bluuebunny/crossref_metadata_2025 huggingface dataset:
The meaning of resilience to persons living with chronic pain: an interpretive qualitative inquiry
Authors: West Caryn , Stewart Lee , Foster Kim , Usher Kim
Published: March 2012

Aim.  The purpose of this study was to explore the meaning of resilience, or adaptation in the face of adversity, to people living with chronic pain.

Background.  Little research on the usefulness of resilience, strength‐based approach to health care has been undertaken to date in the area of pain yet this approach has recently been proposed as a new model for chronic pain management. However, the meaning of resilience to people with chronic pain remains unknown.

Design.  An interpretive qualitative design using in‐depth interviews and phenomenological type analysis was undertaken.

Methods.  Purposive sampling and in‐depth interviewing were undertaken to develop a rich description of the experience.

Results.  The findings from this study revealed that while living with chronic pain is generally a negative experience, the participants also told positive stories around the following themes: (i) Recognising individual strength; (ii) Looking for the positives in life; (iii) Accepting the pain; and (iv) Learning to accept help.

Conclusion.  Chronic pain influences all aspects of life. Resilient individuals with chronic pain recognise the value of remaining positive, accepting help and learning to live with the pain.

Relevance to clinical practice.  It is important for health professionals to recognise the role of supporting positive attributes in people living with chronic pain as a way of enhancing resilience.
Sensorimotor cortical activation in patients with sleep bruxism
Authors: KERVANCIOGLU BEDIA B. , TEISMANN INGA K. , RAIN MELANIE , HUGGER SYBILLE , BOECKMANN JOANNE A. , YOUNG PETER , SCHWINDT WOLFRAM , PANTEV CHRISTO , DOERING STEPHAN
Published: March 2012

Sleep bruxism is assumed to be triggered by a dysfunctional subcortical and cortical network. This study investigates sensorimotor cortical activation in patients with sleep bruxism during clenching and chewing. Nine polysomnographically diagnosed patients and nine healthy control subjects underwent magnetoencephalography (MEG). During clenching and chewing, patients with bruxism revealed significantly larger event‐related desynchronization in the somatomotor area (Brodmann area 4) than healthy subjects. Group differences in the muscle activity were ruled out by electromyography (EMG) assessments during MEG. This result might be regarded as a consequence of increased sensorimotor cortical representation of the tongue and chewing musculature due to an enhanced parafunctional muscle activity in bruxers potentially triggered by occlusal factors. Alternatively, a secondary activation of cortical structures during sleep bruxism in the context of an activated network of subcortical and cortical structures might lead to increased cortical representation of the chewing musculature via use dependent plasticity.
A practical guide for the use of boceprevir and telaprevir for the treatment of hepatitis C
Authors: Jacobson I. M. , Pawlotsky J.‐M. , Afdhal N. H. , Dusheiko G. M. , Forns X. , Jensen D. M. , Poordad F. , Schulz J.
Published: March 2012

Summary.  The aim of this study is to review clinical trial data on the newly approved protease inhibitors boceprevir and telaprevir to develop consensus recommendations on the optimal use of these agents for the treatment of patients with chronic hepatitis C virus (HCV) infection. An expert panel of seven leading authorities in viral hepatitis was convened to establish and disseminate a practical guide on best practices for incorporating boceprevir and telaprevir into therapy for HCV infection in both treatment‐naive and treatment‐experienced patients. The topics covered include selecting candidates for boceprevir‐ or telaprevir‐based treatments, predictors of response and early viral kinetics, response‐guided therapy approaches, on‐treatment management strategies to optimize the likelihood of response and minimize the risk of drug resistance, management of adverse effects during therapy and key considerations for special populations. The expert panel incorporated the best available clinical evidence into recommendations on how boceprevir and telaprevir should be used in the clinical setting. They indicated how treatment regimens may differ according to the baseline factors, such as presence of cirrhosis and when therapy may need to be modified or stopped altogether because of adverse events or poor virologic response. This practical guide will serve as a valuable resource for clinicians embarking on the new treatment paradigm of boceprevir or telaprevir in combination with peginterferon/ribavirin for chronic genotype 1 HCV infection.
A RelA‐dependent two‐tiered regulated proteolysis cascade controls synthesis of a contact‐dependent intercellular signal in Myxococcus xanthus
Authors: Konovalova Anna , Löbach Stephanie , Søgaard‐Andersen Lotte
Published: March 2012

Proteolytic cleavage of precursor proteins to generate intercellular signals is a common mechanism in all cells. In Myxococcus xanthus the contact‐dependent intercellular C‐signal is a 17 kDa protein (p17) generated by proteolytic cleavage of the 25 kDa csgA protein (p25), and is essential for starvation‐induced fruiting body formation. p25 accumulates in the outer membrane and PopC, the protease that cleaves p25, in the cytoplasm of vegetative cells. PopC is secreted in response to starvation, therefore, restricting p25 cleavage to starving cells. We focused on identifying proteins critical for PopC secretion in response to starvation. PopC secretion depends on the (p)ppGpp synthase RelA and the stringent response, and is regulated post‐translationally. PopD, which is encoded in an operon with PopC, forms a soluble complex with PopC and inhibits PopC secretion whereas the integral membrane AAA+ protease FtsHD is required for PopC secretion. Biochemical and genetic evidence suggest that in response to starvation, RelA is activated and induces the degradation of PopD thereby releasing pre‐formed PopC for secretion and that FtsHD is important for PopD degradation. Hence, regulated PopC secretion depends on regulated proteolysis. Accordingly, p17 synthesis depends on a proteolytic cascade including FtsHD‐dependent degradation of PopD and PopC‐dependent cleavage of p25.
Influence of liver‐disease etiology on long‐term quality of life and employment after liver transplantation
Authors: Åberg Fredrik , Höckerstedt Krister , Roine Risto P. , Sintonen Harri , Isoniemi Helena
Published: March 2012

The etiology of liver disease would expectedly affect health‐related quality of life (HRQoL) and employment after liver transplantation (LT), but studies are scarce. We sent the 15D HRQoL instrument and an employment questionnaire to all 401 adult LT patients alive in Finland in 2007. The response rate was 89% (n = 353; mean of eight yr since LT). In age‐adjusted analysis, patients transplanted for primary sclerosing cholangitis (PSC; n = 56), primary biliary cirrhosis (PBC; n = 72), acute liver failure (ALF; n = 76), alcoholic cirrhosis (n = 38), or liver tumor (n = 22) exhibited comparable HRQoL, whereas the combined group of miscellaneous chronic liver diseases (n = 89) exhibited significantly higher HRQoL scores (p = 0.003). Among working‐aged patients (20–65 yr at LT), employment rates were highest in the PSC (56%) group and lowest in the ALF (39%) and PBC (29%) groups. In age‐adjusted logistic regression, patients with PSC or alcoholic cirrhotics were 2.4‐ and 2.5‐fold more likely to resume work after LT than patients with PBC. In conclusion, HRQoL scores late after LT were in general relatively high and comparable among disease groups. Patients with PSC or alcoholic cirrhosis were most likely to resume work after LT. The relatively low employment among patients with ALF may merit enhanced rehabilitation efforts.
Multiple cis‐regulatory elements are involved in the complex regulation of the sieve element‐specific MtSEO‐F1 promoter from Medicago truncatula
Authors: Bucsenez M. , Rüping B. , Behrens S. , Twyman R. M. , Noll G. A. , Prüfer D.
Published: March 2012

The sieve element occlusion (SEO) gene family includes several members that are expressed specifically in immature sieve elements (SEs) in the developing phloem of dicotyledonous plants. To determine how this restricted expression profile is achieved, we analysed the SE‐specific Medicago truncatula SEO‐F1 promoter (PMtSEO‐F1) by constructing deletion, substitution and hybrid constructs and testing them in transgenic tobacco plants using green fluorescent protein as a reporter. This revealed four promoter regions, each containing cis‐regulatory elements that activate transcription in SEs. One of these segments also contained sufficient information to suppress PMtSEO‐F1 transcription in the phloem companion cells (CCs). Subsequent in silico analysis revealed several candidate cis‐regulatory elements that PMtSEO‐F1 shares with other SEO promoters. These putative sieve element boxes (PSE boxes) are promising candidates for cis‐regulatory elements controlling the SE‐specific expression of PMtSEO‐F1.
Isolation and characterisation of Chrysanthemum crassum SOS1, encoding a putative plasma membrane Na+/H+ antiporter
Authors: Song A. , Lu J. , Jiang J. , Chen S. , Guan Z. , Fang W. , Chen F.
Published: March 2012

A full‐length cDNA homologue of SOS1 (salt overly sensitive 1) was isolated from the salinity‐tolerant species Chrysanthemum crassum and found to encode a Na+/H+ antiporter, using degenerate PCR and RACE‐PCR. The 3752‐bp sequence comprised a 3438 bp open reading frame, encoding a 127‐kDa protein with 12 transmembrane domains within its N terminal portion, and a hydrophilic cytoplasmic tail in its C‐terminal portion. CcSOS1 appears to be a plasma membrane protein, and shares ∼62% identity at the peptide level with its Arabidopsis thaliana homologue. Expression of CcSOS1 in the roots of C. crassum was sensitive to salinity stress, while in the leaves CcSOS1 was down‐regulated in the presence of abscisic acid. CcSOS1 transcript abundance was reduced in both roots and leaves of plants exposed to low temperature, while it was increased in leaves (but not in roots) after drought stress. CcSOS1 expression was not regulated in the presence of CaCl2. A heterologous complementation assay in yeast suggested that CcSOS1 directs Na+ efflux, mimicking the function of the endogenous NHA1 protein. Thus CcSOS1 appears to encode a salinity‐inducible plasma membrane Na+/H+ antiporter. This gene may be useful in transgenic approaches to improving the salinity tolerance of related ornamental species.
Seasonal, sex and live weight variations in feed and water consumptions of adult captive African Giant rats (Cricetomys gambianus, Waterhouse – 1840) kept individually in cages
Authors: Dzenda T. , Ayo J. O. , Lakpini C. A. M. , Adelaiye A. B.
Published: March 2012

Adult African Giant rats (Cricetomys gambianus, Waterhouse) (AGRs) (n = 231) of both sexes (117 bucks, 114 does) were live‐trapped in the wild in Zaria, Nigeria. Live weight (LW), daily feed consumption (FC) and water consumption (WC) of the AGRs were measured during the cold‐dry (CDS), hot‐dry (HDS) and rainy (RS) seasons for 2 years with the aim of determining seasonal, sex and LW variations. Feed consumption was significantly different (p < 0.001) between all the seasons, with the lowest mean value recorded during the HDS, while the highest was obtained during the RS. Water consumption was also lowest (p < 0.001) during the HDS but did not differ significantly (p > 0.05) between the CDS and RS. Both feed and water consumptions were higher (p < 0.01) in the males (bucks) than the females (does) during the CDS and HDS, but the sex difference was not significant (p > 0.05) during the RS. Feed consumption correlated positively (p < 0.0001) with WC and relative humidity, but negatively (p < 0.0001) with LW, ambient temperature and heat index. In conclusion, both feed and water consumptions in AGRs decrease with increased seasonal heat and adult LW and are lower in does than in bucks during the dry seasons (CDS and HDS). Intervention may be indicated during the HDS to improve feed and water consumptions for optimal performance of the AGRs.
Comparison of two exhaled nitric oxide analyzers: The NIOX MINO hand‐held electrochemical analyzer and the NOA280i stationary chemiluminescence analyzer
Authors: KIM SANG‐HEON , MOON JI‐YONG , KWAK HYUN JUNG , KIM SA IL , PARK DONG WON , KIM JEE WOO , KIM TAE HYUNG , SOHN JANG WON , SHIN DONG HO , PARK SUNG SOO , YOON HO JOO
Published: March 2012

Background and objective:  Measurement of the fraction of nitric oxide (FeNO) in exhaled air is useful in the management of asthma. A new hand‐held nitric oxide (NO) analyzer, the NIOX MINO, is simple and easy to use in clinical practice. In this study, FeNO values measured using the NIOX MINO were compared with those obtained using a stationary chemiluminescence analyzer, the Sievers NOA280i.

Methods:  FeNO was measured in 100 adults, using both the NIOX MINO and the NOA280i. Nine (9.0%) of these subjects had asthma. The first acceptable measurement with the NIOX MINO and the mean of two acceptable measurements with the NOA280i were compared.

Results:  There was a significant correlation between FeNO concentrations measured with the two devices (r = 0.876, P < 0.001). A Bland–Altman plot showed a high degree of agreement between the two devices: the mean inter‐device difference was 3.3 parts per billion (ppb), and the 95% limits of agreement were −7.0 and 13.6 ppb. In addition, the mean relative difference was 14.5%, with the 95% limits of agreement being −33.7 and 62.7%. The mean value (± standard error of the mean) for FeNO as measured with the NIOX MINO (18.8 ± 0.9 ppb) was significantly lower than that measured with the NOA280i (22.1 ± 1.2 ppb, P < 0.001).

Conclusions:  There was a significant correlation, but only moderate agreement, between FeNO values measured with the NIOX MINO and those measured with the NOA280i, with the NIOX MINO values being significantly lower than the NOA280i values. Significant differences in FeNO values obtained with these two NO analyzers should be considered when interpreting the results of FeNO measurements.
Genomics and the respiratory effects of air pollution exposure
Authors: HOLLOWAY JOHN W. , SAVARIMUTHU FRANCIS SANTIYAGU , FONG KWUN M. , YANG IAN A.
Published: March 2012

Adverse health effects from air pollutants remain important, despite improvement in air quality in the past few decades. The exact mechanisms of lung injury from exposure to air pollutants are not yet fully understood. Studying the genome (e.g. single‐nucleotide polymorphisms (SNP) ), epigenome (e.g. methylation of genes), transcriptome (mRNA expression) and microRNAome (microRNA expression) has the potential to improve our understanding of the adverse effects of air pollutants. Genome‐wide association studies of SNP have detected SNP associated with respiratory phenotypes; however, to date, only candidate gene studies of air pollution exposure have been performed. Changes in epigenetic processes, such DNA methylation that leads to gene silencing without altering the DNA sequence, occur with air pollutant exposure, especially global and gene‐specific methylation changes. Respiratory cell line and animal models demonstrate distinct gene expression signatures in the transcriptome, arising from exposure to particulate matter or ozone. Particulate matter and other environmental toxins alter expression of microRNA, which are short non‐coding RNA that regulate gene expression. While it is clearly important to contain rising levels of air pollution, strategies also need to be developed to minimize the damaging effects of air pollutant exposure on the lung, especially for patients with chronic lung disease and for people at risk of future lung disease. Careful study of genomic responses will improve our understanding of mechanisms of lung injury from air pollution and enable future clinical testing of interventions against the toxic effects of air pollutants.
Correlation between circulating fibrocytes, and activity and progression of interstitial lung diseases
Authors: FUJIWARA ATSUSHI , KOBAYASHI HIROYASU , MASUYA MASAHIRO , MARUYAMA MITSUKO , NAKAMURA SHIHO , IBATA HIDENORI , FUJIMOTO HAJIME , OHNISHI MASAHIRO , URAWA MASAHITO , NAITO MASAHIRO , TAKAGI TAKEHIRO , KOBAYASHI TETSU , GABAZZA ESTEBAN C. , TAKEI YOSHIYUKI , TAGUCHI OSAMU
Published: March 2012

Background and objective:  Interstitial lung diseases (ILD) are characterized by progressive interstitial pulmonary fibrosis and a decline in lung function. Fibrocytes are bone marrow‐derived mesenchymal progenitor cells that may play a role in the pathogenesis of pulmonary fibrosis. Circulating fibrocyte numbers have been correlated with the prognosis of patients with idiopathic pulmonary fibrosis. The aim of the present study was to evaluate the relationship between circulating fibrocytes, and parameters of disease activity and progression in several groups of patients with ILD.

Methods:  The study population comprised 41 patients with ILD and seven healthy control subjects. Circulating CD45+ collagen‐I+ fibrocytes were evaluated by flow cytometry.

Results:  The number of circulating fibrocytes was significantly increased in all patients with ILD and particularly in patients with idiopathic interstitial pneumonitis and interstitial pneumonitis associated with collagen vascular disease as compared with healthy control subjects. The numbers of circulating fibrocytes were significantly correlated with pulmonary function test parameters and with serum levels of sialylated carbohydrate antigen, a marker of disease activity. Temporal changes in circulating fibrocyte numbers were evaluated in two patients, and the results suggested that these changes correlated with the activity of ILD.

Conclusions:  The results from this study provide further evidence for the role of circulating fibrocytes in fibrotic lung diseases.
Novel posterior reconstruction technique during robot‐assisted laparoscopic prostatectomy: Description and comparative outcomes
Authors: Jeong Chang Wook , Oh Jong Jin , Jeong Seong Jin , Hong Sung Kyu , Byun Seok‐Soo , Choe Gheeyoung , Lee Sang Eun
Published: March 2012

The aim of the present study was to assess the impact of a novel posterior reconstruction technique during robot‐assisted laparoscopic prostatectomy on continence recovery. A total of 116 consecutive patients who received the novel posterior reconstruction (case group) were retrospectively compared with a cohort of 126 patients who did not receive posterior reconstruction (control group). The primary end‐point was the duration of continence recovery (no pad use) after robot‐assisted laparoscopic prostatectomy. The posterior reconstruction was obtained by opposing the median dorsal fibrous raphe to the posterior counterpart of the detrusor apron, rather than the Denonvilliers' fascia. The case group showed higher continence rates at all points of evaluation, which were 2 weeks (30.1% vs 19.8%), 1 month (58.4% vs 45.7%), 3 months (82.7% vs 70.5%) and 6 months postoperatively (95.3% vs 86.4%) (P = 0.007). Application of the novel posterior reconstruction technique, age and length of membranous urethra were significant variables for the complete recovery of continence on multivariable analysis. This study shows that the application of this novel PR technique significantly improves the recovery of continence in patients undergoing robot‐assisted laparoscopic prostatectomy.
Fatigue assessment and failure analysis of shot‐peened leaf springs
Authors: FRAGOUDAKIS R. , SAIGAL A. , SAVAIDIS G. , MALIKOUTSAKIS M. , BAZIOS I. , SAVAIDIS A. , PAPPAS G. , KARDITSAS S.
Published: March 2012

The paper deals with the fatigue and failure analysis of serial shot‐peened leaf springs of heavy trucks emphasizing on the influence of thermal treatment and shot peening on fatigue life. Experimental stress–life curves are determined by investigating smooth specimens subjected to fully reversed rotating bending conditions. These test results are compared to corresponding ones determined from cyclic three‐point bend tests on shot‐peened serial leaf springs in order to reveal the influence of the applied thermal treatment and shot peening process on the fatigue life of the high‐strength steel used for leaf spring manufacturing, dependent on the load level. Microstructure, macro‐ and micro‐hardness analyses are performed to support the analyses and explain the effects resulting from the certain shot peening process on the surface properties of the high‐strength spring steel under investigation. The assessment of the fatigue results reveals nearly no life improvement due to the manufacturing, emphasizing the necessity for mutual adjustment of shot peening and thermal treatment parameters to take account for life improvement.
An energy‐based critical fatigue life prediction method for AL6061‐T6
Authors: LETCHER T. , SHEN M.‐H. H. , SCOTT‐EMUAKPOR O. , GEORGE T. , CROSS C.
Published: March 2012

An energy‐based critical fatigue life prediction method is developed and analysed. The original energy‐based fatigue life prediction theory states that the number of cycles to failure is estimated by dividing the total energy accumulated during a monotonic fracture by the strain energy per cycle. Because the accuracy of this concept is heavily dependent on the cyclic behaviour of the material, a precise understanding of the strain energy behaviour throughout each failure process is necessary. Examination of the stress and strain during fatigue tests shows that the cyclic strain energy behaviour is not perfectly stable as initially presumed. It was discovered that fatigue hysteresis energy always accumulates to the same amount of energy by the end of the stable energy region, which has led to a new ‘critical energy’ material property. Characterization of strain energy throughout the fatigue process has thus improved the understanding of an energy‐based fatigue life prediction method.
Evidence for high‐temperature in situ nifH transcription in an alkaline hot spring of Lower Geyser Basin, Yellowstone National Park
Authors: Loiacono Sara T. , Meyer‐Dombard D'Arcy R. , Havig Jeff R. , Poret‐Peterson Amisha T. , Hartnett Hilairy E. , Shock Everett L.
Published: March 2012

Genes encoding nitrogenase (nifH) were amplified from sediment and photosynthetic mat samples collected in the outflow channel of Mound Spring, an alkaline thermal feature in Yellowstone National Park. Results indicate the genetic capacity for nitrogen fixation over the entire range of temperatures sampled (57.2°C to 80.2°C). Amplification of environmental nifH transcripts revealed in situ expression of nifH genes at temperatures up to 72.7°C. However, we were unable to amplify transcripts of nifH at the higher‐temperature locations (> 72.7°C). These results indicate that microbes at the highest temperature sites contain the genetic capacity to fix nitrogen, yet either do not express nifH or do so only transiently. Field measurements of nitrate and ammonium show fixed nitrogen limitation as temperature decreases along the outflow channel, suggesting nifH expression in response to the downstream decrease in bioavailable nitrogen. Nitrogen stable isotope values of Mound Spring sediment communities further support geochemical and genetic data. DNA and cDNA nifH amplicons form several unique phylogenetic clades, some of which appear to represent novel nifH sequences in both photosynthetic and chemosynthetic microbial communities. This is the first report of in situ nifH expression in strictly chemosynthetic zones of terrestrial (non‐marine) hydrothermal systems, and sets a new upper temperature limit (72.7°C) for nitrogen fixation in alkaline, terrestrial hydrothermal environments.
Comparison of liraglutide versus other incretin‐related anti‐hyperglycaemic agents
Authors: Blonde L. , Montanya E.
Published: March 2012

The two classes of incretin‐related therapies, dipeptidyl peptidase‐4 (DPP‐4) inhibitors and glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), have become important treatment options for patients with type 2 diabetes. Sitagliptin, saxagliptin, vildagliptin and linagliptin, the available DPP‐4 inhibitors, are oral medications, whereas the GLP‐1 RAs—twice‐daily exenatide, once‐weekly exenatide and once‐daily liraglutide—are administered subcutaneously. By influencing levels of GLP‐1 receptor stimulation, these medications lower plasma glucose levels in a glucose‐dependent manner with low risk of hypoglycaemia, affecting postprandial plasma glucose more than most other anti‐hyperglycaemic medications. Use of GLP‐1 RAs has been shown to result in greater glycaemic improvements than DPP‐4 inhibitors, probably because of higher levels of GLP‐1 receptor activation. GLP‐1 RAs can also produce significant weight loss and may reduce blood pressure and have beneficial effects on other cardiovascular risk factors. Although both classes are well tolerated, DPP‐4 inhibitors may be associated with infections and headaches, whereas GLP‐1 RAs are often associated with gastrointestinal disorders, primarily nausea. Pancreatitis has been reported with both DPP‐4 inhibitors and GLP‐1 RAs, but a causal relationship between use of incretin‐based therapies and pancreatitis has not been established. In clinical trials, liraglutide has shown efficacy and tolerability and resulted in certain significant benefits when compared with exenatide and sitagliptin.
Unclassified renal cell carcinoma: a report of 56 cases
Authors: Lopez‐Beltran Antonio , Kirkali Ziya , Montironi Rodolfo , Blanca Ana , Algaba Ferran , Scarpelli Marina , Yorukoglu Kutsal , Hartmann Arndt , Cheng Liang
Published: March 2012

Study Type – Therapy (case series)

Level of Evidence 4

What's known on the subject? and What does the study add?

Unclassified RCC represents 0.7–5.7% of renal tumours. Limited reported data from two series suggests that unclassified RCC is an aggressive form of RCC, mainly because most cases are at an advanced stage at presentation, but overall and cancer‐specific survival were not significantly different between unclassified and clear‐cell RCC in an additional series of 38 patients.

Our study of 56 cases of unclassified RCC describes the pathological features that can be applied to predict prognosis on a daily basis. In particular nuclear grade, TNM classification, tumour coagulative necrosis, tumour size, microvascular invasion and 2004 WHO histotype are independent predictors of disease‐free and cancer‐specific survival.

OBJECTIVE

To evaluate the clinicopathological features and outcomes of 56 patients with unclassified renal cell carcinoma (RCC) meeting 2004 World Health Organization diagnostic criteria.

PATIENTS AND METHODS

Urological pathology files of the participating institutions were reviewed and cases of unclassified RCC that met the inclusion criteria were retrieved.

Nuclear grade, pT status, tumour size, regional lymph node involvement, distant metastases, coagulative tumour necrosis, mucin and sarcomatoid differentiation were evaluated in radical nephrectomy or nephron‐sparing specimens.

Significant factors in univariate analysis were then assessed by a multivariate analysis of independent prognostic factors using Cox proportional hazard regression analysis.

RESULTS

Fifty‐six cases met the histological criteria for unclassified RCC. Thirty‐four (61%) cases were categorized as unrecognizable cell type (mean overall survival 47 months; median 36 months), 20 (36%) as composites of recognized types (mean overall survival 36 months; median 26 months), and two (4%) (mean survival 16 months; median 16 months) as pure sarcomatoid morphology without recognizable epithelial elements.

Cox multivariate analysis showed nuclear grade (P= 0.020), stage (P < 0.001), tumour coagulative necrosis (P= 0.018), tumour size (P < 0.001), microvascular invasion (P < 0.001) and tumour histotype (P= 0.028) to be independent predictors of disease‐free survival, with tumour size being the most significant (hazard ratio [HR] 9.068, 95% confidence interval [CI] 3.231–25.453).

Nuclear grade (P= 0.026), stage (P < 0.001), tumour coagulative necrosis (P < 0.001), tumour size (P= 0.044), microvascular invasion (P < 0.001), tumour recurrence after surgery (P < 0.001) and tumour histotype (P= 0.056) were independent predictors of cancer‐specific survival, with tumour recurrence after surgery being the most significant (HR 14.713, 95% CI 5.329–40.622).

CONCLUSION

The prognosis of patients with unclassified RCC seems to be related to clinicopathological features known to be relevant in common forms of RCC.
Internationalism in a Divided World: The Experience of the International Federation of League of Nations Societies, 1919–1939
Authors: Davies Thomas R.
Published: March 2012

Despite the challenges of the geopolitical divisions of the interwar years, the International Federation of League of Nations Societies (IFLNS) brought together associations claiming to promote the ideals of the League of Nations in forty countries. It pioneered techniques for the lobbying of intergovernmental organizations that were so extensive that some considered it a “third chamber” of the League of Nations, and in areas such as its minorities work the Federation’s independent policy initiatives may be considered to be precursors to present‐day “politics beyond the state.” Based largely on hitherto neglected publications and archives of the IFLNS, this is the first article to evaluate specifically the work of a body that at the time was often considered to be the leading international nongovernmental organization for the promotion of peace between the world wars. The article introduces the evolution of the IFLNS and explores its national and international work in turn.
An altered redox balance mediates the hypersensitivity of Cockayne syndrome primary fibroblasts to oxidative stress
Authors: Pascucci Barbara , Lemma Tiziana , Iorio Egidio , Giovannini Sara , Vaz Bruno , Iavarone Ivano , Calcagnile Angelo , Narciso Laura , Degan Paolo , Podo Franca , Roginskya Vera , Janjic Bratislav M. , Van Houten Bennett , Stefanini Miria , Dogliotti Eugenia , D’Errico Mariarosaria
Published: March 2012

Cockayne syndrome (CS) is a rare hereditary multisystem disease characterized by neurological and development impairment, and premature aging. Cockayne syndrome cells are hypersensitive to oxidative stress, but the molecular mechanisms involved remain unresolved. Here we provide the first evidence that primary fibroblasts derived from patients with CS‐A and CS‐B present an altered redox balance with increased steady‐state levels of intracellular reactive oxygen species (ROS) and basal and induced DNA oxidative damage, loss of the mitochondrial membrane potential, and a significant decrease in the rate of basal oxidative phosphorylation. The Na/K‐ATPase, a relevant target of oxidative stress, is also affected with reduced transcription in CS fibroblasts and normal protein levels restored upon complementation with wild‐type genes. High‐resolution magnetic resonance spectroscopy revealed a significantly perturbed metabolic profile in CS‐A and CS‐B primary fibroblasts compared with normal cells in agreement with increased oxidative stress and alterations in cell bioenergetics. The affected processes include oxidative metabolism, glycolysis, choline phospholipid metabolism, and osmoregulation. The alterations in intracellular ROS content, oxidative DNA damage, and metabolic profile were partially rescued by the addition of an antioxidant in the culture medium suggesting that the continuous oxidative stress that characterizes CS cells plays a causative role in the underlying pathophysiology. The changes of oxidative and energy metabolism offer a clue for the clinical features of patients with CS and provide novel tools valuable for both diagnosis and therapy.
Effects of trampling of a wet dairy pasture soil on soil porosity and on mitigation of nitrous oxide emissions by a nitrification inhibitor, dicyandiamide
Authors: Ball B. C. , Cameron K. C. , Di H. J. , Moore S.
Published: March 2012

Urine patches in dairy pastures are major sources of nitrous oxide (N2O). Wet winters result in compaction damage to pastures because of animal trampling. The nitrification inhibitor, dicyandiamide (DCD), is effective at reducing N2O emissions from urine patches. Here, we assessed the extent of damage to the physical quality of the soil by trampling and whether this influenced the ability of DCD to mitigate N2O emissions. A field experiment was conducted where a sandy loam soil was trampled by a mechanical hoof just before urine and DCD application. Trampling reduced air permeability and pore continuity, but this had no effect on bulk density. Urine appeared to have contributed to pore collapse and blockage. Trampling increased average cumulative N2O emissions from 1.74 to 4.66% of urine‐N applied. This effect was attributed to increased water‐filled pore space, aggregate destruction and suppression of grass growth. DCD was highly effective in reducing N2O emissions, with the N2O emission factor of the urine‐N being decreased by 58–63%. Trampling did not significantly affect the effectiveness of DCD in reducing N2O emissions.
Predicting the changes in environmentally and agronomically significant phosphorus forms following the cessation of phosphorus fertilizer applications to grassland
Authors: Dodd R. J. , Mcdowell R. W. , Condron L. M.
Published: March 2012

Phosphorus (P) loss from soil can impair surface water quality. Losses from soil are related to soil P concentrations, but agronomic measures such as Olsen P do not in many cases predict the potential for P loss. One possible strategy to decrease P loss is to stop applying P fertilizers. We examined the changes in both agronomic (Olsen P) and environmental [water‐extractable P (WEP) and calcium chloride‐extractable P (CaCl2‐P)] P tests, and the potential implications following a halt to P fertilizer application to four long‐term grassland field trials on different soil types. Exponential decreases in Olsen P and WEP concentration over time were observed in three of the four trials, but only in one trial for CaCl2‐P. The rates of decrease in Olsen P (OP) and WEP concentration were best correlated with initial WEP (WEPi) concentration and the quotient of Olsen Pi/P retention (PR, a measure of Al‐ and Fe‐oxides), respectively. The equation t = 1/(−0.035 × ln OPi/PR − 0.0455) × (ln WEPt − ln WEPi) was used to predict the time (t) taken for WEP concentrations at the sites to decrease to 0.02 mg/L (WEPt), which is proposed as a limit for dissolved reactive phosphorus in overland flow, and the result was 23–44 yr. Results from a similar equation for Olsen P predicted a quicker rate of WEP. A significant decline in dry matter (DM) yield was observed at one trial site. For this site, the rate of decline in DM yield was of a similar magnitude to the rate of decline in WEP concentration. This suggests that halting P fertilizer application to decrease P loss as measured by WEP concentration may decrease farm productivity. An alternative, more financially acceptable, strategy is required, such as a negative P balance while maintaining yields with N fertilizer, but further work is required to assess both the agronomic and environmental implications of this strategy.
Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans
Authors: Hysek CM , Schmid Y , Rickli A , Simmler LD , Donzelli M , Grouzmann E , Liechti ME
Published: March 2012

BACKGROUND AND PURPOSE The use of ±3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is associated with cardiovascular complications and hyperthermia.

EXPERIMENTAL APPROACH We assessed the effects of the α1‐ and β‐adrenoceptor antagonist carvedilol on the cardiostimulant, thermogenic and subjective responses to MDMA in 16 healthy subjects. Carvedilol (50 mg) or placebo was administered 1 h before MDMA (125 mg) or placebo using a randomized, double‐blind, placebo‐controlled, four‐period crossover design.

KEY RESULTS Carvedilol reduced MDMA‐induced elevations in blood pressure, heart rate and body temperature. Carvedilol did not affect the subjective effects of MDMA including MDMA‐induced good drug effects, drug high, drug liking, stimulation or adverse effects. Carvedilol did not alter the plasma exposure to MDMA.

CONCLUSIONS AND IMPLICATIONS α1‐ and β‐Adrenoceptors contribute to the cardiostimulant and thermogenic effects of MDMA in humans but not to its psychotropic effects. Carvedilol could be useful in the treatment of cardiovascular and hyperthermic complications associated with ecstasy use.
Postured like a whore? Misreading Hermione's statue
Authors: LANGLEY ERIC
Published: March 2012

This article responds to Harold Bloom's call to ‘read for the clinamen’– an author's creative misprision of, or characteristic divergence from, the work of a literary antecedent – offering an account of Shakespeare's deviation from a number of influential or source texts in his The Winter's Tale. From Ovid's tale of Pygmalion to Marston's Metamorphosis of Pigmalion's Image; from Greene's Pandosto to Aretino's Sixteen Postures, I demonstrate how Shakespeare evokes then revokes these precursory texts, swerving from the potentially malign influence of his predecessors. Discussion concludes in analysis of the critical and intertextual over‐determination of the statue scene.
Serologic Evidence that Ascaris and Toxoplasma Infections Impact Inflammatory Responses to Helicobacter pylori in Colombians
Authors: Ek Courtney , Whary Mark T. , Ihrig Melanie , Bravo Luis E. , Correa Pelayo , Fox James G.
Published: March 2012

Background:  Helicobacter pylori‐infected children from coastal Tumaco, Colombia, have more parasitism, and adults have lower gastric cancer risk compared with high‐altitude Pasto/Tuquerres residents. Because helminth and Toxoplasma gondii infections alter helicobacter gastritis in rodent models, we determined whether seropositivity to Ascaris lumbricoides or T. gondii was associated with Th2‐IgG1 or Th1‐IgG2 responses to H. pylori.

Methods:  Sera (240) from the two populations were evaluated for A. lumbricoides and T. gondii seropositivity and results correlated with IgE and IgG isotype responses to H. pylori.

Results:  Most Tumaco children and adults were seropositive for A. lumbricoides (89%, 66%), T. gondii (59%, 98%), or both (45%, 66%). In contrast, seropositivity among Pasto/Tuquerres children was much lower (9%A. lumbricoides, 11%T. gondii, and 2% dual positive) but increased in adults (58%A. lumbricoides, 82%T. gondii, and 41% dual positive). A. lumbricoides seropositivity correlated with elevated IgE and anti‐inflammatory Th2‐IgG1 responses to H. pylori, while T. gondiigondii seropositivity was linked to elevated IgE, pro‐inflammatory Th1‐IgG2, IgG3, and IgG4 responses to H. pylori. Individuals with high T. gondii titers had reduced Th1‐IgG2, IgG3, and IgG4 responses to H. pylori.

Conclusions:  Results support regional differences for childhood parasitism and indicate A. lumbricoides and T. gondii infections may impact inflammatory responses to H. pylori and partially explain differences in gastric cancer risk in Colombia.
Effects of Cholesterol on Helicobacter pylori Growth and Virulence Properties In Vitro
Authors: Jiménez‐Soto Luisa F. , Rohrer Stefanie , Jain Utkarsh , Ertl Claudia , Sewald Xaver , Haas Rainer
Published: March 2012

Background:  Colonization of the gastric mucosa by Helicobacter pylori is often associated with chronic gastric pathologies in humans. Development of disease correlates with the presence of distinct bacterial pathogenicity factors, such as the cag type IV secretion system (cag‐T4SS), the vacuolating cytotoxin (VacA), or the ability of the bacteria to acquire and incorporate cholesterol from human tissue.

Materials and Methods:  The in vitro growth of H. pylori requires media (Brucella broth) complemented with vitamins and horse serum or cyclodextrins, prepared as blood agar plates or liquid cultures. Liquid cultures usually show a slow growth. Here, we describe the successful growth of H. pylori strains 26695, P217, P12, and 60190 on serum‐free media replacing serum components or cyclodextrins with a commercially available cholesterol solution.

Results:  The effects of cholesterol as a substitute for serum or cyclodextrin were rigorously tested for growth of H. pylori on agar plates in vitro, for its general effects on bacterial protein synthesis (the proteome level), for H. pylori’s natural competence and plasmid DNA transfer, for the production of VacA, and the general function of the cag‐pathogenicity island and its encoded cag‐T4SS. Generally, growth of H. pylori with cholesterol instead of serum supplementation did not reveal any restrictions in the physiology and functionality of the bacteria except for strain 26695 showing a reduced growth on cholesterol media, whereas strain 60190 grew more efficient in cholesterol‐ versus serum‐supplemented liquid medium.

Conclusions:  The use of cholesterol represents a considerable option to serum complementation of growth media for in vitro growth of H. pylori.
p27kip1 Upregulated by hnRNPC1/2 Antagonizes CagA (a Virulence Factor of Helicobacter pylori)‐Mediated Pathogenesis
Authors: Jin Shenghang , Wu Minjin , Cao Hanqin , Ying Sunke , Hua Jiping , Chen Yu
Published: March 2012

Background and Aims:  Infection by Helicobacter pylori is one of the major contributing factors of chronic active gastritis and peptic ulcer and is closely associated with the occurrence and progression of gastric cancer. CagA protein is a major virulence factor of H. pylori that interacts with SHP‐2, a true oncogene, to interfere with cellular signaling pathways; CagA also plays a crucial role in promoting the carcinogenesis of gastric epithelial cells. However, currently, the molecular mechanisms of gastric epithelial cells that antagonize CagA pathogenesis remain inconclusive.

Methods:  We showed that AGS gastric cancer cells transfected with CagA exhibited the inhibition of proliferation and increased activity of caspase 3/7 using two‐dimensional gel electrophoresis and secondary mass spectrometry (MS/MS).

Results:  It was found that the AGS gastric cancer cells stably expressing CagA displayed significantly increased the expression of 16 proteins, including hnRNPC1/2. Further analysis revealed that hnRNPC1/2 significantly boosted the expression of the p27kip1 protein.

Conclusion: Our data suggested that hnRNPC1/2 upregulates p27kip1 expression and the subsequent suppression of cell proliferation and induction of apoptosis, thereby providing an important mechanism whereby gastric epithelial cells antagonize CagA‐mediated pathogenesis.
Chronic Daily Headache in U.S. Soldiers After Concussion
Authors: Theeler Brett J. , Flynn Frederick G. , Erickson Jay C.
Published: March 2012

(Headache 2012;52:732‐738)

Objective.— To determine the prevalence and characteristics of, and factors associated with, chronic daily headache (CDH) in U.S. soldiers after a deployment‐related concussion.

Methods.— A cross‐sectional, questionnaire‐based study was conducted with a cohort of 978 U.S. soldiers who screened positive for a deployment‐related concussion upon returning from Iraq or Afghanistan. All soldiers underwent a clinical evaluation at the Madigan Traumatic Brain Injury Program that included a history, physical examination, 13‐item self‐administered headache questionnaire, and a battery of cognitive and psychological assessments. Soldiers with CDH, defined as headaches occurring on 15 or more days per month for the previous 3 months, were compared to soldiers with episodic headaches occurring less than 15 days per month.

Results.— One hundred ninety‐six of 978 soldiers (20%) with a history of deployment‐related concussion met criteria for CDH and 761 (78%) had episodic headache. Soldiers with CDH had a median of 27 headache days per month, and 46/196 (23%) reported headaches occurring every day. One hundred seven out of 196 (55%) soldiers with CDH had onset of headaches within 1 week of head trauma and thereby met the time criterion for posttraumatic headache (PTHA) compared to 253/761 (33%) soldiers with episodic headache. Ninety‐seven out of 196 (49%) soldiers with CDH used abortive medications to treat headache on 15 or more days per month for the previous 3 months. One hundred thirty out of 196 (66%) soldiers with CDH had headaches meeting criteria for migraine compared to 49% of soldiers with episodic headache. The number of concussions, blast exposures, and concussions with loss of consciousness was not significantly different between soldiers with and without CDH. Cognitive performance was also similar for soldiers with and without CDH. Soldiers with CDH had significantly higher average scores on the posttraumatic stress disorder (PTSD) checklist compared to soldiers with episodic headaches. Forty‐one percent of soldiers with CDH screened positive for PTSD compared to only 18% of soldiers with episodic headache.

Conclusions.— The prevalence of CDH in returning U.S. soldiers after a deployment‐related concussion is 20%, or 4‐ to 5‐fold higher than that seen in the general U.S. population. CDH following a concussion usually resembles chronic migraine and is associated with onset of headaches within the first week after concussion. The mechanism and number of concussions are not specifically associated with CDH as compared to episodic headache. In contrast, PTSD symptoms are strongly associated with CDH, suggesting that traumatic stress may be an important mediator of headache chronification. These findings justify future studies examining strategies to prevent and treat CDH in military service members following a concussive injury.
Rapid Decline of Liver Stiffness Following Alcohol Withdrawal in Heavy Drinkers
Authors: Trabut Jean‐Baptiste , Thépot Véronique , Nalpas Bertrand , Lavielle Béatrice , Cosconea Simona , Corouge Marion , Vallet‐Pichard Anaïs , Fontaine Hélène , Mallet Vincent , Sogni Philippe , Pol Stanislas
Published: March 2012

Background:

Measurement of liver stiffness (LS) using real‐time elastography appears as a promising tool to evaluate the severity of chronic liver diseases. Previous studies in patients with alcoholic liver disease have suggested that fibrosis was the only histological parameter to influence LS. To challenge this hypothesis, we have prospectively tested the short‐term impact of alcohol withdrawal on LS value.

Methods:

Patients hospitalized for alcohol withdrawal in our Liver and Addiction Unit between 2007 and 2010 had an LS determination at entry (D0) and 7 days after alcohol withdrawal (D7). LS value was given as the median of 10 measurements performed with a FibroScan® device. For a given patient, variation of LS was considered as significant when the comparison of the 10 measurements at D0 and at D7 yielded a p‐value under 0.05 (Wilcoxon test).

Results:

One hundred and thirty‐seven patients were included in the study (median alcohol consumption: 150 g/d; hepatitis C: n = 21 [15.6%]). Considering all patients, median LS value decreased from 7.2 to 6.1 kPa between D0 and D7 (p = 0.00001, paired Wilcoxon test). LS decreased significantly in 62 patients (45.3%), and there was a reduction in the estimated stage of fibrosis in 32 (23.3%). LS increased significantly in 16 patients (11.7%). Subgroup analyses revealed that the decrease in LS was still significant in patients with or without hepatitis C infection, and aspartate transaminase level below or above 100 UI/l.

Conclusions:

LS decreases significantly in nearly half of heavy drinkers after only 7 days of abstinence. This result strongly suggests that nonfibrotic lesions (such as the presence of alcoholic hepatitis) may influence LS. From a practical point of view, it also shows that variation of alcohol consumption must be taken into account for the interpretation of LS value.