bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B72: Resolvin D1, derived from n-3 polyunsaturated fatty acid, stimulates efferocytosis and protects macrophages from oxidative stress-induced apoptosis
Authors: Lee Ha-Na , Kundu Joydeb Kumar , Shin Jun-Wan , Cha Young-Nam , Surh Young-Joon
Published: June 2012

Phagocytosis of apoptotic neutrophils by macrophages, called efferocytosis, is critical to resolution of inflammation as this process prevents the exposure of surrounding tissues at the inflammatory site to the toxic contents of lytic cells. Docosahexaenoic acid (DHA)-derived resolvin D1 (RvD1), endogenously generated during resolution of inflammation, is known to stimulate efferocytosis, but little is known about the mechanism of its action. In the present study, we found that lipopolysaccharide (LPS; 200 g/ml) suppressed efferocytosis by murine macrophage-like RAW264.7 cells, and RvD1 (50 nM) restored the phagocytic ability of these cells by down-regulating TNF-α expression. The inhibitory effect of RvD1 on LPS-induced TNF-α expression was associated with enhanced nuclear localization of p50/p50 homodimer and concomitant reduction in the nuclear levels of p65/p50 heterodimer. siRNA knockdown of NF-κB p50 abolished RvD1-mediated suppression of TNF-α expression and resulted in impaired efferocytosis, suggesting that the replacement of p65/p50 with p50/p50 homodimer is an essential event for RvD1-mediated stimulation of efferocytosis. In a murine peritonitis model, intraperitoneal administration of RvD1 (300 ng) abrogated zymosan A (30 mg/kg)-induced TNF-α production, thereby reactivating efferocytosis. In addition, RvD1 protected RAW264.7 cells from oxidative stress-induced apoptosis during efferocytosis. The generation of reactive oxygen species after efferocytosis was markedly blocked in RvD1-exposed macrophages. Moreover, RvD1 upregulated the anti-apoptotic Bcl-2 and Bcl-xL expression and downregulated the proapoptotic Bax and Bad expression. In conclusion, RvD1 expedites resolution of inflammation through stimulating efferocytosis while preserving viability of macrophage during efferocytosis. These findings account, at least in part, for the chemopreventive effects of DHA on inflammation-associated carcinogenesis.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B72.
Abstract B73: A novel chemopreventive molecular mechanism of selenium: p53-mediated DNA repair
Authors: Seo Young Rok
Published: June 2012

Selenium is an essential trace element which has been considered as chemopreventive agent against cancer, due to its antioxidant activity. Among several selenium compounds, selenomethionine (SeMet) has significant protective effect toward various genotoxic stresses via stimulating DNA repair process. However, its mechanism is still not well elucidated. In this study, we examined the mechanism of SeMet in terms of p53-mediated base excision repair (BER). Our data showed that the amount of DNA damage was rapidly decreased in the presence of SeMet when methyl methanesulfonate (MMS), a BER-inducing agent, was treated in the cells. In addition, the removal of apurinic/apyrimidinic sites was significantly enhanced in p53-wild type cells in response to SeMet. Furthermore, we observed the Gadd45a, known to involve BER as one of the p53 downstream genes, was accumulated by SeMet in p53-wild type RKO cells. Indeed the interaction of BER-mediated repair proteins including PCNA (proliferating cell nucleus antigen) and APE/Ref-1 with Gadd45a was notably decreased by SeMet in p53 siRNA-treated cells. In in vivo study, the frequency and size of polyp in AOM/DSS model as an animal model for colitis-related carcinogenesis was decreased in response to SeMet. Moreover, proteins related with DNA repair including Trx (thioredoxin), p53 and Gadd45a were increased in SeMet treated AOM/DSS model. Those results suggested that BER activity might be dependent on wild type p53 under the modulation of protein complexes with Gadd45a and repair protein including PCNA and APE/Ref-1 as a distinct chemopreventive mechanism of SeMet. Our study might provide an important evidence to develop the chemopreventive strategies against various oxidative stresses.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B73.
Abstract B74: EGCG inhibits cancer invasion by regulating tumor-stromal crosstalk in oral squamous cell carcinoma
Authors: Bae Jung Yoon , Moon Sook , Kim Eun Kyoung , Kim Jin
Published: June 2012

Introduction: Epigallocatechin-3-O-gallate (EGCG), a major constituent polyphenol of green tea, has been shown to have suppressive effects on the invasion of various cancer cells, whereas the exact mechanisms have not yet been fully elucidated. In this study, the effects of EGCG on the invasion of oral squamous cell carcinoma (OSCC) were investigated where the new perspective focused on tumor-stromal crosstalk was emphasized, unlikely other previous studies focused on cancer cell mainly.

Materials and Methods: OSCC were cultured with or without carcinoma-associated fibroblasts (CAF) in the dose dependent treatment of EGCG. In order to investigate the invasiveness, invasion assay and zymography were examined. Based on our previous study found that several cytokines are concerned with tumor-stromal crosstalk in invasion of OSCC, RT-PCR and ELISA assay were employed to examine the influence of EGCG on the expression levels of cytokines.

Results: The invasiveness of OSCC was reduced by EGCG treatment, and the 50% reduction was demonstrated at the half concentration of EGCG (25 μM) in co-cultured group with CAF, compared to OSCC mono-cultured (50 μM). Zymography showed that EGCG treatment reduced MMP-9 expression in co-cultured condition. In addition, EGCG resulted in a noticeable decrease in the expression of cytokines, especially GRO-α/CXCL1, concerned with tumor-stromal crosstalk in invasion of OSCC.

Conclusions: In this study, inhibitory effect of EGCG on cancer invasion was found at which its concentration is lower than previously known. Taking these results into consideration, EGCG may play an effective role in preventing invasion of OSCC by regulating tumor-stromal crosstalk.

Acknowledgement: This work was supported by Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010–0029702).

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B74.
Abstract B75: Resveratrol and its analogues as chemopreventive and anticancer agents in prostate cancer: Epigenetic mechanisms of action
Authors: Dias Steven J. , Li Kun , Dhar Swati , Ivanovic Marina , Rimando Agnes M. , Levenson Anait S.
Published: June 2012

Nutritional chemoprevention is a promising approach for prostate cancer (PCa) management. Resveratrol (Res), found in plants, has antioxidant, cardioprotective, anti-inflammatory and anticancer properties. Res may be considered as both a chemopreventive and chemotherapeutic agent on the basis of molecular and preclinical studies. We propose to investigate novel epigenetic mechanisms of the chemopreventive and anticancer effects of Res. We discovered that Res down-regulates metastasis-associated protein 1 (MTA1) by causing its proteasomal degradation. MTA1 levels correlate with cancer aggressiveness and metastases and, as a part of the nucleosome remodeling deacetylation (NuRD) complex, MTA1 plays a role in chromatin remodeling and transcriptional repression.

We hypothesize that MTA1 nuclear overexpression promotes PCa progression and metastasis by enhancing MTA1/HDAC1/NuRD deacetylation activity. We further hypothesize that Res, as a potent inhibitor of MTA1, exerts its anticancer effects, at least in part, through blocking MTA1/HDAC1/NuRD-mediated deacetylation. We propose: (1) determine the effects of Res on MTA1-mediated epigenetic modifications of PTEN and HIF-1α. We will use PCa cells with silenced MTA1 (shRNA-mediated knockdown) to examine the acetylation state of PTEN and HIF-1α in the presence or absence of Res. Transcriptional activation/repression of downstream signaling (PI3K/Akt) or target genes (VEGF) will be used as readouts. (2) evaluate MTA1-associated epigenetic anticancer effects of Res analogues in PCa. We will compare biopotency of natural and synthetic Res analogues in inhibiting MTA1, cell proliferation, invasion and migration in vitro. (3) evaluate MTA1-mediated Res chemopreventive and therapeutic efficacy in PCa mouse models. a. we will use orthotopic PCa xenografts to evaluate MTA1-mediated effects of Res on PCa initiation, progression and metastasis; b. we will evaluate Res chemopreventive and therapeutic effects using autochthonous, prostate-specific Pten −/− mouse model.

Our study is the first to identify MTA1 as a specific molecular target of Res, further defining a novel epigenetic mechanism of Res anticancer activity as an HDAC inhibitor. The mechanism-based studies will significantly contribute to a better understanding of the role of MTA1 as an upstream epigenetic regulator of tumor suppressors and oncogenes. The results from this study will aid the development of preventive and curative strategies based on Res, its potent analogues, and synergy with other “epigenetic” agents. Our preclinical studies will provide a powerful base for initiating clinical trials in men.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B75.
Abstract CN03-03: Chemoprevention of lung cancer by metformin
Authors: Dennis Phillip A.
Published: June 2012

Metformin is the most widely prescribed drug for type II diabetes. Diabetics maintained on metformin have decreased incidence of several types of cancer, including lung cancer, compared to diabetics maintained on other anti-diabetic drugs. This retrospective analysis has raised the possibility that metformin might be an effective chemopreventive agent. In diabetics, metformin decreases hepatic gluconeogenesis and decreases circulating levels of IGF-I and insulin. In certain tissues such as liver, muscle, and fat, metformin activates AMP-activated kinase and inhibits mTOR, a kinase whose activity is required for lung tumorigenesis in several mouse models. We previously showed that metformin in the drinking water inhibits tobacco carcinogen-induced lung tumorigenesis in a mouse model of lung cancer. Inhibition of tumorigenesis occurred at steady state levels of metformin easily achieved in humans, and the mechanism of action in lung tissues appeared independent of AMPK but dependent upon inhibition of IGF-I receptor-mediated signaling. This presentation will describe the efficacy of metformin in other mouse models of lung cancer, identify additional tissue-specific biomarkers for metformin that might have predictive value, and discuss the design of clinical prevention trials with metformin.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN03-03.
Abstract CN07-03: IL6 and AKT as targets for chemoprevention
Authors: Ibarra-Drendall Catherine , Ford Anne , Tolbert Nora , Frye Endya , Lee Laurie , Broadwater Gloria , Barry William , Petricoin Emanuel , Liota Lance , Seewaldt Victoria
Published: June 2012

Background: Currently we lack adequate prevention strategies for triple-negative breast cancer; progress in designing targeted strategies is limited by a lack of knowledge of the biology of cancer initiation. The origins of triple-negative breast cancer in premenopausal women are poorly understood. Importantly, we do not understand whether the molecular pathways that underlie the aggressive behavior of triple-negative breast cancer can be detected in premalignant breast lesions. Growing evidence indicates that early mammary carcinogenesis is regulated by integrated signaling networks and not by isolated genes. Interleukin-6 (IL6) plays a role in stem cell regeneration, promotes epithelial to mesenchymal transition (EMT), and high IL6 serum levels predict a poor outcome in premenopausal women with triple-negative breast cancer.

Methods and Results: We used Reverse-Phase Protein Microarray (RPPM) profiling to test for activation of phosphoprotein signaling in premalignant Random Periareolar Fine Needle Aspiration (RPFNA) mammary epithelial cytology from 65 high-risk African American women. Unsupervised hierarchical clustering of RPPM proteomic analysis RPFNA aspirates identified three activated ER− signaling pathways including co-activation of Akt/mTOR/PI3K and IL6/pStat3/vimentin. Analysis of interstitial breast tissue demonstrated that high interstitial IL6/VEGF cytokine production predicted high epithelial expression of pStat3/vimentin. Based on these observations we are currently launching a prevention trial to target Akt/mTor using metformin 500 mg bid.

Conclusion: This is the first demonstration that Akt/mTor and IL6/Stat3/vimentin signaling is activated in pre-cancerous mammary epithelial cells from high-risk premenopausal women. Currently we are testing whether trials are on-going to test whether metformin can inhibit activation of mammary epithelial Akt/mTor and perhaps IL6/Stat3/vimentin signaling.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN07-03.
Abstract CN08-02: Psychological stress and disease progression
Authors: Andersen Barbara L.
Published: June 2012

A randomized clinical trial was designed to test the hypothesis that cancer patients coping with a cancer diagnosis but receiving a psychological intervention would have reduced risk for disease progression (1994). Patients (N=227) surgically treated for regional breast cancer participated. Before beginning adjuvant cancer therapies, patients were assessed with psychological and behavioral measures, had a health evaluation, and a 60 mL blood sample was drawn. Patients were randomized to Psychological Intervention or Assessment only arms. The intervention was psychologist led, conducted in small groups, and included strategies to reduce stress, improve mood, alter health behaviors, and maintain adherence to cancer treatment. Earlier papers (2004, 2007) showed that, compared to the Assessment arm, the Intervention arm improved across all of the latter secondary outcomes. T cell blastogenesis was also enhanced. An interim paper (2007) clarified treatment mechanisms in the Intervention arm. First, patients were satisfied with the intervention, but it was group cohesion that related to better outcomes. Second, offering patients a stress conceptualization (Selye) and teaching them multiple coping strategies related to better health. Third, three relationships between treatment utilization and outcomes are noted: 1) Relaxation training was associated with both distress reduction and symptom lowering. 2) Patients' use of assertive communication with health care providers was associated with better health outcomes. 3) Intervention strategy use was also associated with fewer signs/symptoms and cancer treatment toxicities. After a median of 11 years follow-up, recurrence occurred for 62 of 212 (29%) women and death for 54 of 227 (24%). Intent to treat hazard analyses showed, as predicted, Intervention arm patients had a reduced risk of recurrence [Hazard Ratio (HR)=0.55, P=.034] and breast cancer death (HR=0.44, P=.016). Follow up papers (2009) have examined the covariation of inflammation and distress during the period of intervention delivery (2009) and in the months prior to recurrence diagnosis (2008). Learning Objective 1: Show that a randomized clinical trial has produced evidence that a behavioral intervention can reduce fatal and nonfatal regional breast cancer recurrence. Learning Objective 2: Demonstrate that patients' use of assertive communication with health care providers was associated with better health outcomes.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN08-02.
Abstract ED05-02: Building a tobacco-free world: Engaging youth and young adults
Authors: Vallone Donna
Published: June 2012

A recent study by Christakis and Fowler (2008) found that when one or two people in a social network stop smoking, others in that network also tend to stop as well—highlighting both the importance of social networks and the potential to virally spread behavior change. Dr. Donna Vallone will discuss research related to prompting online social engagement and participation in the EX community, a component of the web-based smoking cessation program, www.becomeanex.org. Evidence suggests that these online social networks can provide social support to online smokers interested in quitting—a critical component of cessation treatment outlined in the US Clinical Guidelines for Smoking Cessation. Social media applications of EX on Facebook, Twitter and other channels will also be discussed.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):ED05-02.
Abstract ED06-02: Breast cancer screening in low- and middle-income countries
Authors: Yip Cheng-Har
Published: June 2012

Breast cancer is the commonest cancer in the majority of low and middle income countries (LMIC's). Survival from breast cancer depends on two main factors – early detection and treatment. In LMICs, delayed presentation of breast cancer is a common occurrence. Barriers to early presentation are lack of access to optimal treatment, lack of financial resources, ignorance and psychosocial issues which include fatalism, fear of death, fear of mastectomy, and lack of autonomy on the part of the woman. Downsizing symptomatic disease as well as screening for asymptomatic disease can reduce mortality from breast cancer. Public education and awareness is a key first step as any early detection program is unlikely to succeed unless the public is aware of the potential benefits. The effectiveness and efficiency of screening modalities including screening mammography, clinical breast examination (CBE) and breast self-examination (BSE) are reviewed in the context of resource availability and population-based need. While mammographic screening is the gold standard for early detection of breast cancer, considerations regarding cost-effectiveness and quality assurance of such a program in LMICs is a concern. The identification of a target group for mammography screening in LMICs should be based on the burden of disease in the population, the potential to benefit from screening, and available resources. Although there may be exceptions, in the absence of such information, the preponderance of the evidence suggests that in most countries it would be reasonable to begin a breast cancer screening program by offering mammography every 2 years to women between the ages of 50 and 65. Although two observational studies on BSE provide evidence that this screening modality reduces breast cancer mortality, this has not been confirmed in two randomized trials. Currently, the evidence is not sufficiently conclusive to justify the recommendation for routine CBE in population-based screening programs, because CBE has not been shown to independently decrease breast cancer mortality, although there are current trials to evaluate this modality. It is also important that any screening program be accompanied by the development of resources required for diagnosis and treatment. The success of any early detection program can be measured by cancer stage at diagnosis, and eventually improvement in survival.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):ED06-02.
Effect of Er,Cr:YSGG Laser and Professional Fluoride Application on Enamel Demineralization and on Fluoride Retention
Authors: Ana P.A. , Tabchoury C.P.M. , Cury J.A. , Zezell D.M.
Published: June 2012

This study evaluated the effect of Er,Cr:YSGG laser irradiation and professional fluoride application on enamel demineralization and on fluoride formation and retention. In a blind in vitro study, 264 human enamel slabs were distributed into 8 groups: G1 – untreated; G2 – treated with acidulated phosphate fluoride gel (APF gel, 1.23% F) for 4 min; G3, G4 and G5 – irradiated with Er,Cr:YSGG at 2.8, 5.6 and 8.5 J/cm2, respectively; G6, G7 and G8 – preirradiated with Er,Cr:YSGG at 2.8, 5.6 and 8.5 J/cm2, respectively, and subjected to APF gel application. Twenty slabs of each group were submitted to a pH-cycling regimen, and enamel demineralization was evaluated in 10 slabs of each group. In the other 10 slabs, CaF2-like material was determined. To evaluate F formed, 10 additional slabs of each group, not subjected to the pH cycling, were submitted to analysis of CaF2-like material and fluorapatite, while the other 3 slabs of each group were evaluated by scanning electron microscopy. The F content was also measured in all pH-cycling solutions. Laser at 8.5 J/cm2 and APF treatment reduced enamel demineralization compared to the control (p < 0.05), but the combination of these treatments was not more efficient than their isolated effect. A higher concentration of retained CaF2-like material was found in laser groups followed by APF in comparison with the APF gel treatment group. The findings suggest that laser treatment at 8.5 J/cm2 was able to decrease hardness loss, even though no additive effect with APF was observed. In addition, laser treatment increased the formation and retention of CaF2 on dental enamel.
Post-Treatment Change in the Localization of Recurrent or Persistent Macular Edema Secondary to Branch Retinal Vein Occlusion
Authors: Arima Mitsuru , Miyazaki Masanori , Arakawa Satoshi , Mochizuki Yasutaka , Ishibashi Tatsuro
Published: June 2012

Purpose: To investigate the change in localization of recurrent or persistent macular edema (ME) secondary to branch retinal vein occlusion (BRVO) after a therapeutic intervention. Methods: Twenty-six eyes of 23 patients with recurrent or persistent ME secondary to BRVO were included in this retrospective case series. We analyzed the distance between the fovea and the top of the ME (fovea–ME top distance) and the ME area using optical coherence tomography before treatment and when ME recurred or persisted. Results: The fovea–ME top distance decreased from 1.8 ± 1.6 to 1.2 ± 1.3 mm (p = 0.008). The ME area also decreased from 11.9 ± 4.9 to 7.6 ± 5.0 mm2 (p = 0.0003). The retinal vascular leakage area correlated with the ME area in all eyes. Conclusion: The site of recurrent or persistent ME tends to shift toward the fovea. These results suggest that residual perifoveal vascular leakage might be the predominant cause of recurrent or persistent ME.
Miscarriage after Sonographic Confirmation of an Ongoing Pregnancy in Women with Moderate and Severe Obesity
Authors: O’Dwyer Vicky , Monaghan Bernadette , Fattah Chro , Farah Nadine , Kennelly Mairead M. , Turner Michael J.
Published: June 2012

Objective: To compare the incidence of spontaneous miscarriage in women with moderate to severe obesity to that in women with a normal BMI after sonographic confirmation of the foetal heart rate in the first trimester. Methods: Women were enrolled in a prospective observational study at their convenience in the first trimester after an ultrasound confirmed an ongoing singleton pregnancy with foetal heart activity present. Maternal height and weight were measured digitally and BMI was calculated. Results: In the 3,000 women enrolled, the miscarriage rate overall was 3.9% (n = 117). The mean gestational age at enrolment was 11.1 weeks. In the class 2–3 (BMI > 34.9 kg/m2) obese primigravidas the miscarriage rate was 11.3% (n = 8) compared with 2.7% (n = 24) in the normal BMI category (p = 0.003), and 3.7% (n = 5) in the class 1 obese category (not significant). In multigravidas, there was no increased rate of miscarriage among class 2–3 obese women compared with multigravidas in the normal BMI category. The mean body composition values showed that primigravidas who miscarried had both increased fat and fat-free masses compared with those who did not, but multigravidas who miscarried had a similar fat mass and fat-free mass with those who did not. Conclusions: In women with sonographic evidence of foetal heart activity in the first trimester, the rate of spontaneous miscarriage is low. It was increased in moderate to severely obese primigravidas, but was not increased in other obese women compared to women in the normal BMI category.
Primary Pulmonary Choriocarcinoma: Case Report and Review of the Literature
Authors: Serno Julia , Zeppernick Felix , Jäkel Jörg , Schrading Simone , Maass Nicolai , Meinhold-Heerlein Ivo , Bauerschlag Dirk O.
Published: June 2012

Primary pulmonary choriocarcinoma is a rare disease with only 31 reported cases in the literature so far. Here, we summarize all published cases, including a recent case of our own clinic. Patients usually presented with symptoms like dyspnea, cough, chest pain, weight loss or hemoptysis. In some cases, the nodule in the lung was found in a routine check-up in asymptomatic patients. In the present case, the patient presented to our clinic because of a positive urine pregnancy test despite taking oral contraceptives. Patients in the analyzed cases were either treated with surgery, chemotherapy, radiotherapy or best supportive care. In the present case, a complete resection of the tumor was possible and the patient has not had any signs of recurrence so far. When looking at the published cases and corresponding outcomes, a slight tendency toward a complete resection followed by chemotherapy or close follow-up examinations seems to give the patients the best survival chances. Nevertheless, the overall prognosis of primary pulmonary choriocarinoma is poor and the 5-year survival rate is below 5%.
Expression of Sarcoglycans in the Human Cerebral Cortex: An Immunohistochemical and Molecular Study
Authors: Anastasi Giuseppe , Tomasello Francesco , Di Mauro Debora , Cutroneo Giuseppina , Favaloro Angelo , Conti Alfredo , Ruggeri Alessia , Rinaldi Carmela , Trimarchi Fabio
Published: June 2012

The sarcoglycan (SG) complex (SGC) is a subcomplex within the dystrophin-glycoprotein complex (DGC) and is composed of several transmembrane proteins (α, β, δ, γ, ε and ζ). The DGC supplies a transmembranous connection between the subsarcolemmal cytoskeleton networks and the basal lamina in order to protect the lipid bilayer and to provide a scaffold for signaling molecules in all muscle cells. In addition to its role in muscle tissue, dystrophin and some DGC components are expressed in neurons and glia. Very little is known about the SG subunits in the central nervous system (CNS) and some data suggested the presence of ε and ζ subunits only. In fact, mutations in the ε-SG gene cause myoclonus-dystonia, indicating its importance for brain function. To determine the presence and localization of SGC in the human cerebral cortex, we performed an investigation using immunofluorescence, immunoblotting and reverse transcriptase polymerase chain reaction. The results showed that all SG subunits are expressed in the human cerebral cortex, particularly in large neurons but also in astrocytes. These data suggest that the SG subcomplex may be involved in the organization of CNS synapses.
Correlation of Extracranial Internal Carotid Artery Tortuosity Index and Intraprocedural Complications during Carotid Artery Stenting
Authors: Wang Qizhang , Liu Chaolai , Yan Bernard , Fan Xiaobin , Zhang Min , Li Yongkun , Zhu Wusheng , Chen Maogang , Huang Xianjun , Zhang Zhizhong , Xu Gelin , Liu Xinfeng
Published: June 2012

Background: To investigate the correlation between tortuosity of extracranial internal carotid artery (EICA) and intraprocedural complications in patients undergoing carotid artery stenting (CAS). Methods: The study included 244 EICA in 223 patients undergoing CAS. Tortuosity in EICA was measured by the tortuosity index (TI). Multivariate logistic regression was performed to assess the independent risk factors of vasospasm during CAS. Receiver operating characteristic curve was performed to identify the cut-off of TI to predict vasospasm. Results: During the 244 CAS, 71 EICA presented vasospasm and 114 CAS presented hypotension. High TI, long procedural duration and female are independent risk factors for vasospasm during CAS. TI of 118 was the optimal cut-off to predict vasospasm during CAS (sensitivity: 85.9%, specificity: 78.6%). Linear regression analysis demonstrated that TI is positively correlated with procedural duration (p < 0.001). There was no significant difference in TI between the hypotension and non-hypotension groups (p = 0.145). Conclusion: TI is an independent risk factor for vasospasm during CAS and a TI ≥118 has the high sensitivity and specificity to predict vasospasm. Our results indicate the value of assessing tortuosity of EICA prior to choosing or performing the procedure in patients with carotid stenosis or occlusion.
Utility of Exhaled Breath Condensate pH for Diagnosing Occupational Asthma
Authors: Muñoz X. , Velasco M.I. , Culebras M. , Roca O. , Morell F. , Cruz M.J.
Published: June 2012

Introduction: The current reference standard method for diagnosing occupational asthma (OA) is specific inhalation challenge (SIC) with the suspected agent. The alternative method is serial peak expiratory flow (PEF) monitoring. Nevertheless, PEF does not have optimal sensitivity and specificity for this purpose. The aim of this study was to evaluate the utility of exhaled breath condensate (EBC) pH for the diagnosis of OA. Material and Methods: A prospective study was performed in 37 subjects with suspected OA. Serial PEF monitoring was carried out for 2 weeks at work and for 2 weeks off work. At the end of each period, the EBC pH and the methacholine concentration resulting in a 20% FEV1 decrease (PC20) were measured. SIC was subsequently performed. PEF graphs were interpreted visually by 3 experienced independent readers. Results: Seventeen patients tested positive with SIC. Receiver-operating characteristic curves showed that a decrease in EBC pH greater than 0.4 units during the period at work compared to the off-work period achieved the most satisfactory sensitivity (40%, CI 19.4–66.5) and specificity (90%, CI 66.9–98.2) for diagnosing OA. When EBC pH findings were added to PEF results, the diagnostic yield of PEF generally increased. Other test combinations (e.g. EBC pH plus PC20 or EBC pH plus PC20 plus PEF) did not improve diagnostic performance. Conclusions: Acidification of EBC pH at work and adding the EBC pH measurement to PEF monitoring during periods at work and off work may be useful for improving the diagnosis of OA.
Expression of Pannexin Isoforms in the Systemic Murine Arterial Network
Authors: Lohman Alexander W. , Billaud Marie , Straub Adam C. , Johnstone Scott R. , Best Angela K. , Lee Monica , Barr Kevin , Penuela Silvia , Laird Dale W. , Isakson Brant E.
Published: June 2012

Aims: Pannexins (Panx) form ATP release channels and it has been proposed that they play an important role in the regulation of vascular tone. However, distribution of Panx across the arterial vasculature is not documented. Methods: We tested antibodies against Panx1, Panx2 and Panx3 on human embryonic kidney cells (which do not endogenously express Panx proteins) transfected with plasmids encoding each Panx isoform and Panx1–/– mice. Each of the Panx antibodies was found to be specific and was tested on isolated arteries using immunocytochemistry. Results: We demonstrated that Panx1 is the primary isoform detected in the arterial network. In large arteries, Panx1 is primarily in endothelial cells, whereas in small arteries and arterioles it localizes primarily to the smooth muscle cells. Panx1 was the predominant isoform expressed in coronary arteries, except in arteries less than 100 µm where Panx3 became detectable. Only Panx3 was expressed in the juxtaglomerular apparatus and cortical arterioles. The pulmonary artery and alveoli had expression of all 3 Panx isoforms. No Panx isoforms were detected at the myoendothelial junctions. Conclusion: We conclude that the specific localized expression of Panx channels throughout the vasculature points towards an important role for these channels in regulating the release of ATP throughout the arterial network.
The Impact of Health and Financial Literacy on Decision Making in Community-Based Older Adults
Authors: James Bryan D. , Boyle Patricia A. , Bennett Jarred S. , Bennett David A.
Published: June 2012

Background: Health and financial literacy have been linked to the health and well-being of older adults, yet there are few data on how health and financial literacy actually impact decision making regarding healthcare and economic choices in advanced age. Objective: To examine the association of health and financial literacy with decision making in older adults. Method: Data came from 525 community-dwelling older persons without dementia from the Rush Memory and Aging Project, an ongoing longitudinal study of aging. Health and financial literacy were assessed via a series of questions designed to measure comprehension of health and financial information and concepts. The two scores were averaged to yield a total literacy score. A modified, 12-item version of the Decision-Making Competence Assessment Tool was used to measure financial and healthcare decision making (6 items each), using materials designed to approximate those used in real world settings. All 12 items were summed to yield a total decision-making score. Associations were tested via linear regression models adjusted for age, sex and education. Secondary models adjusted for global cognitive function, income, depression and chronic medical conditions. Results: On average, participants correctly answered 67% of the literacy questions (health literacy = 61.6%, SD = 18.8% and financial literacy = 72.5%, SD = 16.0%). After adjustment for cognitive function, the total literacy score was positively associated with the decision-making total score (estimate = 0.64, SE = 0.08, p < 0.001), as well as healthcare (estimate = 0.37, SE = 0.5, p < 0.001) and financial decision making (estimate = 0.28, SE = 0.05, p < 0.001). Further, total literacy, health and financial literacy all were independently associated with decision making in models adjusted for covariates including income, depression, and chronic medical conditions (all p values < 0.001). Finally, there was evidence of effect modification such that the beneficial association between literacy and healthcare decision making was stronger among older persons, poorer persons and persons at the lower ranges of cognitive ability. Conclusion: Among community based older persons without dementia, higher levels of health and financial literacy were associated with better decision making, suggesting that improvements in literacy could facilitate better decision making and lead to better health and quality of life in later years.
Hepatic Arterial Infusion with Tumor Necrosis Factor-α Induces Early Hepatic Hyperperfusion
Authors: Schäfer T. , Sperling J. , Slotta J.E. , Kollmar O. , Schilling M.K. , Menger M.D. , Richter S.
Published: June 2012

Background: Hepatic arterial infusion (HAI) has been developed for high-dose regional chemotherapy of unresectable liver metastases or primary liver malignancies. While it is well known that high concentrations of tumor necrosis factor (TNF)-α damage tumor blood perfusion, there is no information on whether autochthonous liver perfusion is affected by HAI with TNF-α. Therefore, we investigated the effects of HAI with TNF-α on hepatic macro- and microvascular perfusion. Methods: Swabian Hall pigs were randomized into three groups. HAI was performed with either 20 or 40 µg/kg body weight TNF-α (n = 6 each group). Saline-treated animals served as controls (n = 6). Analyses during a 2-hour post-HAI observation period included systemic hemodynamics, portal venous and hepatic arterial blood flow, portal venous pressure, and the blood flow in the hepatic microcirculation. Results: HAI with TNF-α caused a slight decrease of mean arterial blood pressure (p < 0.001), which was compensated by a moderate increase of heart rate (p < 0.001). No further systemic side effects of TNF-α were observed. HAI with TNF-α further caused a slight but not significant decrease of portal venous blood flow (p = 0.737) in both experimental groups, paralleled by an increase of hepatic arterial blood flow (p = 0.023, 20 µg/kg; p = 0.034, 40 µg/kg) resulting in an overall hepatic hyperperfusion. The hepatic hyperperfusion after HAI with 20 µg/kg TNF-α was more pronounced and associated with a 40% decrease of the blood flow in the hepatic microcirculation (p = 0.009). HAI with 40 µg/kg TNF-α was only associated with a temporary and moderate total hepatic hyperperfusion and did not affect the blood flow in the hepatic microcirculation. Conclusion: HAI with TNF-α causes a decrease of portal venous flow; however, this is overcompensated by an increased hepatic arterial blood flow, resulting in a total hepatic hyperperfusion. Moderate total hepatic hyperperfusion does not affect the blood flow in the hepatic microcirculation, while a persistent and more pronounced hyperperfusion may cause hepatic microcirculatory disturbances.
Shifts in the Microbial Population in Relation to in situ Caries Progression
Authors: Thomas R.Z. , Zijnge V. , Ciçek A. , de Soet J.J. , Harmsen H.J.M. , Huysmans M.C.D.N.J.M.
Published: June 2012

The shift in microbial diversity from young to mature plaque, related to caries activity on sound and restored surfaces, was studied using denaturing gradient gel electrophoresis. During a 20-week in situ study on caries progression 8 subjects wearing restored and unrestored dentin and enamel sections, biofilm was sampled after 1 and 20 weeks (young or mature plaque). A higher microbial diversity (mature plaque) was seen in caries-active compared to caries-free subjects. Rothia dentocariosa and Scardovia inopinata were absent from all caries-free sites, but appeared in 50% of the caries-active sites.
Prediction of Cardiovascular Events and All-Cause Mortality With Brachial-Ankle Elasticity Index
Authors: Vlachopoulos Charalambos , Aznaouridis Konstantinos , Terentes-Printzios Dimitrios , Ioakeimidis Nikolaos , Stefanadis Christodoulos
Published: June 2012

Brachial-ankle elasticity index (baEI; also known as brachial-ankle pulse wave velocity) has been proposed as a surrogate end point for cardiovascular disease. We performed a meta-analysis of longitudinal cohort studies for determining the ability of baEI to predict risk of cardiovascular events and all-cause mortality and dissecting factors influencing this predictive ability. Multiple online databases, reference lists from retrieved articles, and abstracts from international cardiovascular conventions were searched until April 2012. Longitudinal cohort studies that reported associations of baEI with clinical risk were included. Of the 18 studies included (8169 participants; mean follow-up, 3.6 years), 15 reported results on total cardiovascular events (5544 individuals), 7 on cardiovascular mortality (2274 individuals), and 9 on all-cause mortality (5097 individuals). The pooled relative risks for total cardiovascular events, cardiovascular mortality, and all-cause mortality were 2.95 (95% CI, 1.63–5.33), 5.36 (95% CI, 2.17–13.27), and 2.45 (95% CI, 1.56–3.86), respectively, for subjects with high versus low baEI (all
P
<0.001). An increase in baEI by 1 m/s corresponded with an increase of 12%, 13%, and 6% in total cardiovascular events, cardiovascular mortality, and all-cause mortality, respectively. We conclude that baEI is associated with increased risk of total cardiovascular events and all-cause mortality. Issues such as expansion of data to non-Asian populations, validation of path length estimation, determination of reference values, and prospective comparison with carotid-femoral pulse wave velocity remain to be resolved.
New Environmental Regionalism and Sustainable Development in the European Alps
Authors: Balsiger Jörg
Published: June 2012

In the context of increasing fragmentation and functional differentiation in international governance, new environmental regionalism represents a recent trend involving initiatives that seek to territorialize environmental governance at the level of transboundary ecoregions, such as mountain ranges or river basins. This article examines the implications of this trend for sustainable development, which is defined here as a procedural norm for reconciling the tradeoffs between environmental, economic, and social dimensions of wellbeing. This article (1) traces arguments concerning the origins of functional differentiation to research on European state-making; (2) offers two complementary perspectives that generate insights into sustainable development at the transboundary level, one focusing on the intersection of multiple and overlapping functional spaces, and the other focusing on regionalization as the domestic manifestation of regional themes; and (3) illustrates the significance of these perspectives in the case of the European Alps. The article suggests that the Alps serve both as the bounded object of an international legally binding agreement asking its signatories to formalize sustainable development, and as the intersection of multiple overlapping functional spaces. It lends support to claims about the link between rescaling and functional differentiation, but demonstrates that a sympathetic critique of new environmental regionalism need not conclude that the phenomenon exacerbates the fragmentation of international governance.
Navigating Regional Environmental Governance
Authors: Balsiger Jörg , VanDeveer Stacy D.
Published: June 2012

Global environmental governance is growing increasingly complex and recent scholarship and practice raise a number of questions about the continued feasibility of negotiating and implementing an ever-larger set of global environmental agreements. In the search for alternative conceptual models and normative orders, regional environmental governance (REG) is (re)emerging as a significant phenomenon in theory and practice. Although environmental cooperation has historically been more prevalent at the regional than at the global level, and has informed much of what we know today about international environmental cooperation, REG has been a neglected topic in the scholarly literature on international relations and international environmental politics. This introduction to the special issue situates theoretical arguments linked to REG in the broader literature, including the nature of regions, the location of regions in multilevel governance, and the normative arguments advanced for and against regional orders. It provides an overview of empirical work; offers quantitative evidence of REG's global distribution; advances a typology of REG for future research; and introduces the collection of research articles and commentaries through the lens of three themes: form and function, multilevel governance, and participation.
Frequency Selectivity Emerging from Spike-Timing-Dependent Plasticity
Authors: Gilson Matthieu , Bürck Moritz , Burkitt Anthony N. , van Hemmen J. Leo
Published: June 2012

Periodic neuronal activity has been observed in various areas of the brain, from lower sensory to higher cortical levels. Specific frequency components contained in this periodic activity can be identified by a neuronal circuit that behaves as a bandpass filter with given preferred frequency, or best modulation frequency (BMF). For BMFs typically ranging from 10 to 200 Hz, a plausible and minimal configuration consists of a single neuron with adjusted excitatory and inhibitory synaptic connections. The emergence, however, of such a neuronal circuitry is still unclear. In this letter, we demonstrate how spike-timing-dependent plasticity (STDP) can give rise to frequency-dependent learning, thus leading to an input selectivity that enables frequency identification. We use an in-depth mathematical analysis of the learning dynamics in a population of plastic inhibitory connections. These provide inhomogeneous postsynaptic responses that depend on their dendritic location. We find that synaptic delays play a crucial role in organizing the weight specialization induced by STDP. Under suitable conditions on the synaptic delays and postsynaptic potentials (PSPs), the BMF of a neuron after learning can match the training frequency. In particular, proximal (distal) synapses with shorter (longer) dendritic delay and somatically measured PSP time constants respond better to higher (lower) frequencies. As a result, the neuron will respond maximally to any stimulating frequency (in a given range) with which it has been trained in an unsupervised manner. The model predicts that synapses responding to a given BMF form clusters on dendritic branches.
Short-Term versus Climatological Relationship between Precipitation and Tropospheric Humidity
Authors: Masunaga Hirohiko
Published: June 2012

In this study the observed relationship of precipitation with column relative humidity (CRH), a metric of tropospheric humidity, is examined in order to address a known discrepancy inherent to past studies. A composite analysis of satellite data is carried out to explore the short-term (i.e., from hourly to daily) atmospheric variability for comparison with the climatology, hypothesizing that a primary cause for the discrepancy arises from a difference in the time scale of interest. The analysis is broken down into four classes on the basis of the degree of convective organization, ranging from unorganized shallow cumuli to highly organized convective systems. The CRH–precipitation relationship is found to be extremely nonlinear for the short-term variability, while the nonlinearity weakens to some degree when different convective systems in diverse humidity environments are averaged together into climatology. The weak exponential rise in the climatological CRH–precipitation curve occurs because highly organized convective systems become more frequent and intense and thus receive increasing weight in the climatological mean as the environment moistens.
A Bayes Factor Model for Detecting Artificial Discontinuities via Pairwise Comparisons
Authors: Zhang Jun , Zheng Wei , Menne Matthew J.
Published: June 2012

In this paper, the authors present a Bayes factor model for detecting undocumented artificial discontinuities in a network of temperature series. First, they generate multiple difference series for each station with the pairwise comparison approach. Next, they treat the detection problem as a Bayesian model selection problem and use Bayes factors to calculate the posterior probabilities of the discontinuities and estimate their locations in time and space. The model can be applied to large climate networks and realistic temperature series with missing data. The effectiveness of the model is illustrated with two realistic large-scale simulations and four sensitivity analyses. Results from applying the algorithm to observed monthly temperature data from the conterminous United States are also briefly discussed in the context of what is currently known about the nature of biases in the U.S. surface temperature record.
Comments on “Global and Regional Comparison of Daily 2-m and 1000-hPa Maximum and Minimum Temperatures in Three Global Reanalyses”
Authors: Brands S. , Gutiérrez J. M. , Cofiño A. S. , Herrera S.
Published: June 2012

Pitman and Perkins claimed that instantaneous 2-m air temperatures from different reanalysis products largely disagree over widespread regions of the globe and that, because of their much smaller differences, temperatures at 1000 hPa should be preferably used. This comment shows that this claim is based on erroneous results.