bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased risk of sudden unexpected death in epilepsy in females using lamotrigine: A nested, case‐control study
Authors: Aurlien Dag , Larsen Jan Petter , Gjerstad Leif , Taubøll Erik 
Published: December 2011

SummaryPurpose:  To estimate the incidence of sudden unexpected death in epilepsy (SUDEP) in Rogaland County, Norway, in the period August 1 1995–July 31 2005, and to investigate whether use of lamotrigine (LTG) was associated with increased risk in female patients or other subgroups.Methods:  SUDEP victims were identified from autopsy reports and data from the Norwegian Cause of Death Registry. In all cases where SUDEP was considered as a possible cause of death, the hospital records were also reviewed. For each deceased, at least three living patients with epilepsy were randomly selected as controls. The market share in defined daily doses was collected for each year to estimate the number of patient‐years at risk on each antiepileptic drug.Key Findings:  We identified 26 cases of SUDEP: 16 definite, 3 probable, and 7 possible; 15 patients were female and 11 were male. Of these, 10 patients (38.5%) were treated with LTG: 9 of these patients were female. The incidence of SUDEP was estimated as 1.0 per 1,000 patient‐years when all cases were included, and 0.7 per 1,000 patient‐years for definite and probable SUDEP. Seven of 12 (58.3%) of female patients with definite and probable SUDEP and 10 of 41 (24.4%) of controls matched on age and gender were on LTG (p = 0.038). The incidence of definite and probable SUDEP in women on LTG, was estimated as 2.5 per 1,000 patient‐years and 0.5 per 1,000 patient‐years in female who were not taking LTG (p = 0.007).Significance:  The incidence of SUDEP was significantly higher among female patients with epilepsy who were being treated with LTG than among female patients with epilepsy who were not taking LTG, and a significantly higher proportion of female SUDEP cases than controls were taking LTG. Our findings may have implications for treatment of epilepsy in female patients.
Mild hypoxia‐induced cardiomyocyte hypertrophy via up‐regulation of HIF‐1α‐mediated TRPC signalling
Authors: Chu Wenfeng , Wan Lin , Zhao Dan , Qu Xuefeng , Cai Fulai , Huo Rong , Wang Ning , Zhu Jiuxin , Zhang Chun , Zheng Fangfang , Cai Ruijun , Dong Deli , Lu Yanjie , Yang Baofeng 
Published: December 2011

AbstractHypoxia‐inducible factor‐1 alpha (HIF‐1α) is a central transcriptional regulator of hypoxic response. The present study was designed to investigate the role of HIF‐1α in mild hypoxia‐induced cardiomyocytes hypertrophy and its underlying mechanism. Mild hypoxia (MH, 10% O2) caused hypertrophy in cultured neonatal rat cardiac myocytes, which was accompanied with increase of HIF‐1α mRNA and accumulation of HIF‐1α protein in nuclei. Transient receptor potential canonical (TRPC) channels including TRPC3 and TRPC6, except for TRPC1, were increased, and Ca2+‐calcineurin signals were also enhanced in a time‐dependent manner under MH condition. MH‐induced cardiomyocytes hypertrophy, TRPC up‐regulation and enhanced Ca2+‐calcineurin signals were inhibited by an HIF‐1α specific blocker, SC205346 (30 μM), whereas promoted by HIF‐1α overexpression. Electrophysiological voltage‐clamp demonstrated that DAG analogue, OAG (30 μM), induced TRPC current by as much as 170% in neonatal rat cardiomyocytes overexpressing HIF‐1α compared to negative control. These results implicate that HIF‐1α plays a key role in development of cardiac hypertrophy in responses to hypoxic stress. Its mechanism is associated with up‐regulating TRPC3, TRPC6 expression, activating TRPC current and subsequently leading to enhanced Ca2+‐calcineurin signals.
Prognostic value of PINI index in patients with multiple myeloma
Authors: Dupire Sophie , Wemeau Mathieu , Debarri Houria , Pascal Laurent , Hivert Benedicte , Willekens Christophe , Boyle Eileen , Manier Salomon , Béatrice Thielemans , Onraed Brigitte , Faucompré Jean‐Luc , Hennache Bernadette , Dumontet Charles , Facon Thierry , Leleu Xavier 
Published: December 2011

AbstractBackground:  The Prognostic Inflammatory and Nutritional Index (PINI) is a simple scoring system that aggregates two blood markers of inflammatory [C‐reactive protein (CRP) and orosomucoid] and of nutritional (albumin and prealbumin) states. It is used in routine practice in geriatric medicine, especially in hospitalized elderly patients. This study was undertaken to evaluate the usefulness of PINI index in multiple myeloma (MM), a malignancy of the elderly.Method:  The PINI score was determined in 231 previously untreated patients with MM, of whom 112 were ≥65 yrs old. The serum albumin, prealbumin, orosomucoid (human α1‐acid glycoprotein), and hsCRP are measured routinely by immunonephelometry.Results:  In the overall population and the elderly subset, PINI ≥ 4 (‘high PINI’) was correlated with a shorter median survival, 26 vs. 65 months in the high and low PINI groups, respectively. The prognostic impact of PINI index was dramatic in the elderly MM subgroup, 6 and 45 months, respectively. The high PINI index also predicted for shorter survival in various groups with good prognostic, such as low International Staging System (ISS) stages, low b2m, and absence of del17p and t(4;14), further demonstrating its prognostic impact on overall survival. In multivariate analysis, PINI index provided additional survival prognostic information to b2m in a b2m/PINI model.Conclusion:  PINI index appears to be a useful and easy‐to‐perform marker in routine to determine the prognosis of patients with MM, especially in the elderly population. PINI might represent an alternative to ISS score, especially in elderly patients, in the future.
Interactive effects of global warming and ‘global worming’ on the initial establishment of native and exotic herbaceous plant species
Authors: Eisenhauer Nico , Fisichelli Nicholas A. , Frelich Lee E. , Reich Peter B. 
Published: December 2011

The spread of exotic earthworms (‘worming’) and rising temperatures are expected to alter the biological, chemical and physical properties of many ecosystems, yet little is known about their potential interactive effects. We performed a laboratory microcosm experiment to investigate the effects of earthworms (anecic, endogeic, epigeic, or all three together) and 4°C warming on soil water content, litter turnover and seedling establishment of four native and four exotic herbaceous plant species.Warming and worming exerted independent as well as interactive effects on soil processes and plant dynamics. Warming reduced the water content of the upper soil layer, but only in the presence of earthworms. Litter removal increased in the presence of earthworms, the effect being most pronounced in the presence of anecic earthworms at ambient temperature. Exotic plant species were most influenced by earthworms (lower seedling number but higher biomass), whereas natives were most sensitive to warming (higher seedling number). This differential response resulted in significant interaction effects of earthworms and warming on abundance and richness of native relative to exotic plants as well as related shifts in plant species composition. Structural equation modeling allowed us to address possible mechanisms: direct effects of earthworms primarily affected exotic plants, whereas earthworms and warming indirectly and differentially affected native and exotic plants through changes in soil water content and surface litter.Invasive earthworms and warming are likely to interactively impact abiotic and biotic ecosystem properties. The invasion of epigeic and anecic species could select for plant species able to germinate on bare soil and tolerate drought, with the latter becoming more important in a warmer world. Thus earthworm invasion may result in simplified plant communities of increased susceptibility to the invasion of exotic plants.
Serum cytokine levels and periodontal parameters in ankylosing spondylitis
Authors: Sezer U. , Erciyas K. , Pehlivan Y. , Üstün K. , Tarakçıoğlu M. , Şenyurt S. Z. , Onat A. M. 
Published: December 2011

Sezer U, Erciyas K, Pehlivan Y, Üstün K, Tarakçıoğlu M, Şenyurt SZ, Onat AM. Serum cytokine levels and periodontal parameters in ankylosing spondylitis. J Periodont Res 2012; 47: 396–401. © 2011 John Wiley & Sons A/SBackground and Objective:  Multiple studies support the role of periodontal disease in contributing to the chronic systemic inflammatory burden in a variety of diseases, including ankylosing spondylitis (AS), in the progression which the inflammatory process plays an important role. We assume that patients with AS are more likely to have periodontal disease than healthy individuals. The aim of this study was to determine the possible relationship between inflammatory periodontal diseases and AS by evaluating clinical periodontal parameters and serum cytokine levels.Material and Methods:  Forty‐eight adults with AS (35 women and 13 men; age range 18–56 years; mean age 34.27 years) and 48 age‐ and sex‐matched systemically healthy control subjects participated in the study. The clinical periodontal parameters, venous blood and Bath Ankylosing Spondylitis Disease Activity Score were obtained, and serum C‐reactive protein, tumour necrosis factor‐α and interleukin‐6 (IL‐6) levels were evaluated.Results:  There was statistically no significant difference in the frequency of periodontitis between AS patients and the control group. Furthermore, there was no significant difference in probing depth, clinical attachment level and plaque index, and the only significant clinical difference between groups was in levels of bleeding on probing (p < 0.001). Serum concentrations of IL‐6, tumour necrosis factor‐α and C‐reactive protein in the AS group were significantly higher than those in the control group (p < 0.001). In the AS group, there was a correlation between serum IL‐6 levels and clinical attachment level (p < 0.001).Conclusion:  The results of present study suggest that bleeding on probing was the only different periodontal parameter between the AS and the control group, and the periodontal status of patients with AS may be affected by IL‐6 levels.
Sulfide‐ and nitrite‐dependent nitric oxide production in the intestinal tract
Authors: Vermeiren Joan , Van de Wiele Tom , Van Nieuwenhuyse Glynn , Boeckx Pascal , Verstraete Willy , Boon Nico 
Published: December 2011

SummaryIn the gut ecosystem, nitric oxide (NO) has been described to have damaging effects on the energy metabolism of colonocytes. Described mechanisms of NO production are microbial reduction of nitrate via nitrite to NO and conversion of l‐arginine by NO synthase. The aim of this study was to investigate whether dietary compounds can stimulate the production of NO by representative cultures of the human intestinal microbiota and whether this correlates to other processes in the intestinal tract. We have found that the addition of a reduced sulfur compound, i.e. cysteine, contributed to NO formation. This increase was ascribed to higher sulfide concentrations generated from cysteine that in turn promoted the chemical conversion of nitrite to NO. The NO release from nitrite was of the order of 4‰ at most. Overall, it was shown that two independent biological processes contribute to the chemical formation of NO in the intestinal tract: (i) the production of sulfide by fermentation of sulfur containing amino acids or reduction of sulfate by sulfate reducing bacteria, and (ii) the reduction of nitrate to nitrite. Our results indicate that dietary thiol compounds in combination with nitrate may contribute to colonocytes damaging processes by promoting NO formation.
Behcet’s disease: is there a gender influence on clinical manifestations?
Authors: DAVATCHI Fereydoun , SHAHRAM Farhad , CHAMS‐DAVATCHI Cheyda , SADEGHI ABDOLLAHI Bahar , SHAMS Hormoz , NADJI Abdolhadi , FAEZI Tahereh , AKHLAGHI Massoomeh , GHODSI Zahra , LARIMI Roghieh , ASHOFTEH Farima 
Published: December 2011

AbstractAim:  In Behcet’s disease (BD), it is customary to believe that men are more affected than women, major organs are more involved in men, and they have worse outcomes. The male‐to‐female ratio is reported from 5.37 to 1 (Egypt), to 0.38 to 1 (US). If in the majority of reports BD was seen more frequently in men, in some others it was more frequent in women. The aim of this study was to examine a large cohort of patients, in whom manifestations were gender related, and to examine the strength of associations and their clinical relevance.Patients and Methods:  All patients of the BD registry, Rheumatology Research Center, Tehran University of Medical Sciences, entered the study (6702 patients). The percentage of 95 items was calculated in both genders (with their 95% confidence intervals), and were compared together by the chi‐squared test. Odds ratio (OR) and relative risk (RR) were also calculated.Results:  Forty‐three out of 95 items were gender‐related (29 for males, 14 for females) with a statistically significant difference by chi‐squared. Significant OR (confidence interval not reaching 1) was found for 79 items. However, clinically significant OR (2 or more for men and 0.5 or less for women) showed an association only with 16 items; five with females and 11 with males. The most important was vascular involvement.Conclusion:  No strong association (OR of 2 or more) was found between the male gender and major organ involvement, except for vascular lesions.
Clinical evaluation of non‐carious cervical lesion restorations using a HEMA‐free adhesive: three‐year results
Authors: Burrow MF 
Published: December 2011

AbstractBackground:  The use of all‐in‐one resin‐based adhesives in clinical practice has continued to increase. The aim of this study was to evaluate retention and marginal staining of a HEMA‐free all‐in‐one adhesive Go! (SDI, Australia) and Ice resin composite in non‐carious cervical lesions (NCCLs).Methods:  Forty‐one restorations were placed in 13 patients (age range 44–72 years). Human Ethics Committee approval from the University of Melbourne and Dental Health Services Victoria was obtained. Restorations were bonded and placed according to the manufacturer’s instructions. Enamel etching was performed on NCCL margins after cleaning with pumice and water. Patients were recalled at six months and one, two and three years. Restorations were evaluated for retention and marginal staining, and photographic records of restorations were obtained.Results:  At three years, six patients were available for recall with 23 restoration sites reviewed. At the six‐month recall, three restorations had been lost, with a further two lost at two years. At three years, an overall cumulative retention rate of 85% was calculated using survival analysis. Fifteen of the 23 restorations showed slight marginal staining.Conclusions:  At three years, the overall retention rate of 85% indicates a satisfactory result for this new adhesive. Marginal staining was regarded as minimal.
Loss of the 14-3-3σ Tumor Suppressor Is a Critical Event in ErbB2-Mediated Tumor Progression
Authors: Ling Chen , Su Vi-Minh-Tri , Zuo Dongmei , Muller William J. 
Published: December 2011

Abstract
14-3-3σ is a putative tumor suppressor involved in cell-cycle progression and epithelial polarity. We demonstrate that loss of one or both copies of the conditional 14-3-3σ allele results in accelerated mammary and salivary tumorigenesis in mice expressing an activated erbB2 oncogene under the endogenous erbB2 promoter. Significantly, the majority of tumors bearing a single conditional 14-3-3σ allele lose expression of the remaining 14-3-3σ allele, which is associated with epigenetic methylation of the 14-3-3σ locus. In addition to accelerated tumor onset, in a mouse mammary tumor virus-driven ErbB2 tumor model, loss of 14-3-3σ results in enhanced metastatic phenotype that is correlated with loss of cellular junctions. Taken together, these results provide compelling evidence that 14-3-3σ is a potent tumor suppressor involved in ErbB2-driven breast cancer initiation and metastasis.
Significance: 14-3-3σ has been identified as a normal mammary epithelial cell marker frequently downregulated during neoplastic development. Consistent with its potential role as a tumor suppressor, we demonstrate that targeted disruption of 14-3-3σ in a number of epithelial tissues can profoundly impact both the initiation and metastatic phases of ErbB2-mediated tumor progression through modulation of a number of distinct signaling networks. Cancer Discovery; 2(1); 68–81. ©2011 AACR.
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PI3Kδ Inhibitors in Cancer: Rationale and Serendipity Merge in the Clinic
Authors: Fruman David A. , Rommel Christian 
Published: December 2011

AbstractSeveral phosphoinositide 3-kinase (PI3K) inhibitors are in the clinic and many more are in preclinical development. CAL-101, a selective inhibitor of the PI3Kδ isoform, has shown remarkable success in certain hematologic malignancies. Although PI3Kδ signaling plays a central role in lymphocyte biology, the degree of single-agent therapeutic activity of CAL-101 during early-phase development has been somewhat unexpected. CAL-101 works in part by blocking signals from the microenvironment that normally sustain leukemia and lymphoma cells in a protective niche. As PI3Ks enter the arena of molecular-targeted therapies, CAL-101 provides proof of principle that isoform-selective compounds can be effective in selected cancer types and patient populations.Significance: A key question is whether compounds targeting a single PI3K catalytic isoform can provide meaningful single agent efficacy in cancer cells that express multiple isoforms. Clinical studies of the drug CAL-101 have provided a significant advance by showing that selective targeting of PI3Kδ achieves efficacy in chronic lymphocytic leukemia, in part through targeting the tumor microenvironment. Cancer Discovery; 1(7); 562–72. ©2011 AACR.
Associations Between Lipoprotein(a) Levels and Cardiovascular Outcomes in Black and White Subjects
Authors: Virani Salim S. , Brautbar Ariel , Davis Brian C. , Nambi Vijay , Hoogeveen Ron C. , Sharrett A. Richey , Coresh Josef , Mosley Thomas H. , Morrisett Joel D. , Catellier Diane J. , Folsom Aaron R. , Boerwinkle Eric , Ballantyne Christie M. 
Published: December 2011

Background—
On the basis of studies with limited statistical power, lipoprotein(a) [Lp(a)] is not considered a risk factor for cardiovascular disease (CVD) in blacks. We evaluated associations between Lp(a) and incident CVD events in blacks and whites in the Atherosclerosis Risk in Communities (ARIC) study.

Methods and Results—

Plasma Lp(a) was measured in blacks (n=3467) and whites (n=9851). Hazards ratios (HRs) for incident CVD events (coronary heart disease and ischemic strokes) were calculated. Lp(a) levels were higher with wider interindividual variation in blacks (median [interquartile range], 12.8 [7.1–21.7] mg/dL) than whites (4.3 [1.7–9.5] mg/dL;
P
<0.0001). At 20 years of follow-up, 676 CVD events occurred in blacks, and 1821 events occurred in whites. Adjusted HRs (95% confidence interval) per race-specific 1-SD–greater log-transformed Lp(a) were 1.13 (1.04–1.23) for incident CVD, 1.11 (1.00–1.22) for incident coronary heart disease, and 1.21 (1.06–1.39) for ischemic strokes in blacks. For whites, the respective HRs (95% confidence intervals) were 1.09 (1.04–1.15), 1.10 (1.05–1.16), and 1.07 (0.97–1.19). Quintile analyses showed that risk for incident CVD was graded but statistically significant only for the highest compared with the lowest quintile (HR [95% confidence interval], 1.35 [1.06–1.74] for blacks and 1.27 [1.10–1.47] for whites). Similar results were obtained with the use of Lp(a) cutoffs of ≤10 mg/dL, >10 to ≤20 mg/dL, >20 to ≤30 mg/dL, and >30 mg/dL.

Conclusions—
Lp(a) levels were positively associated with CVD events. Associations were at least as strong, with a larger range of Lp(a) concentrations, in blacks compared with whites.
Advertising Regulation and the Protection of Children-Consumers in the European Union: In the Best Interests of ... Commercial Operators?
Authors: Garde Amandine 
Published: December 2011

AbstractThis article argues that, despite its promise to mainstream the best interests of the child into all EU policies, the European Commission has failed to ensure that the EU internal market and consumer policies, which are at the heart of the EU legal order, adequately protect children. Two main pieces of EU legislation illustrate the argument: the Unfair Commercial Practices Directive and the Audiovisual Media Services Directive.
The EU, Online Child Safety and Media Literacy
Authors: Savirimuthu Joseph 
Published: December 2011

AbstractMedia literacy continues to assume an important role in EU online child safety governance. Its central premise is that individuals who do not have access to relevant information will be least able to make informed choices about how online interactions and risks can be managed in safe and effective manner. This intuition is broadly correct but 'network publics' create new complications that media literacy measures must now address. This article examines the role of the EU in enhancing the safety of children in the online environment through the use of public awareness and education strategies. The analysis of EU online child safety governance strategy and, more specifically, the awareness-raising strategies pursued under the Safer Internet Programme reveals some of the ways child safety issues are now being transformed into legal and social obligations.
Fides publica in Ancient Rome and its reception by Grotius and Locke
Authors: de Wilde Marc 
Published: December 2011

AbstractThe article analyzes the Roman notion of des publica and its reception by Grotius and Locke. The Romans considered des publica a general standard of behavior for all those invested with state power. It was regarded as a legal norm with moral connotations, which applied especially, though not exclusively, to exceptional situations, such as wars. Grotius appears to have been the first since Antiquity to rediscover the notion of des publica as a fundamental norm of public law; for him, it became especially valuable as a criterion for determining the legality of civil war and resistance. This understanding of des was also adopted by Locke, who argued that the people had a right of resistance in case the government structurally violated its trust. Contrary to the dominant view in the literature, this article shows that Locke's concept of trust was influenced not only by peculiarly English ideas about political trusteeship, but also by the Roman notion of des publica.