapies) were separated into Cohort 1, scheduled to receive intravenous carfilzomib 20 mg/m2 for all treatment cycles, and Cohort 2, scheduled to receive 20 mg/m2 for cycle 1 and then 27 mg/m2 for all subsequent cycles. The primary end point was an overall response rate (≥ partial response) of 42.4% in Cohort 1 and 52.2% in Cohort 2. The clinical benefit response (overall response rate + minimal response) was 59.3% and 64.2% in Cohorts 1 and 2, respectively. Median duration of response was 13.1 months and not reached, and median time to progression was 8.3 months and not reached, respectively. The most common treatment-emergent adverse events were fatigue (62.0%) and nausea (48.8%). Single-agent carfilzomib elicited a low incidence of peripheral neuropathy—17.1% overall (1 grade 3; no grade 4)—in these pretreated bortezomib-naive patients. The results of the present study support the use of carfilzomib in R/R MM patients. This trial is registered at www.clinicaltrials.gov as NCT00530816.
Radiological and clinical outcomes of using Chartis™ to plan endobronchial valve treatment
Authors: Herth Felix J.F. , Eberhardt Ralf , Gompelmann Daniela , Ficker Joachim H. , Wagner Manfred , Ek Lars , Schmidt Bernd , Slebos Dirk-Jan
Published: May 2012

One-way endobronchial valves (EBVs) have been shown to relieve symptoms of emphysema, particularly in patients without collateral ventilation (CV) between the target and adjacent lobes. In this study, we investigated the ability of the bronchoscopic Chartis™ Pulmonary Assessment System to predict treatment response by determining the presence of CV.

80 EBV patients underwent a pre-treatment Chartis assessment. Before and 30 days after implantation, high-resolution computed tomography scans were taken to determine target lobe volume reduction (TLVR). A pre- to post-treatment reduction of ≥350 mL was defined as significant. In addition, clinical outcomes (forced expiratory volume in 1 s (FEV1), 6-min walk test and St George’s Respiratory Questionnaire) were compared over the same time period.

Of the 51 patients classified as having an absence of CV according to their Chartis reading, 36 showed a TLVR ≥350 mL. 29 patients were classified as having CV, and of these 24 did not meet this TLVR cut-off. Chartis showed an accuracy level of 75% in predicting whether or not the TLVR cut-off would be reached. Those predicted to respond showed significantly greater TLVR (p<0.0001) and FEV1improvement (p=0.0013) than those predicted not to respond.

Chartis is a safe and effective method of predicting response to EBV treatment.
Cerebral cortex oxygen delivery and exercise limitation in patients with COPD
Authors: Vogiatzis Ioannis , Louvaris Zafeiris , Habazettl Helmut , Andrianopoulos Vasileios , Wagner Harrieth , Roussos Charis , Wagner Peter D. , Zakynthinos Spyros
Published: May 2012

In healthy humans, cerebral oxygen desaturation during exercise affects motor unit recruitment, while oxygen supplementation enhances cerebral oxygenation and work capacity. It remains unknown whether in patients with chronic obstructive pulmonary disease (COPD), the well-documented improvement in exercise tolerance with oxygen supplementation may also be partly due to the increase in cerebral oxygenation.

Using near infrared spectroscopy, we measured both frontal cerebral cortex blood flow (CBF) using indocyanine green dye and cerebrovascular oxygen saturation (St,O2) in 12 COPD patients during constant-load exercise to exhaustion at 75% of peak capacity. Subjects exercised while breathing air, 100% oxygen or normoxic heliox, the latter two in balanced order.

Time to exhaustion while breathing air was less than for either oxygen or heliox (mean±sem394±35versus670±43 and 637±46 s, respectively). Under each condition, CBF increased from rest to exhaustion. At exhaustion, CBF was higher while breathing air and heliox than oxygen (30.9±2.3 and 31.3±3.5versus26.6±3.2 mL·min−1per 100 g, respectively), compensating for the lower arterial oxygen content (Ca,O2) in air and heliox, and leading to similar cerebral cortex oxygen delivery (CQO2for air was 5.3±0.4, for oxygen was 5.5±0.6 and for heliox was 5.6±1.0 mL O2per min per 100 g). In contrast, end-exerciseSt,O2was greater while breathing oxygen compared with air or heliox (67±4versus57±3 and 53±3%, respectively), reflecting Ca,O2rather than CQO2.

Prolonged time to exhaustion by breathing oxygen and heliox, despite these having a similar CQO2to air, a lowerSt,O2with heliox than oxygen, and yet similar endurance time and similarSt,O2in air and heliox despite greater endurance with heliox, do not support the hypothesis that an improvement in cerebral cortex oxygen availability plays a contributing role in increasing exercise capacity with oxygen or heliox in patients with COPD.
Vitamin D and skeletal muscle strength and endurance in COPD
Authors: Jackson Abigail S. , Shrikrishna Dinesh , Kelly Julia L. , Hart Nicholas , Moxham John , Polkey Michael I. , Kemp Paul , Hopkinson Nicholas S.
Published: May 2012

It is not known whether vitamin D levels make a significant contribution to muscle dysfunction in chronic obstructive pulmonary disease (COPD).

In 104 COPD patients (mean±sdforced expiratory volume in 1 s 44±22 % predicted) and 100 age- and sex-matched controls, serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH) levels were measured and related to quadriceps strength and endurance. In a subset of 26 patients and 13 controls, quadriceps biopsy was performed and mRNA expression of myogenic regulatory factors (mrf) and fibre-specific myosin heavy chains (MHC) was determined.

COPD patients were weaker and less physically active than controls. 25(OH)D levels were similar in both groups (48.5±25.5 nmol·L−1COPDversus55.4±28.3 nmol·L−1control, p=0.07) but PTH levels were significantly higher in patients (5.2±2.3 pmol·mL−1versus4.4±2.0 pmol·L−1, p=0.01). 1,25(OH)D was significantly correlated with strength in controls, but not in COPD patients and not with quadriceps endurance assessed using repetitive magnetic stimulation in COPD (n=35) or control (n=35) subjects. In controls, but not COPD patients, muscle biopsy analysis showed a negative relationship between 25(OH)D and MHCIIa expression (r2=0.5, p=0.01) and a positive relationship between mrf4 and MHCIIa expression (r2=0.5, p=0.009), and myogenic regulatory factor myf5 and MHCI expression (r2=0.72, p=0.004).

In contrast with healthy controls, muscle strength is not associated with vitamin D levels in COPD, which may represent vitamin D resistance.
Dissociation of electromyogram and mechanical response in sleep apnoea during propofol anaesthesia
Authors: Dotan Yaniv , Pillar Giora , Tov Nave , Oliven Ron , Steinfeld Uri , Gaitini Luis , Odeh Majed , Schwartz Alan R. , Oliven Arie
Published: May 2012

Pharyngeal collapsibility during sleep is believed to increase due to a decline in dilator muscle activity. However, genioglossus electromyogram (EMG) often increases during apnoeas and hypopnoeas, often without mechanical effect.

17 patients with obstructive sleep apnoea were anaesthetised and evaluated from termination of propofol administration to awakening. Genioglossus EMG, flow and pharyngeal area (pharyngoscopy) were monitored. Prolonged hypopnoeas enabled evaluation of the relationships between genioglossus EMG and mechanical events, before and after awakening. Additional dilator muscle EMGs were recorded and compared to the genioglossus. Electrical stimulation of the genioglossus was used to evaluate possible mechanical dysfunction.

Prolonged hypopnoeas during inspiration before arousal triggered an increase in genioglossus EMG, reaching mean±sd62.2±32.7% of maximum. This augmented activity failed to increase flow and pharyngeal area. Awakening resulted in fast pharyngeal enlargement and restoration of unobstructed flow, with marked reduction in genioglossus EMG. Electrical stimulation of the genioglossus under propofol anaesthesia increased the inspiratory pharyngeal area (from 25.1±28 to 66.3±75.5 mm2; p<0.01) and flow (from 11.5±6.5 to 18.6±9.2 L·min−1; p<0.001), indicating adequate mechanical response. All additional dilators increased their inspiratory activity during hypopnoeas.

During propofol anaesthesia, pharyngeal occlusion persists despite large increases in genioglossus EMG, in the presence of a preserved mechanical response to electrical stimulation.
Reduced lung function due to biomass smoke exposure in young adults in rural Nepal
Authors: Kurmi Om P. , Devereux Graham S. , Smith W. Cairns S. , Semple Sean , Steiner Markus F.C. , Simkhada Padam , Lam Kin-Bong Hubert , Ayres Jon G.
Published: May 2012

This study aimed to assess the effects of biomass smoke exposure on lung function in a Nepalese population, addressing some of the methodological issues seen in previous studies.

We carried out a cross-sectional study of adults in a population exposed to biomass smoke and a non-exposed population in Nepal. Questionnaire and lung function data were acquired along with direct measures of indoor and outdoor air quality.

Ventilatory function (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and forced expiratory flow at 25–75% of FVC) was significantly reduced in the population using biomass across all age groups compared to the non-biomass-using population, even in the youngest (16–25 yrs) age group (mean FEV1(95% CI) 2.65 (2.57–2.73)versus2.83 (2.74–2.91) L; p=0.004). Airflow obstruction was twice as common among biomass users compared with liquefied petroleum gas users (8.1%versus3.6%; p<0.001), with similar patterns for males (7.4%versus3.3%; p=0.022) and females (10.8%versus3.8%; p<0.001), based on the lower limit of normal. Smoking was a major risk factor for airflow obstruction, but biomass exposure added to the risk.

Exposure to biomass smoke is associated with deficits in lung function, an effect that can be detected as early as the late teenage years. Biomass smoke and cigarette smoke have additive adverse effects on airflow obstruction in this setting.
Hyperoxia disrupts pulmonary epithelial barrier in newborn rats via the deterioration of occludin and ZO-1
Authors: You Kai , Xu Xuewen , Fu Jianhua , Xu Shuyan , Yue Xiaohong , Yu Zhiling , Xue Xindong
Published: May 2012

Background

Prolonged exposure to hyperoxia in neonates can cause hyperoxic acute lung injury (HALI), which is characterized by increased pulmonary permeability and diffuse infiltration of various inflammatory cells. Disruption of the epithelial barrier may lead to altered pulmonary permeability and maintenance of barrier properties requires intact epithelial tight junctions (TJs). However, in neonatal animals, relatively little is known about how the TJ proteins are expressed in the pulmonary epithelium, including whether expression of TJ proteins is regulated in response to hyperoxia exposure. This study determines whether changes in tight junctions play an important role in disruption of the pulmonary epithelial barrier during hyperoxic acute lung injury.

Methods

Newborn rats, randomly divided into two groups, were exposed to hyperoxia (95% oxygen) or normoxia for 1–7 days, and the severity of lung injury was assessed; location and expression of key tight junction protein occludin and ZO-1 were examined by immunofluorescence staining and immunobloting; messenger RNA in lung tissue was studied by RT-PCR; transmission electron microscopy study was performed for the detection of tight junction morphology.

Results

We found that different durations of hyperoxia exposure caused different degrees of lung injury in newborn rats. Treatment with hyperoxia for prolonged duration contributed to more serious lung injury, which was characterized by increased wet-to-dry ratio, extravascular lung water content, and bronchoalveolar lavage fluid (BALF):serum FD4 ratio. Transmission electron microscopy study demonstrated that hyperoxia destroyed the structure of tight junctions and prolonged hyperoxia exposure, enhancing the structure destruction. The results were compatible with pathohistologic findings. We found that hyperoxia markedly disrupted the membrane localization and downregulated the cytoplasm expression of the key tight junction proteins occludin and ZO-1 in the alveolar epithelium by immunofluorescence. The changes of messenger RNA and protein expression of occludin and ZO-1 in lung tissue detected by RT-PCR and immunoblotting were consistent with the degree of lung injury.

Conclusions

These data suggest that the disruption of the pulmonary epithelial barrier induced by hyperoxia is, at least in part, due to massive deterioration in the expression and localization of key TJ proteins.
Effect of β2-adrenergic receptor gene (ADRB2) 3′ untranslated region polymorphisms on inhaled corticosteroid/long-acting β2-adrenergic agonist response
Authors: Ambrose Helen J , Lawrance Rachael M , Cresswell Carl J , Goldman Mitchell , Meyers Deborah A , Bleecker Eugene R
Published: May 2012

Background

Evidence suggests that variation in the length of the poly-C repeat in the 3′ untranslated region (3′UTR) of the β2-adrenergic receptor gene (ADRB2) may contribute to interindividual variation in β-agonist response. However, methodology in previous studies limited the assessment of the effect of sequence variation in the context of poly-C repeat length. The objectives of this study were to design a novel genotyping method to fully characterize sequence variation in the ADRB2 3′UTR poly-C repeat in asthma patients treated with inhaled corticosteroid and long-acting β2-adrenergic agonist (ICS/LABA) combination therapy, and to analyze the effect of the poly-C repeat polymorphism on clinical response.

Methods

In 2,250 asthma patients randomized to treatment with budesonide/formoterol or fluticasone/salmeterol in a six-month study (AstraZeneca study code: SD-039-0735), sequence diversity in the ADRB2 poly-C repeat region was determined using a novel sequencing-based genotyping method. The relationship between the poly-C repeat polymorphism and the incidence of severe asthma exacerbations, and changes in pulmonary function and asthma symptoms from baseline to the average during the treatment period, were analyzed.

Results

Poly-C repeat genotypes were assigned in 97% (2,192/2,250) of patients. Of the 13 different poly-C repeat alleles identified, six alleles occurred at a frequency of >5% in one or more population in this study. The repeat length of these six common alleles ranged from 10 to 14 nucleotides. Twelve poly-C repeat genotypes were observed at a frequency of >1%. No evidence of an association between poly-C repeat genotype and the incidence of severe asthma exacerbations was observed. Patients’ pulmonary function measurements improved and asthma symptoms declined when treated with ICS/LABA combination therapy regardless of poly-C repeat genotype.

Conclusions

The extensive sequence diversity present in the poly-C repeat region of the ADRB2 3′UTR did not predict therapeutic response to ICS/LABA therapy.
PhenoLink - a web-tool for linking phenotype to ~omics data for bacteria: application to gene-trait matching for Lactobacillus plantarum strains
Authors: Bayjanov Jumamurat R , Molenaar Douwe , Tzeneva Vesela , Siezen Roland J , van Hijum Sacha A F T
Published: May 2012

Background

Linking phenotypes to high-throughput molecular biology information generated by ~omics technologies allows revealing cellular mechanisms underlying an organism's phenotype. ~Omics datasets are often very large and noisy with many features (e.g., genes, metabolite abundances). Thus, associating phenotypes to ~omics data requires an approach that is robust to noise and can handle large and diverse data sets.

Results

We developed a web-tool PhenoLink (http://bamics2.cmbi.ru.nl/websoftware/phenolink/) that links phenotype to ~omics data sets using well-established as well new techniques. PhenoLink imputes missing values and preprocesses input data (i) to decrease inherent noise in the data and (ii) to counterbalance pitfalls of the Random Forest algorithm, on which feature (e.g., gene) selection is based. Preprocessed data is used in feature (e.g., gene) selection to identify relations to phenotypes. We applied PhenoLink to identify gene-phenotype relations based on the presence/absence of 2847 genes in 42Lactobacillus plantarumstrains and phenotypic measurements of these strains in several experimental conditions, including growth on sugars and nitrogen-dioxide production. Genes were ranked based on their importance (predictive value) to correctly predict the phenotype of a given strain. In addition to known gene to phenotype relations we also found novel relations.

Conclusions

PhenoLink is an easily accessible web-tool to facilitate identifying relations from large and often noisy phenotype and ~omics datasets. Visualization of links to phenotypes offered in PhenoLink allows prioritizing links, finding relations between features, finding relations between phenotypes, and identifying outliers in phenotype data. PhenoLink can be used to uncover phenotype links to a multitude of ~omics data, e.g., gene presence/absence (determined by e.g.: CGH or next-generation sequencing), gene expression (determined by e.g.: microarrays or RNA-seq), or metabolite abundance (determined by e.g.: GC-MS).
Effectiveness of a school-based physical activity-related injury prevention program on risk behavior and neuromotor fitness a cluster randomized controlled trial
Authors: Collard Dorine CM , Chinapaw Mai JM , Verhagen Evert ALM , Bakker Ingrid , van Mechelen Willem
Published: May 2012

Background

To investigate the effects of a school-based physical activity-related injury prevention program, called 'iPlay', on risk behavior and neuromotor fitness.

Methods

In this cluster randomized controlled trial 40 primary schools throughout the Netherlands were randomly assigned in an intervention (n = 20) or control group (n = 20). The study includes 2,210 children aged 10-12 years.

The iPlay-intervention takes one school year and consists of a teacher manual, informative newsletters and posters, a website, and simple exercises to be carried out during physical education classes.

Outcomes measures were self-reported injury preventing behavior, self-reported behavioral determinants (knowledge, attitude, social-influence, self-efficacy, and intention), and neuromotor fitness.

Results

The iPlay-program was not able to significantly improve injury-preventing behavior. The program did significantly improve knowledge and attitude, two determinants of behavior. The effect of the intervention-program on behavior appeared to be significantly mediated by knowledge and attitude. Improved scores on attitude, social norm, self-efficacy and intention were significantly related to changes in injury preventing behavior. Furthermore, iPlay resulted in small non-significant improvements in neuromotor fitness in favor of the intervention group.

Conclusion

This cluster randomized controlled trial showed that the iPlay-program did significantly improved behavioral determinants. However, this effect on knowledge and attitude was not strong enough to improve injury preventing behavior. Furthermore, the results confirm the hypothetical model that injury preventing behavior is determined by intention, attitude, social norm and self-efficacy.

Trial number

ISRCTN78846684
Significance of Conversation between Mast Cells and Nerves
Authors: van der Kleij Hanneke PM , Bienenstock John
Published: May 2012

More and more studies are demonstrating interactions between the nervous system and the immune system. However, the functional relevance of this interaction still remains to be elucidated. Such associations have been found in the intestine between nerves and mast cells as well as between eosinophils and plasma cells. Similar morphologic associations have been demonstrated in the liver, mesentery, urinary bladder, and skin. Unmyelinated axons especially were found to associate with mast cells as well as Langerhans' cells in primate as well as murine skin. Although there are several pathways by which immune cells interact with the nervous system, the focus in this review will be on the interaction between mast cells and nerves.
Food-Dependent Exercise-Induced Anaphylaxis: A Case Related to Chickpea Ingestion and Review
Authors: Wong Chet G. , Mace Sean R.
Published: May 2012

Food-dependent exercise-induced anaphylaxis (FDEIA) is recognized as a distinct category of exercise-induced anaphylaxis (EIA) but is very likely underdiagnosed. This report describes a 41-year-old Indian woman who experienced two separate episodes of anaphylaxis while dancing after she had eaten chickpea-containing foods. The chickpea, a small legume, is a staple ingredient in culinary traditions from around the world, especially in India, the Middle East, and North Africa. Chickpea-containing dishes are also becoming more widespread in the Western world with the growing popularity of South Asian, Middle Eastern, and African cuisines. It is important to consider FDEIA in cases of unexplained anaphylaxis as reactions can occur several hours after ingesting the culprit food(s). Furthermore, no reaction occurs if a sensitized individual eats the culprit food(s) without exercising afterward; therefore, triggering foods can easily be overlooked. Current ideas on the pathophysiology, predisposing factors, workup, and treatment of FDEIA are also summarized here.
Involvement of HTLV-I Tax and CREB in aneuploidy: a bioinformatics approach
Authors: de la Fuente Cynthia , Gupta Madhur V , Klase Zachary , Strouss Katharine , Cahan Patrick , McCaffery Timothy , Galante Anthony , Soteropoulos Patricia , Pumfery Anne , Fujii Masahiro , Kashanchi Fatah
Published: May 2012

Background

Adult T-cell leukemia (ATL) is a complex and multifaceted disease associated with human T-cell leukemia virus type 1 (HTLV-I) infection. Tax, the viral oncoprotein, is considered a major contributor to cell cycle deregulation in HTLV-I transformed cells by either directly disrupting cellular factors (protein-protein interactions) or altering their transcription profile. Tax transactivates these cellular promoters by interacting with transcription factors such as CREB/ATF, NF-κB, and SRF. Therefore by examining which factors upregulate a particular set of promoters we may begin to understand how Tax orchestrates leukemia development.

Results

We observed that CTLL cells stably expressing wild-type Tax (CTLL/WT) exhibited aneuploidy as compared to a Tax clone deficient for CREB transactivation (CTLL/703). To better understand the contribution of Tax transactivation through the CREB/ATF pathway to the aneuploid phenotype, we performed microarray analysis comparing CTLL/WT to CTLL/703 cells. Promoter analysis of altered genes revealed that a subset of these genes contain CREB/ATF consensus sequences. While these genes had diverse functions, smaller subsets of genes were found to be involved in G2/M phase regulation, in particular kinetochore assembly. Furthermore, we confirmed the presence of CREB, Tax and RNA Polymerase II at the p97Vcp and Sgt1 promoters in vivo through chromatin immunoprecipitation in CTLL/WT cells.

Conclusion

These results indicate that the development of aneuploidy in Tax-expressing cells may occur in response to an alteration in the transcription profile, in addition to direct protein interactions.
Elevated levels of vitamin D and deficiency of mannose binding lectin in dengue hemorrhagic fever
Authors: Alagarasu Kalichamy , Bachal Rupali V , Bhagat Asha B , Shah Paresh S , Dayaraj Cecilia
Published: May 2012

Background

Altered plasma concentrations of vitamin D and mannose binding lectin (MBL), components of innate immunity, have been shown to be associated with the pathogenesis of viral infections. The objective of the present study was to find out whether plasma concentrations of MBL and vitamin D are different in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF).

The results

The plasma concentrations of vitamin D and MBL were assessed in 48 DF cases, 45 DHF cases and 20 apparently healthy controls using ELISA based methods. Vitamin D concentrations were found to be higher among both DF and DHF cases as compared to healthy controls (P < 0.005 and P < 0.001). Vitamin D concentrations were not different between DF and DHF cases. When the dengue cases were classified into primary and secondary infections, secondary DHF cases had significantly higher concentrations of vitamin D as compared to secondary DF cases (P < 0.050). MBL concentrations were not significantly different between healthy controls and dengue cases. MBL concentrations were observed to be lower in DHF cases as compared to DF cases (P < 0.050). Although MBL levels were not different DF and DHF cases based on immune status, the percentage of primary DHF cases (50%) having MBL levels lower than 500 ng/ml were less compared to primary DF cases (P = 0.038).

Conclusions

The present study suggests that higher concentrations of vitamin D might be associated with secondary DHF while deficiency of MBL may be associated with primary DHF.
A conserved histone deacetylase with a role in the regulation of cytokinesis in Schizosaccharomyces pombe
Authors: Grewal Charnpal , Hickmott Jack , Rentas Stefan , Karagiannis Jim
Published: May 2012

Background

In Schizosaccharomyces pombe the SET domain protein, Set3p - together with its interacting partners, Snt1p, and Hif2p - form a complex that aids in preventing cell division failure upon mild cytokinetic stress. Intriguingly, the human orthologs of these proteins (MLL5, NCOR2, and TBL1X) are also important for the faithful completion of cytokinesis in tissue culture cells. Since MLL5, NCOR2, and TBL1X form a complex with the histone deacetylase, HDAC3, we sought to determine if an orthologous counterpart played a regulatory role in fission yeast cytokinesis.

Results

In this report we identify the hos2 gene as the fission yeast HDAC3 ortholog. We show that Hos2p physically interacts with Set3p, Snt1p, and Hif2p, and that hos2∆ mutants are indeed compromised in their ability to reliably complete cell division in the presence of mild cytokinetic stresses. Furthermore, we demonstrate that over-expression of hos2 causes severe morphological and cytokinetic defects. Lastly, through recombinase mediated cassette exchange, we show that expression of human HDAC3 complements the cytokinetic defects exhibited by hos2∆ cells.

Conclusions

These data support a model in which Hos2p functions as an essential component of the Set3p-Snt1p-Hif2p complex with respect to the regulation of cytokinesis. The ability of human HDAC3 to complement the cytokinesis defects associated with the deletion of the hos2 gene suggests that further analysis of this system could provide insight into the role of HDAC3 in both the regulation of cell division, as well as other biological processes influenced by HDAC3 deacetylation.
Retinaldehyde Dehydrogenase 1 Coordinates Hepatic Gluconeogenesis and Lipid Metabolism
Authors: Kiefer Florian W. , Orasanu Gabriela , Nallamshetty Shriram , Brown Jonathan D. , Wang Hong , Luger Philip , Qi Nathan R. , Burant Charles F. , Duester Gregg , Plutzky Jorge
Published: May 2012

Recent data link vitamin A and its retinoid metabolites to the regulation of adipogenesis, insulin sensitivity, and glucose homeostasis. Retinoid metabolism is tightly controlled by an enzymatic network in which retinaldehyde dehydrogenases (Aldh1–3) are the rate-limiting enzymes that convert retinaldehyde to retinoic acid. Aldh1a1-deficient mice are protected from diet-induced obesity and hence diabetes. Here we investigated whether Aldh1a1 and the retinoid axis regulate hepatic glucose and lipid metabolism independent of adiposity. The impact of Aldh1a1 and the retinoid pathway on glucose homeostasis and lipid metabolism was analyzed in hepatocytes in vitro and in chow-fed, weight-matched Aldh1a1-deficient vs. wild-type (WT) mice in vivo. Aldh1a1-deficient mice displayed significantly decreased fasting glucose concentrations compared with WT controls as a result of attenuated hepatic glucose production. Expression of key gluconeogenic enzymes as well as the activity of Forkhead box O1 was decreased in Aldh1a1-deficient vs. WT livers. In vitro, retinoid or cAMP agonist stimulation markedly induced gluconeogenesis in WT but not Aldh1a1-deficient primary hepatocytes. Aldh1a1 deficiency increased AMP-activated protein kinase α activity, decreased expression of lipogenic targets of AMP-activated protein kinase α and significantly attenuated hepatic triacylglycerol synthesis. In metabolic cage studies, lean Aldh1a1-deficient mice manifested enhanced oxygen consumption and reduced respiratory quotient vs. WT controls, consistent with increased expression of fatty acid oxidation markers in skeletal muscle. Taken together, this work establishes a role for retinoid metabolism in glucose homeostasis in vivo and for Aldh1a1 as a novel determinant of gluconeogenesis and lipid metabolism independent of adiposity.
Measuring the Output Responses to Fiscal Policy
Authors: Auerbach Alan J , Gorodnichenko Yuriy
Published: May 2012

A key issue in current research and policy is the size of fiscal multipliers when the economy is in recession. We provide three insights. First, using regime-switching models, we find large differences in the size of spending multipliers in recessions and expansions with fiscal policy being considerably more effective in recessions than in expansions. Second, we estimate multipliers for more disaggregate spending variables which behave differently relative to aggregate fiscal policy shocks, with military spending having the largest multiplier. Third, we show that controlling for predictable components of fiscal shocks tends to increase the size of the multipliers in recessions. (JEL C32, E62, H20, H62, H63)
Empirical Evidence on the Aggregate Effects of Anticipated and Unanticipated US Tax Policy Shocks
Authors: Mertens Karel , Ravn Morten O
Published: May 2012

We provide evidence on the dynamic effects of tax liability changes in the United States. We distinguish between surprise and anticipated tax changes. Preannounced but not yet implemented tax cuts give rise to contractions in output, investment, and hours worked while real wages increase. There are no significant anticipation effects on aggregate consumption. Implemented tax cuts, regardless of their timing, have expansionary effects, on output, consumption, investment, hours worked, and real wages. Results are shown to be robust. Tax shocks are important impulses to the US business cycle and anticipation effects have been important during several business cycle episodes. (JEL E23, E32, E62, H20, H30)
Measuring Tax Multipliers: The Narrative Method in Fiscal VARs
Authors: Favero Carlo , Giavazzi Francesco
Published: May 2012

This paper argues in favor of empirical models built by including in fiscal VAR models structural shocks identified via the narrative method. We first show that “narrative” shocks are orthogonal to the relevant information set a fiscal VAR. We then derive impulse responses to these shocks. The use of narrative shocks does not require the inversion of the moving-average representation of a VAR for the identification of the relevant shocks. Therefore, within this framework, fiscal multipliers can be identified and estimated even when, in the presence of “fiscal foresight,” the MA representation of the VARs is not invertible. (JEL C32, E62, H20, H62, H63)
Global Savings and Global Investment: The Transmission of Identified Fiscal Shocks
Authors: Feyrer James , Shambaugh Jay
Published: May 2012

This paper examines the effect of exogenous shocks to savings on world capital markets. Exogenous tax increases in the United States (from Romer and Romer 2010) are only partially offset by changes in domestic private savings, and only a small amount is absorbed by increased domestic investment (contra Feldstein and Horioka 1980). Almost half the change in taxes is transmitted abroad through a change in the US current account. Other countries experience decreases in current accounts and increases in investment in response to exogenous US tax increases. We cannot reject symmetric responses across countries with different currency regimes and levels of development. (JEL E21, E22, E23, E62, F32, F42)
Modeling Airline Frequency Competition for Airport Congestion Mitigation
Authors: Vaze Vikrant , Barnhart Cynthia
Published: May 2012

Demand often exceeds capacity at congested airports. Airline frequency competition is partially responsible for the growing demand for airport resources. We propose a game-theoretic model for airline frequency competition under slot constraints. The model is solved to obtain a Nash equilibrium using a successive optimizations approach, wherein individual optimizations are performed using a dynamic programming-based technique. The model predictions are validated against actual frequency data, with the results indicating a close fit to reality. We use the model to evaluate different strategic slot allocation schemes from the perspectives of the airlines and the passengers. The most significant result of this research shows that a small reduction in the total number of allocated slots translates into a substantial reduction in flight and passenger delays and also a considerable improvement in airlines' profits.