bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Risk of Clostridium difficile Infections in Hospitalized Patients with Inflammatory Bowel Disease in a German Tertiary Referral Center
Authors: Ott Claudia , Girlich Christiane , Klebl Frank , Plentz Annelie , Iesalnieks Igors , Schölmerich Jürgen , Obermeier Florian
Published: June 2011

Introduction: Many reports, mainly from the US and Canada but also a recent report from a center in Europe, have documented the increasing impact of Clostridium difficile infections in patients with inflammatory bowel disease (IBD) during the last years. To determine the prevalence of C. difficile infections in hospitalized IBD patients in a tertiary referral center in Germany, we conducted this retrospective analysis. Methods: Data of all IBD in-patients treated due to an acute flare of their IBD at the Department of Internal Medicine I of the University of Regensburg between January 1, 2001, and June 30, 2008, were analyzed. In patients with a concomitant diagnosis of C. difficile infection, further variables such as IBD-related treatment at the time of infection or outcome were examined. Results: In total, 995 in-patients with IBD were treated in this hospital [638 patients with Crohn’s disease (CD), 357 with ulcerative colitis (UC)] during the study period. Of these, 279 patients with CD and 242 patients with UC were admitted with an acute flare and suffering from diarrhea and abdominal pain. Only 10 of those were diagnosed as having a concomitant infection with C. difficile. Six patients were female and the median age was 49 years (range: 15–80). Six patients with C. difficile infections suffered from UC and 4 patients from CD, all with previous colonic involvement. Eight patients used immunosuppressive therapies; only 2 patients were treated with antibiotics before infection. Conclusion: In contrast to recent reports from other countries, only a low percentage of hospitalized patients with acute flares of their IBD were identified as having an underlying C. difficile infection in this German tertiary referral center. However, in IBD patients with an acute flare, a concomitant C. difficile infection should be excluded, especially in patients with immunosuppressive treatment and colonic involvement of their disease. Further research is needed to evaluate if regions with different risks of C. difficile infections exist and to find out more about potential reasons for this observation.
Aging Is Associated with a Proapoptotic Endothelial Progenitor Cell Phenotype
Authors: Kushner Erich J. , MacEneaney Owen J. , Weil Brian R. , Greiner Jared J. , Stauffer Brian L. , DeSouza Christopher A.
Published: June 2011

The aim of this study was to determine if aging is associated with enhanced endothelial progenitor cell (EPC) sensitivity to apoptosis. Cells with phenotypic EPC characteristics were isolated from healthy, nonobese young (age 25 ± 1 years) and older (61 ± 1 years) men. Intracellular active caspase-3 concentrations in response to staurosporine stimulation were approximately 35% higher (p < 0.05) in EPCs from older (3.15 ± 0.29 pg/ml) compared with young (2.33 ± 0.24 pg/ml) men. Protein expression of Akt, p70 S6-kinase and Bcl-2 was markedly lower (approx. 35, 75 and 60%, respectively, all p < 0.05) in EPCs from older compared with young men, whereas there were no age-related differences in either 14-3-3Ε or Bax expression. Additionally, EPC telomerase activity was 57% lower (p < 0.05) in older (0.18 ± 0.11 AU) versus young (0.43 ± 0.11 AU) men. These results indicate that aging is associated with a proapoptotic EPC phenotype characterized by decreased expression of key antiapoptotic proteins associated with the PI-3-kinase signaling pathway and reduced telomerase activity. These age-related changes likely contribute, in part, to the diminished ability of EPCs to resist an apoptotic stimulus in older men. Increased susceptibility to apoptosis may contribute to the numerical and functional impairments observed in EPCs with aging.
Design of Erosion/Abrasion Studies – Insights and Rational Concepts
Authors: Wiegand Annette , Attin Thomas
Published: June 2011

In vitro and in situ studies modelling the wear of dental hard tissues due to erosion and abrasion are characterised by a high variation in study designs and experimental parameters. Based on a summary of the existing protocols, the present review aimed to describe and discuss the parameters which must be carefully considered in erosion-abrasion research, especially when it is intended to simulate clinical conditions. Experimental characteristics and parameters were retrieved from a total of 42 in vitro and 20 in situ studies. The key experimental characteristics included parameters of erosion (duration and pH) and abrasion (duration, kinds of toothbrush and toothpaste, brushing force, and time point) as well as co-factors (e.g. dental hard tissue). The majority of studies used models with alternating erosion/abrasion treatments intended to simulate clinical conditions, while other studies exaggerated clinical conditions intentionally, often using only a single erosion/abrasion treatment. Both in vitro and in situ models shared a high level of standardisation, but several studies showed a trend to severe erosion (e.g. >5 min/cycle) or extensive brushing (e.g. >100 brushing strokes/cycle) at a high frequency and repetition rate. Thus, studies often tend to produce a higher amount of wear than in the clinical situation, especially as modifying biological factors (e.g. the dilution of the erosive solution by saliva and the protective effect of the pellicle) cannot be simulated adequately. With respect to the existing models, it seems advisable to diminish duration and frequency of erosion and abrasion to more realistic clinical conditions when the everyday situation is to be simulated. Experimental parameters must be chosen with care to ensure that the problem is investigated in an appropriate mode at standardised conditions and with adequate measuring systems to allow prediction of clinical outcomes.
Clinical Studies of Dental Erosion and Erosive Wear
Authors: Huysmans M.C.D.N.J.M. , Chew H.P. , Ellwood R.P.
Published: June 2011

We define erosion as apartial demineralisation of enamel or dentine by intrinsic or extrinsic acidsand erosive tooth wear as the accelerated loss of dental hard tissue through the combined effect of erosion and mechanical wear (abrasion and attrition) on the tooth surface. Most experts believe that during the last decade there has been a significant increase in the prevalence and severity of erosive tooth wear, particularly in adolescents. Even when erosive wear occurs in its milder forms, this is a matter of concern, as it may compromise the integrity of an otherwise healthy dentition in later life. The erosive wear process is complicated and modified by many chemical, behavioural and associated processes in the mouth. If interventions are to be developed it is therefore important that in vivo methods are developed to assess the outcomes of the erosion and erosive wear processes and the effects of interventions upon them. This paper discusses potential methods of investigating erosion and erosive wear in vivo and the difficulties associated with clinical studies.
The Phonatory Deviation Diagram: A Novel Objective Measurement of Vocal Function
Authors: Madazio Glaucya , Leão Sylvia , Behlau Mara
Published: June 2011

Aim: To identify the discriminative characteristics of the phonatory deviation diagram (PDD) in rough, breathy and tense voices. Methods: One hundred and ninety-six samples of normal and dysphonic voices from adults were submitted to perceptual auditory evaluation, focusing on the predominant vocal quality and the degree of deviation. Acoustic analysis was performed with the VoxMetria (CTS Informatica). Results: Significant differences were observed between the dysphonic and normal groups (p < 0.001), and also between the breathy and rough samples (p = 0.044) and the breathy and tense samples (p < 0.001). All normal voices were positioned in the inferior left quadrant, 45% of the rough voices in the inferior right quadrant, 52.6% of the breathy voices in the superior right quadrant and 54.3% of the tense voices in the inferior left quadrant of the PDD. In the inferior left quadrant, 93.8% of voices with no deviation were located and 72.7% of voices with mild deviation; voices with moderate deviation were distributed in the inferior and superior right quadrants, the latter ones containing the most deviant voices and 80% of voices with severe deviation. Conclusion: The PDD was able to discriminate normal from dysphonic voices, and the distribution was related to the type and degree of voice alteration.
Role of Prostaglandin D Receptor CRTH2 in Sustained Eosinophil Accumulation in the Airways of Mice with Chronic Asthma
Authors: Kagawa Shizuko , Fukunaga Koichi , Oguma Tsuyoshi , Suzuki Yusuke , Shiomi Tetsuya , Sayama Koichi , Kimura Tokuhiro , Hirai Hiroyuki , Nagata Kinya , Nakamura Masataka , Asano Koichiro
Published: June 2011

The prostaglandin D2 (PGD2)/CRTH2 pathway is important for eosinophil trafficking in vitro; however, genetic deficiency of CRTH2 does not suppress in vivo eosinophilic airway inflammation in acute models of asthma, and the role of CRTH2 in the pathogenesis of asthma is still ambiguous. Therefore, in the present study we explored whether the PGD2/CRTH2 pathway could affect the phenotypes of chronic asthma. Either CRTH2-deficient (CRTH2–/–) or wild-type mice were sensitized and exposed to ovalbumin (OVA) for 3 days (acute model) or 6 weeks (chronic model). While the magnitude of the acute eosinophilic inflammation was equivalent between CRTH2–/– and wild-type mice, the number of inflammatory cells and eosinophils in bronchoalveolar lavage fluid after chronic OVA exposure was significantly reduced in CRTH2–/– mice (18.0 ± 2.6 × 104 cells and 2.0 ± 0.5 × 104 cells) compared to wild-type mice (27.9 ± 2.5 × 104 cells and 6.8 ± 1.1 × 104 cells, p < 0.001). On the contrary, no difference was observed between CRTH2–/– and wild-type mice in terms of airway hyperresponsiveness or remodeling (goblet cell hyperplasia) in the chronic model of asthma. In conclusion, CRTH2 that mediates PGD2 activity is essential for sustained eosinophilic inflammation in the airways, and its antagonists could exert an anti-inflammatory effect in chronic asthma.
Expression and Effects of IL-33 and ST2 in Allergic Bronchial Asthma: IL-33 Induces Eotaxin Production in Lung Fibroblasts
Authors: Kurokawa Masatsugu , Matsukura Satoshi , Kawaguchi Mio , Ieki Koushi , Suzuki Shintaro , Odaka Miho , Watanabe Shin , Homma Tetsuya , Sato Masayuki , Yamaguchi Munehiro , Takeuchi Hiroko , Adachi Mitsuru
Published: June 2011

Background: Interleukin (IL)-33, a new member of the IL-1 cytokine family, has been recognized as a key cytokine that enhances T helper 2-balanced immune regulation through its receptor ST2; however, the function and relationship of the IL-33 and ST2 pathways in bronchial asthma are still unclear. We investigated the cellular origin and regulation of IL-33 and ST2 in allergic bronchial asthma in vivo and in vitro. Methods: BALB/c mice were sensitized by intraperitoneal injections of ovalbumin (OVA) with alum. Mice were exposed to aerosolized 1% OVA for 30 min a day for 7 days. These mice were then challenged with aerosolized 1% OVA 2 days after the last day of exposure. After the OVA challenge, the mice were sacrificed and their lung tissues were obtained. Mouse lung fibroblasts were cultured and treated with IL-33 or IL-13. Results: The levels of IL-33 mRNA and IL-33 protein in lung tissue increased after the OVA challenge. Most IL-33-expressing cells were CD11c+ cells and epithelial cells, and many ST2-expressing cells were stained lung fibroblasts and inflammatory cells. IL-33 induced eotaxin/CCL11 production in lung fibroblasts. IL-33 and IL-13 synergistically induced eotaxin expression. Conclusions: IL-33 may contribute to the induction and maintenance of eosinophilic inflammation in the airways by acting on lung fibroblasts. IL-33 and ST2 may play important roles in allergic bronchial asthma.
Differential Effects of Corticosteroids on Serum Eosinophil Cationic Protein and Cytokine Production in Rhinovirus- and Respiratory Syncytial Virus-Induced Acute Exacerbation of Childhood Asthma
Authors: Kato Masahiko , Yamada Yoshiyuki , Maruyama Kenichi , Hayashi Yasuhide
Published: June 2011

Background: Little information is available on eosinophil activation and the cytokine profile in virus-induced acute exacerbation of bronchial asthma; therefore, we examined the effects of treatments that included systemic corticosteroids on serum eosinophil cationic protein (ECP) and 17 cytokines/chemokines in rhinovirus- and respiratory syncytial (RS) virus-induced acute exacerbation of childhood asthma. Methods: We measured the peripheral eosinophil count, as well as the serum levels of ECP and 17 types of cytokines/chemokines (IL-1β, 2, 4, 5, 6, 7, 8, 10, 12, 13, and 17 and IFN-γ, TNF-α, GM-CSF, G-CSF, MCP-1, and MIP-1β), using a multiplex bead-based assay in 21 cases of rhinovirus- and 12 cases of RS virus-induced acute exacerbation of childhood asthma and 13 controls. We also compared the clinical data and the effects of systemic corticosteroids on these responses between rhinovirus and RS virus groups. Results: The serum levels of ECP, IL-5, and IL-6 were significantly elevated in patients with rhinovirus-induced acute exacerbation of asthma compared with controls, while serum IL-1β and IFN-γ were significantly lower in patients with rhinovirus-induced acute exacerbation of asthma than in controls. On the other hand, in RS virus-induced acute exacerbation of asthma, only the peripheral eosinophil count was significantly decreased compared with that in rhinovirus-induced acute exacerbation of asthma and controls. Furthermore, the serum levels of ECP, IL-5, and IL-6 in rhinovirus-induced acute exacerbation of asthma and levels of G-CSF in RS virus-induced acute exacerbation of asthma were significantly reduced after treatments that included systemic corticosteroids, respectively. Conclusion: These results suggest that the effects of systemic corticosteroids on serum ECP and the cytokine profile are different between rhinovirus- and RS virus-induced acute exacerbation of childhood asthma.
Role of the Arylhydrocarbon Receptor in Lung Disease
Authors: Chiba Takahito , Uchi Hiroshi , Yasukawa Fumiko , Furue Masutaka
Published: June 2011

Ubiquitous environmental contaminants such as dioxins have long been implicated in cellular toxicity, but only recently have various biological effects been linked to immune regulation. These plentiful noxious agents exert their effects through the arylhydrocarbon receptor (AhR) recognized as a ligand-activated transcription factor. AhR activation mediates gene alteration, cell-cell adhesion interaction, cytokine expression, and mucin production, which are involved in the induction of cancer or inflammation. We have reported that human bronchial epithelial cells express AhR, and AhR activation induces mucin production through reactive oxygen species. This review discusses the role of AhR in lung disease, focusing in particular on airway epithelial cells. In addition, although it is not yet clear how the activation of AhR modifies carcinogenesis or airway inflammation, we mention a potent therapeutic target for AhR activation in the prevention/treatment of lung cancer, allergic asthma, and chronic obstructive pulmonary disease.
Decreased Expression of Liver X Receptor-α in Macrophages Infected with Chlamydia pneumoniae in Human Atherosclerotic Arteries in situ
Authors: Bobryshev Yuri V. , Orekhov Alexander N. , Killingsworth Murray C. , Lu Jinhua
Published: June 2011

In in vitro experiments, Chlamydia pneumoniae has been shown to infect macrophages and to accelerate foam cell formation. It has been hypothesized that the C. pneumoniae infection affects foam cell formation by suppressing the expression of liver X receptors (LXR), but whether such an event occurs in human atherosclerosis is not known. In this study we examined carotid artery segments, obtained by endarterectomy, in which the presence of C. pneumoniae was confirmed by both polymerase chain reaction and immunohistochemistry. The expression of LXR-α in macrophages infected with C. pneumoniae and macrophages that were not infected was compared using a quantitative immunohistochemical analysis. The analysis revealed a 2.2-fold reduction in the expression of LXR-α in C. pneumoniae-infected cells around the lipid cores in atherosclerotic plaques. In the cytoplasm of laser-capture microdissected cells that were immunopositive for C. pneumoniae, electron microscopy demonstrated the presence of structures with the appearance of elementary, reticulate and aberrant bodies of C. pneumoniae. We conclude that LXR-α expression is reduced in C. pneumoniae-infected macrophages in human atherosclerotic lesions which supports the hypothesis that C. pneumoniae infection might suppress LXR expression in macrophages transforming into foam cells.
Lung Cancer in Chronic Hypersensitivity Pneumonitis
Authors: Kuramochi J. , Inase N. , Miyazaki Y. , Kawachi H. , Takemura T. , Yoshizawa Y.
Published: June 2011

Background: So far, the association of lung cancer with chronic hypersensitivity pneumonitis (CHP) has not been studied. Objective: We examined the prevalence and revealed clinical features of lung cancer in CHP. Methods: We retrospectively reviewed the medical records from 1994 through 2005 and identified 11 patients (15 lesions) with lung cancer among 104 patients with CHP. Their clinical features and histopathological findings were analyzed. Results: Ten men and 1 woman with a median age of 68.9 years were included. All patients had a smoking history. The most prevalent histopathological type of lung cancer was squamous cell carcinoma (53%), and all tumors were located in the peripheral region of the lung. Four patients suffered from lung cancer after the diagnosis of CHP and 1 patient had lung cancer before the diagnosis of CHP. The histological pattern of CHP showed a predominantly usual interstitial pneumonia-like lesion. Tumors were located adjacent to honeycombing in 7 (47%) of 15 lesions, bullae in 4 (27%) lesions, and relatively normal lung in 4 lesions. Conclusions: Since the prevalence of lung cancer in CHP seems to be high (10.6%) as seen in idiopathic pulmonary fibrosis, physicians should be aware of the possible complication of lung cancer in CHP.
A Phase I Study of the Safety and Pharmacokinetics of the Hypoxia-Activated Prodrug TH-302 in Combination with Doxorubicin in Patients with Advanced Soft Tissue Sarcoma
Authors: Ganjoo Kristen N. , Cranmer Lee D. , Butrynski James E. , Rushing Daniel , Adkins Douglas , Okuno Scott H. , Lorente Gustavo , Kroll Stew , Langmuir Virginia K. , Chawla Sant P.
Published: June 2011

Purpose: The purpose of this study was to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), safety, pharmacokinetics and preliminary activity of TH-302, a hypoxia-activated prodrug, in combination with doxorubicin in patients with advanced soft tissue sarcoma. Patients and Methods: TH-302 was administered intravenously on days 1 and 8 and doxorubicin 75 mg/m2 on day 1 (2 h after TH-302) of every 3-week cycle. TH-302 starting dose was 240 mg/m2 with a classic 3 + 3 dose escalation. Pharmacokinetics were assessed on days 1 and 8 of cycle 1. Tumor assessments were performed after every second cycle. Results: Sixteen patients enrolled. Prophylactic growth factor support was added due to grade 4 neutropenia. The MTD was 300 mg/m2. DLTs at 340 mg/m2 were neutropenia-associated infection and grade 4 thrombocytopenia. Common adverse events included fatigue, nausea and skin rash. There was no evidence of pharmacokinetic interaction between TH-302 and doxorubicin. Five of 15 (33%) evaluable patients had a partial response by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Conclusions: The hematologic toxicity of doxorubicin is increased when combined with TH-302. This can be mitigated by prophylactic growth factor support. Toxicities were manageable and there was evidence of antitumor activity.
Nutrigenetics and Prostate Cancer: 2011 and Beyond
Authors: Yuan Yinan , Ferguson Lynnette R.
Published: June 2011

Background/Aims: Prostate cancer runs in families and shows a clear dietary involvement. Until recently, the key risk gene(s) have proved elusive. We summarise current understandings of nutrient-gene interactions in prostate cancer risk and progression. Methods: A MEDLINE-based literature search was conducted. Results: Hypothesis-directed candidate gene approaches provide plausible, albeit statistically weak, nutrient-gene interactions. These are based on early understandings of factors likely to impact on carcinogenesis, including both nutrient and genetic effects on androgen biosynthesis and action, xenobiotic metabolism, DNA damage and DNA repair. Non-hypothesis-directed genome-wide association studies provide much stronger evidence for other genes, not hitherto suspected for involvement. Although only a few of these have been formally tested for dietary associations in well-designed epidemiologic studies, the nature of many of the genes suggests that their activity may be regulated by nutrients. These effects may not only be relevant to prostate cancer susceptibility, but also to disease progression. Conclusions: It will be important to move beyond studying single nucleotide polymorphisms, into more complex chromosomal rearrangements and to epigenetic changes. For future progress, large international cohorts will not only need to provide proof of individual nutrient-gene interactions, but also to relate these to more complex nutrient-gene-gene interactions, as parts of pathways. Bioinformatics and biostatistics will be increasingly important tools in nutrigenetic studies beyond 2011.
Elevated Levels of Triglyceride and Triglyceride-Rich Lipoprotein Triglyceride Induced by a High-Carbohydrate Diet Is Associated with Polymorphisms of APOA5-1131T>C and APOC3-482C>T in Chinese Healthy Young Adults
Authors: Lin Jia , Fang Ding Zhi , Du Juan , Shigdar Sarah , Xiao Li Ying , Zhou Xue Dong , Duan Wei
Published: June 2011

Background/Aims: Changes in lipid profiles have been shown to be associated with diet and apolipoprotein (APO) polymorphisms. Therefore, 2 polymorphisms, i.e. APOA5-1131T>C and APOC3-482C>T, and serum lipids were examined in a Chinese healthy young population with high-carbohydrate/low-fat (HC/LF) diet intervention. Methods: After a wash-out diet for 7 days, 56 young adults (22.89 ± 1.80 years) received the HC/LF diet for 6 days. Body mass index (BMI) and fasting serum lipid profiles at baseline, after the wash-out diet, and after the HC/LF diet were measured. Results: APOA5-1131C carriers had higher triglyceride (TG) and TG-rich lipoprotein TG (TRL-TG) levels at baseline and after the HC/LF diet, though this mainly corresponded to the female cohort. APOC3-482T carriers had higher TRL-TG levels following the wash-out and HC/LF diets, but these were not directly attributable to a single gender. Conclusions: Both polymorphisms may play an important role in the elevated TG and TRL-TG levels induced by the HC/LF diet, especially in females, thus indicating a potential dietary prevention of coronary heart disease in this Chinese cohort.
Electrophysiological Assessment of the Autonomic Nervous System in Male Patients with Acromegaly
Authors: Öz Oğuzhan , Taşlıpınar Abdullah , Yücel Mehmet , Akgün Hakan , Ulaş Ümit Hıdır , Bolu Erol , Kütükçü Yaşar , Odabaşı Zeki
Published: June 2011

Background/Aims: We aimed to electrophysiologically evaluate the autonomic function in acromegalic patients using sympathetic skin response (SSR) as a reflection of the sympathetic sudomotor activity and RR interval variation (RRIV) as an indicator of the cardiovagal autonomic function. Methods: The study group consisted of 18 male acromegalics, and the control group was composed of 18 age- and sex-matched healthy subjects. Participants underwent SSR and RRIV tests. Beginning latencies and amplitudes of the median and tibial SSRs were compared among the groups. The RRIV values recorded at rest and during hyperventilation were compared among the patients and controls. Results: Latencies of SSRs recorded from the palms (median) and soles (tibial) of acromegalics were significantly longer than in healthy subjects (p = 0.004, p < 0.001). The amplitude of SSR recorded from the sole (tibial) was significantly decreased (p = 0.028). The RRIVs obtained from acromegalics at rest and during hyperventilation were significantly decreased compared with those of controls (p < 0.001). The RRIVs obtained from controls prolonged significantly during hyperventilation (p < 0.001); however, in the acromegaly group, hyperventilation did not cause a significant change in RRIV (p = 0.983). Conclusions: The present study suggests that an autonomic dysfunction exists in patients with acromegaly. Dysautonomia in acromegalics may be documented by means of SSR and RRIV.
A Rapid Quantitative Real-Time PCR-Based DNA Quantification Assay Coupled with Species – Assignment Capabilities for Two Hybridizing Macaca Species
Authors: Barr A. , Premasuthan A. , Satkoski J. , Smith D.G. , George D. , Kanthaswamy S.
Published: June 2011

Regional populations of rhesus and long-tailed macaques exhibit fundamental differences in mitochondrial DNA, short tandem repeat and single nucleotide polymorphism variation between mainland and insular Southeast Asian populations. Some studies have revealed genetic admixture between these species due to natural hybridization and human-assisted intercrosses. A quantitative real-time PCR (qPCR) assay was developed to efficiently determine the species of origin of a macaque biological sample, and to quantify the species-specific template DNA. Prior knowledge of species identity and DNA concentrations are crucial for maintaining cost-effective methods and accurate DNA analysis. DNA from 109 regionally representative rhesus and long-tailed macaques was qPCR amplified to determine the species and template quantities. Of the 19 Vietnamese long-tailed macaques, 3 samples were discovered to be hybrids.
Orangutans (Pongo pygmaeus) Do Not Form Expectations Based on Their Partner’s Outcomes
Authors: Brosnan Sarah F. , Flemming Timothy , Talbot Catherine F. , Mayo Laura , Stoinski Tara
Published: June 2011

Several primate species form expectations based on others’ outcomes, responding negatively when their outcomes differ from their partners’. The function and evolutionary pathway of this behavior are unknown, in part because all of the species which have been tested thus far share traits related to a gregarious lifestyle, intelligence, and cooperativeness. Our goal was to test whether inequity is a homology among primates or a convergence by comparing one species known to show social comparisons, the chimpanzee, to another great ape which differs on several of these life history characteristics. Using a protocol identical to one used previously with chimpanzees, we tested whether orangutans, an intelligent but predominantly solitary species with few opportunities to cooperate, responded similarly. To allow for a strong comparison with chimpanzees (and other species), we used socially housed adults of both sexes, tested with members of their social group. Orangutans did not respond negatively to inequity, supporting previous findings and indicating that inequity responses in apes are likely a convergence based on either sociality or cooperative tendency. These results in such closely related species highlight the need for additional comparative studies to understand better the function and evolution of social behaviors.
Uptake of Antioxidants by Natural Nutrition and Supplementation: Pros and Cons from the Dermatological Point of View
Authors: Lademann J. , Patzelt A. , Schanzer S. , Richter H. , Meinke M.C. , Sterry W. , Zastrow L. , Doucet O. , Vergou T. , Darvin M.E.
Published: June 2011

The pros and cons of the systemic and topical application of antioxidant substances are a subject of intense discussion among experts, with resulting confusion for consumers and producers. The objective of the present article is to clarify the various uncertainties relating to the use of antioxidant substances in dermatology. Whereas inappropriate application of antioxidant substances (concerning their concentration and composition) might induce harmful effects, the consumer will definitively benefit from physiological concentrations and compositions of antioxidants. The most suitable method is the consumption of natural antioxidants in the form of fruit and vegetables, for example. In addition, the skin, which also accumulates antioxidant substances, may profit from a sufficient antioxidative level, as damage induced by sun radiation in addition to skin aging is reduced.
Sensitive Cardiac Troponin T Assay and the Risk of Incident Cardiovascular Disease in Women With and Without Diabetes Mellitus
Authors: Everett Brendan M. , Cook Nancy R. , Magnone Maria C. , Bobadilla Maria , Kim Eunjung , Rifai Nader , Ridker Paul M , Pradhan Aruna D.
Published: June 2011

Background—

Very low levels of cardiac troponin T are associated with an increased risk of cardiovascular death in patients with stable chronic coronary disease. Whether high-sensitivity cardiac troponin T levels are associated with adverse cardiovascular outcomes in individuals without cardiovascular disease (CVD) has not been well studied.

Methods and Results—

Using 2 complementary study designs, we evaluated the relationship between baseline cardiac troponin and incident CVD events among diabetic and nondiabetic participants in the Women's Health Study (median follow-up, 12.3 years). All diabetic women with blood specimens were included in a cohort study (n=512 diabetic women, n=65 events), and nondiabetic women were sampled for inclusion in a case-cohort analysis (n=564 comprising the subcohort, n=479 events). High-sensitivity cardiac troponin T was detectable (≥0.003 μg/L) in 45.5% of diabetic women and 30.3% of nondiabetic women (
P
<0.0001). In models adjusted for traditional risk factors and hemoglobin A
1c
, detectable high-sensitivity cardiac troponin T was associated with subsequent CVD (myocardial infarction, stroke, cardiovascular death) in diabetic women (adjusted hazard ratio, 1.79; 95% confidence interval, 1.04 to 3.07,
P
=0.036) but not nondiabetic women (adjusted hazard ratio, 1.13; 95% confidence interval, 0.82 to 1.55;
P
=0.46). Further adjustment for amino-terminal pro-B-type natriuretic peptide and estimated renal function did not substantially alter this relationship among diabetic women (hazard ratio, 1.76; 95% confidence interval, 1.00 to 3.08;
P
=0.0499), which appeared to be driven by a 3-fold increase in CVD death that was not observed in nondiabetic women.

Conclusions—

Very low but detectable levels of cardiac troponin T are associated with total CVD and CVD death in women with diabetes mellitus. Among healthy nondiabetic women, detectable compared with undetectable troponin was not associated with CVD events.
Calcineurin Splicing Variant Calcineurin Aβ1 Improves Cardiac Function After Myocardial Infarction Without Inducing Hypertrophy
Authors: Felkin Leanne E. , Narita Takuya , Germack Renée , Shintani Yasunori , Takahashi Kunihiko , Sarathchandra Padmini , López-Olañeta Marina M. , Gómez-Salinero Jesús M. , Suzuki Ken , Barton Paul J.R. , Rosenthal Nadia , Lara-Pezzi Enrique
Published: June 2011

Background—

Calcineurin is a calcium-regulated phosphatase that plays a major role in cardiac hypertrophy. We previously described that alternative splicing of the calcineurin Aβ (CnAβ) gene generates the CnAβ1 isoform, with a unique C-terminal region that is different from the autoinhibitory domain present in all other CnA isoforms. In skeletal muscle, CnAβ1 is necessary for myoblast proliferation and stimulates regeneration, reducing fibrosis and accelerating the resolution of inflammation. Its role in the heart is currently unknown.

Methods and Results—

We generated transgenic mice overexpressing CnAβ1 in postnatal cardiomyocytes under the control of the α-myosin heavy chain promoter. In contrast to previous studies using an artificially truncated calcineurin, CnAβ1 overexpression did not induce cardiac hypertrophy. Moreover, transgenic mice showed improved cardiac function and reduced scar formation after myocardial infarction, with reduced neutrophil and macrophage infiltration and decreased expression of proinflammatory cytokines. Immunoprecipitation and Western blot analysis showed interaction of CnAβ1 with the mTOR complex 2 and activation of the Akt/SGK cardioprotective pathway in a PI3K-independent manner. In addition, gene expression profiling revealed that CnAβ1 activated the transcription factor ATF4 downstream of the Akt/mTOR pathway to promote the amino acid biosynthesis program, to reduce protein catabolism, and to induce the antifibrotic and antiinflammatory factor growth differentiation factor 15, which protects the heart through Akt activation.

Conclusions—

Calcineurin Aβ1 shows a unique mode of action that improves cardiac function after myocardial infarction, activating different cardioprotective pathways without inducing maladaptive hypertrophy. These features make CnAβ1 an attractive candidate for the development of future therapeutic approaches.
Early Repolarization
Authors: Tikkanen Jani T. , Junttila M. Juhani , Anttonen Olli , Aro Aapo L. , Luttinen Samuli , Kerola Tuomas , Sager Solomon J. , Rissanen Harri A. , Myerburg Robert J. , Reunanen Antti , Huikuri Heikki V.
Published: June 2011

Background—

Early repolarization (ER) in inferior/lateral leads of standard ECGs increases the risk of arrhythmic death. We tested the hypothesis that variations in the ST-segment characteristics after the ER waveforms may have prognostic importance.

Methods and Results—

ST segments after ER were classified as horizontal/descending or rapidly ascending/upsloping on the basis of observations from 2 independent samples of young healthy athletes from Finland (n=62) and the United States (n=503), where ascending type was the dominant and common form of ER. Early repolarization was present in 27/62 (44%) of the Finnish athletes and 151/503 (30%) of the US athletes, and all but 1 of the Finnish (96%) and 91/107 (85%) of US athletes had an ascending/upsloping ST variant after ER. Subsequently, ECGs from a general population of 10 864 middle-aged subjects were analyzed to assess the prognostic modulation of ER-associated risk by ST-segment variations. Subjects with ER ≥0.1 mV and horizontal/descending ST variant (n=412) had an increased hazard ratio of arrhythmic death (relative risk 1.43; 95% confidence interval 1.05 to 1.94). When modeled for higher amplitude ER (>0.2 mV) in inferior leads and horizontal/descending ST-segment variant, the hazard ratio of arrhythmic death increased to 3.14 (95% confidence interval 1.56 to 6.30). However, in subjects with ascending ST variant, the relative risk for arrhythmic death was not increased (0.89; 95% confidence interval 0.52 to 1.55).

Conclusions—

ST-segment morphology variants associated with ER separates subjects with and without an increased risk of arrhythmic death in middle-aged subjects. Rapidly ascending ST segments after the J-point, the dominant ST pattern in healthy athletes, seems to be a benign variant of ER.
Birth Weight Predicts Risk of Cardiovascular Disease Within Dizygotic but Not Monozygotic Twin Pairs
Authors: Öberg Sara , Cnattingius Sven , Sandin Sven , Lichtenstein Paul , Iliadou Anastasia N.
Published: June 2011

Background—

The widely reported inverse association between birth weight and risk of cardiovascular disease (CVD) has sparked theories about early life determinants of adult disease. Within-twin-pair analysis provides a unique opportunity to investigate whether factors shared within twin pairs influence the association.

Methods and Results—

In a population-based cohort of like-sexed twins with known zygosity born in Sweden from 1926 to 1958, disease-discordant twin pairs were identified through linkage to the National Inpatient and Cause of Death registers between 1973 and 2006. Co-twin–control analyses were performed on twins discordant for cardiovascular disease (n=3884), coronary heart disease (n=2668), and stroke (n=1372). Overall, inverse associations between birth weight and risk of cardiovascular diseases were seen within dizygotic but not monozygotic twin pairs. In dizygotic twins, the odds ratios for a 1-kg within-pair increase in birth weight were 0.74 (95% confidence interval, 0.56 to 0.98) for coronary heart disease and 0.57 (95% confidence interval, 0.37 to 0.88) for stroke. Conversely, no statistically significant associations were found within monozygotic twins (for coronary heart disease: odds ratio, 1.10; 95% confidence interval, 0.73 to 1.68; for stroke: odds ratio, 0.92; 95% confidence interval, 0.48 to 1.80).

Conclusions—

We found an association between birth weight and risk of cardiovascular disease within disease-discordant dizygotic but not monozygotic twin pairs. This indicates that the association between birth weight and cardiovascular disease could be a result of common causes, and that factors that vary within dizygotic but not monozygotic twin pairs may help identify them.
Effect of a Reduction in Uric Acid on Renal Outcomes During Losartan Treatment
Authors: Miao Yan , Ottenbros Stefan A. , Laverman Goos D. , Brenner Barry M. , Cooper Mark E. , Parving Hans-Henrik , Grobbee Diederick E. , Shahinfar Shahnaz , de Zeeuw Dick , Lambers Heerspink Hiddo J.
Published: June 2011

Emerging data show that increased serum uric acid (SUA) concentration is an independent risk factor for end-stage renal disease. Treatment with the antihypertensive drug losartan lowers SUA. Whether reductions in SUA during losartan therapy are associated with renoprotection is unclear. We therefore tested this hypothesis. In a post hoc analysis of 1342 patients with type 2 diabetes mellitus and nephropathy participating in the Reduction of Endpoints in Non-Insulin-Dependent Diabetes Mellitus With the Angiotensin II Antagonist Losartan Trial, we determined the relationship between month 6 change in SUA and renal endpoints, defined as a doubling of serum creatinine or end-stage renal disease. Baseline SUA was 6.7 mg/dL in placebo and losartan-treated subjects. During the first 6 months, losartan lowered SUA by −0.16 mg/dL (95% CI: −0.30 to −0.01;
P
=0.031) as compared with placebo. The risk of renal events was decreased by 6% (95% CI: 10% to 3%) per 0.5-mg/dL decrement in SUA during the first 6 months. This effect was independent of other risk markers, including estimate glomerular filtration rate and albuminuria. Adjustment of the overall treatment effects for SUA attenuated losartan's renoprotective effect from 22% (95% CI: 6% to 35%) to 17% (95% CI: 1% to 31%), suggesting that approximately one fifth of losartan's renoprotective effect could be attributed to its effect on SUA. Losartan lowers SUA levels compared with placebo treatment in patients with type 2 diabetes mellitus and nephropathy. The degree of reduction in SUA is subsequently associated with the degree in long-term renal risk reduction and explains part of losartan's renoprotective effect. These findings support the view that SUA may be a modifiable risk factor for renal disease.
Singular Vectors for Tropical Cyclone–Like Vortices in a Nondivergent Barotropic Framework
Authors: Yamaguchi Munehiko , Nolan David S. , Iskandarani Mohamed , Majumdar Sharanya J. , Peng Melinda S. , Reynolds Carolyn A.
Published: June 2011

In this study, singular vectors (SVs) are calculated for tropical cyclone (TC)–like vortices on an f plane and β plane using a barotropic model, and the structure and time evolution of the SVs are investigated. In the f-plane study, SVs are calculated for TC-like vortices that do and do not satisfy a necessary condition of barotropic instability of normal modes, in which the vorticity gradient changes sign. It is found that, in the case where the initial vortices do not meet the condition, 1) the SVs are tilted against the shear of the background angular velocity as found earlier by Nolan and Farrell, indicating the growth of SVs through the Orr mechanism; 2) the leading singular value increases with the maximum tangential wind speed Vmax and decreases with the radius of the maximum wind (RMW); and 3) the locations of SVs move outward with increasing RMW, Vmax, and the optimization time. In the case where the initial vortex allows for barotropic instability, the SV is initially tilted against the background shear and exhibits transient growth for a limited period. At a certain time during the initial growth, the SV “locks in” to a normal mode structure and remains in that structure so that it may grow exponentially with time.

In contrast to the SVs on an f plane, the azimuthal distribution of the SVs on a β plane becomes more asymmetric, and the extent of the asymmetry increases as the strength of the beta gyres increases. On the β plane, all first and second SVs calculated in this study have an azimuthal wavenumber-1 structure at the optimization time, regardless of whether the vorticity gradient of initial TC-like vortices changes sign and the TC-like vortices include the beta gyres at initial time. It is found that when the first and second SVs are used as ensemble initial perturbations, the linear combination of the initial first and second SVs can shift the vortex toward any direction at the optimization time. This is true even when SVs with a low horizontal resolution are used as initial perturbations, as in the European Centre for Medium-Range Weather Forecasts (ECMWF) and Japan Meteorological Agency (JMA) ensemble prediction system. Such wavenumber-1 perturbations could be useful for generating sufficient spread among the tropical cyclone tracks in ensemble forecasts.
Extreme Cold Winter Temperatures in Europe under the Influence of North Atlantic Atmospheric Blocking
Authors: Sillmann Jana , Croci-Maspoli Mischa , Kallache Malaak , Katz Richard W.
Published: June 2011

North Atlantic atmospheric blocking conditions explain part of the winter climate variability in Europe, being associated with anomalous cold winter temperatures. In this study, the generalized extreme value (GEV) distribution is fitted to monthly minima of European winter 6-hourly minimum temperatures from the ECHAM5/MPI-OM global climate model simulations and the ECMWF reanalysis product known as ERA-40, with an indicator for atmospheric blocking conditions being used as covariate. It is demonstrated that relating the location and scale parameter of the GEV distribution to atmospheric blocking improves the fit to extreme minimum temperatures in large areas of Europe. The climate model simulations agree reasonably with ERA-40 in the present climate (1961–2000). Under the influence of atmospheric blocking, a decrease in the 0.95th quantiles of extreme minimum temperatures can be distinguished. This cooling effect of atmospheric blocking is, however, diminished in future climate simulations because of a shift in blocking location, and thus reduces the chances of very cold winters in northeastern parts of Europe.
Response of the Indian Ocean Basin Mode and Its Capacitor Effect to Global Warming*
Authors: Zheng Xiao-Tong , Xie Shang-Ping , Liu Qinyu
Published: June 2011

The development of the Indian Ocean basin (IOB) mode and its change under global warming are investigated using a pair of integrations with the Geophysical Fluid Dynamics Laboratory Climate Model version 2.1 (CM2.1). In the simulation under constant climate forcing, the El Niño–induced warming over the tropical Indian Ocean (TIO) and its capacitor effect on summer northwest Pacific climate are reproduced realistically. In the simulation forced by increased greenhouse gas concentrations, the IOB mode and its summer capacitor effect are enhanced in persistence following El Niño, even though the ENSO itself weakens in response to global warming. In the prior spring, an antisymmetric pattern of rainfall–wind anomalies and the meridional SST gradient across the equator strengthen via increased wind–evaporation–sea surface temperature (WES) feedback. ENSO decays slightly faster in global warming. During the summer following El Niño decay, the resultant decrease in equatorial Pacific SST strengthens the SST contrast with the enhanced TIO warming, increasing the sea level pressure gradient and intensifying the anomalous anticyclone over the northwest Pacific. The easterly wind anomalies associated with the northwest Pacific anticyclone in turn sustain the SST warming over the north Indian Ocean and South China Sea. Thus, the increased TIO capacitor effect is due to enhanced air–sea interaction over the TIO and with the western Pacific. The implications for the observed intensification of the IOB mode and its capacitor effect after the 1970s are discussed.
A Bayesian Forecast Model of Australian Region Tropical Cyclone Formation
Authors: Werner Angelika , Holbrook Neil J.
Published: June 2011

A new and potentially skillful seasonal forecast model of tropical cyclone formation [tropical cyclogenesis (TCG)] is developed for the Australian region. The model is based on Poisson regression using the Bayesian approach. Predictor combinations are chosen using a step-by-step predictor selection. The three-predictor model based on derived indices of June–August average convective available potential energy, May–July average meridional winds at 850 hPa (V850), and July–September geopotential height at 500 hPa produces the smallest standard error (se = 0.36) and root-mean-squared error (RMSE = 5.20) for the leave-one-out cross-validated TCG hindcasts over the 40-yr record between 1968/69–2007/08. The corresponding correlation coefficient between observed annual TCG totals and cross-validated model hindcasts is r = 0.73. Using fourfold cross validation, model hindcast skill is robust, with 85% of the observed seasonal TCG totals hindcast within the model standard deviations. Seasonal TCG totals during ENSO events are typically well captured with RMSE = 5.14 during El Niño, and RMSE = 6.04 during La Niña years. The model is shown to be valuable in hindcasting seasonal TCG totals in the eastern Australian subregion (r = 0.73) and also provides some skill for the western Australian region (r = 0.42), while it not useful for the northern region. In summary, the authors find that the three-predictor Bayesian model provides substantial improvement over existing statistical TCG forecast models, with remarkably skillful hindcasts (forecasts) of Australian region and subregional seasonal TCG totals provided one month ahead of the TC season.