bluuebunny/crossref_metadata_2025 huggingface dataset:
New Frontiers inSchistosomaGenomics and Transcriptomics
Authors: Nahum Laila A. , Mourão Marina M. , Oliveira Guilherme
Published: November 2012

Schistosomes are digenean blood flukes of aves and mammals comprising 23 species. Some species are causative agents of human schistosomiasis, the second major neglected disease affecting over 230 million people worldwide. Modern technologies including the sequencing and characterization of nucleic acids and proteins have allowed large-scale analyses of parasites and hosts, opening new frontiers in biological research with potential biomedical and biotechnological applications. Nuclear genomes of the three most socioeconomically important species (S. haematobium,S. japonicum, andS. mansoni) have been sequenced and are under intense investigation. Mitochondrial genomes of sixSchistosomaspecies have also been completely sequenced and analysed from an evolutionary perspective. Furthermore, DNA barcoding of mitochondrial sequences is used for biodiversity assessment of schistosomes. Despite the efforts in the characterization ofSchistosomagenomes and transcriptomes, many questions regarding the biology and evolution of this important taxon remain unanswered. This paper aims to discuss some advances in the schistosome research with emphasis on genomics and transcriptomics. It also aims to discuss the main challenges of the current research and to point out some future directions in schistosome studies.
Depression and Anxiety Symptoms Relate to Distinct Components of Pain Experience among Patients with Breast Cancer
Authors: Galloway Sarah K. , Baker Megan , Giglio Pierre , Chin Steve , Madan Alok , Malcolm Robert , Serber Eva R. , Wedin Sharlene , Balliet Wendy , Borckardt Jeffrey
Published: November 2012

Breast cancer is a leading cancer diagnosis among women worldwide, with more than 210,000 new cases and 40,000 deaths per year in the United States. Pain, anxiety, and depression can be significant factors during the course of breast cancer. Pain is a complex experience with sensory, affective, and cognitive dimensions. While depression and anxiety symptoms are relatively common among breast cancer patients, little is known about the relation between these psychiatric factors and distinct components of the pain experience. In the present study 60 females presenting to an NCI-designated Cancer Center with newly diagnosed breast cancer completed the Center for Epidemiological Studies 10-item Depression Scale, the State Instrument of the Spielberger State-Trait Anxiety Inventory, and the McGill Pain Questionnaire. Findings indicate that anxiety and depression are common among newly diagnosed breast cancer patients; furthermore, patients experience an appreciable amount of pain even before oncologic treatment starts. State anxiety serves as a predictor of the sensory dimension of the pain experience, whereas depression serves as a predictor of the affective dimension of the pain experience.
A Novel Identification Method for Generalized T‐S Fuzzy Systems
Authors: Huang Ling , Wang Kai , Shi Peng , Karimi Hamid Reza
Published: November 2012

In order to approximate any nonlinear system, not just affine nonlinear systems, generalized T‐S fuzzy systems, where the control variables and the state variables, are all premise variables are introduced in the paper. Firstly, fuzzy spaces and rules were determined by using ant colony algorithm. Secondly, the state‐space model parameters are identified by using genetic algorithm. The simulation results show the effectiveness of the proposed algorithm.
Necrotizing Fasciitis of the Cervical Region following Extravasation Injury
Authors: Gündeşlioğlu Ayşe Özlem , Özen Emine Çiğdem
Published: November 2012

Necrotizing fasciitis is a rapidly progressive soft tissue infection that can cause local tissue destruction, necrosis, and life threatening severe sepsis. Necrotizing fasciitis in the head and neck region caused by an extravasation injury is rare. This paper reports a patient with necrotizing fasciitis of the cervical region caused by an extravasation injury which required an early surgical debridement.
Salinomycin as a Drug for Targeting Human Cancer Stem Cells
Authors: Naujokat Cord , Steinhart Roman
Published: November 2012

Cancer stem cells (CSCs) represent a subpopulation of tumor cells that possess self-renewal and tumor initiation capacity and the ability to give rise to the heterogenous lineages of malignant cells that comprise a tumor. CSCs possess multiple intrinsic mechanisms of resistance to chemotherapeutic drugs, novel tumor-targeted drugs, and radiation therapy, allowing them to survive standard cancer therapies and to initiate tumor recurrence and metastasis. Various molecular complexes and pathways that confer resistance and survival of CSCs, including expression of ATP-binding cassette (ABC) drug transporters, activation of the Wnt/β-catenin, Hedgehog, Notch and PI3K/Akt/mTOR signaling pathways, and acquisition of epithelial-mesenchymal transition (EMT), have been identified recently. Salinomycin, a polyether ionophore antibiotic isolated fromStreptomyces albus, has been shown to kill CSCs in different types of human cancers, most likely by interfering with ABC drug transporters, the Wnt/β-catenin signaling pathway, and other CSC pathways. Promising results from preclinical trials in human xenograft mice and a few clinical pilote studies reveal that salinomycin is able to effectively eliminate CSCs and to induce partial clinical regression of heavily pretreated and therapy-resistant cancers. The ability of salinomycin to kill both CSCs and therapy-resistant cancer cells may define the compound as a novel and an effective anticancer drug.
Macrophage Delivery of an Oncolytic Virus Abolishes Tumor Regrowth and Metastasis after Chemotherapy or Irradiation
Authors: Muthana Munitta , Rodrigues Samuel , Chen Yung-Yi , Welford Abigail , Hughes Russell , Tazzyman Simon , Essand Magnus , Morrow Fiona , Lewis Claire E.
Published: November 2012

Frontline anticancer therapies such as chemotherapy and irradiation often slow tumor growth, but tumor regrowth and spread to distant sites usually occurs after the conclusion of treatment. We recently showed that macrophages could be used to deliver large quantities of a hypoxia-regulated, prostate-specific oncolytic virus (OV) to prostate tumors. In the current study, we show that administration of such OV-armed macrophages 48 hours after chemotherapy (docetaxel) or tumor irradiation abolished the posttreatment regrowth of primary prostate tumors in mice and their spread to the lungs for up to 27 or 40 days, respectively. It also significantly increased the lifespan of tumor-bearing mice compared with those given docetaxel or irradiation alone. These new findings suggest that such a novel, macrophage-based virotherapy could be used to markedly increase the efficacy of chemotherapy and irradiation in patients with prostate cancer. Cancer Res; 73(2); 490–5. ©2012 AACR.
Competing Risks and Multistate Models
Authors: Schmoor Claudia , Schumacher Martin , Finke Jürgen , Beyersmann Jan
Published: November 2012

Complex clinical endpoints are present in studies in cancer. Especially in studies on hematopoietic stem-cell transplantation (HSCT), various risks exist after HSCT. Patients can experience acute and chronic graft versus host disease (GVHD) or need to undergo immunosuppressive therapy (IST), a relapse can occur, or patients can die after relapse or without former relapse (nonrelapse mortality, NRM). Sometimes, endpoints can be reasonably combined in a composite endpoint, as, for example, relapse and NRM are combined into disease-free survival (DFS). In this case, standard survival techniques, as Kaplan–Meier estimation of the DFS probability, can be applied.

Often, interest focuses on endpoints for which competing risks are present, as, for example, GVHD, with death without prior GVHD as competing risk. This results in a competing risks model, a special case of a multistate model. A more complex multistate model is required when the effects of events occurring in the course of the study on further disease process shall be investigated, as, for example, the effect of GVHD on relapse and NRM. Another endpoint of interest is time under IST. As patients usually experience multiple episodes of IST, thus switching back and forth between “IST” and “no IST” during follow-up, the multistate model used for analysis must be adapted for this event structure.

The aim of this nontechnical report is to explain use and interpretation of Cox-type regression models suitable for the different situations in a randomized trial on the effects of anti-T-cell globulin as GVHD prophylaxis. Clin Cancer Res; 19(1); 12–21. ©2012 AACR.
Memory Bias for Emotional and Illness-Related Words in Patients with Depression, Anxiety and Somatization Disorders: An Investigation with the Directed Forgetting Task
Authors: Wingenfeld Katja , Terfehr Kirsten , Meyer Björn , Löwe Bernd , Spitzer Carsten
Published: November 2012

Objective: Memory bias to emotion- and illness-related information plays a prominent role in many mental disorders, particularly major depressive disorder, anxiety disorders and somatoform disorder. The current study aimed to investigate memory bias in different mental disorders by using neutral, emotionally valenced and illness-related word stimuli in a directed forgetting task. Methods: Seventy-eight inpatients from a university-based psychosomatic hospital participated in the study. The item method of the directed forgetting task was used, in which participants are instructed to either forget or remember each item immediately after it has been presented. Memory performance was tested with a free recall test. Overall, 36 words were presented – 6 from each of 6 categories: neutral, negative, positive, illness related (‘somatoform’), depression related, and anxiety related. Three words of each category were to be remembered and 3 were to be forgotten. Results: Independently of the patients’ diagnoses, we found that most patients had relative difficulties remembering anxiety- and depression-related words, compared to neutral words, when they were instructed to remember them. By contrast, in the ‘instructed forgetting’ condition, patients showed deficits in the ability to forget illness-related stimuli relative to neutral material. These effects were unspecific with regard to diagnosis. Conclusions: The results in the ‘instructed remembering’ condition might be interpreted in the context of cognitive avoidance instead of a memory bias. In the ‘instructed forgetting’ condition, it appeared that illness-related words were more difficult to suppress compared to the other word types, which could explain the observed memory bias.
Mast Cell Tryptase Levels in Gut Mucosa in Patients with Gastrointestinal Symptoms Caused by Food Allergy
Authors: Hagel A.F. , deRossi T. , Zopf Y. , Konturek P. , Dauth W. , Kressel J. , Hahn E.G. , Raithel M.
Published: November 2012

Background and Aims: Mast cells, which are important effector cells in food allergy, require a special histologic treatment for quantification in endoscopic gastrointestinal samples. The objective of this study was to investigate whether mast cell tryptase (T), a typical mast cell-associated marker, may help to detect patients with food allergy. Methods: Mast cell T was investigated from 289 colorectal samples of 73 controls, 302 samples from 43 patients with food allergy and gastrointestinal symptoms, and 72 samples from 12 patients with partial or complete remission of allergic symptoms. Endoscopically taken samples were immediately put into liquid nitrogen, mechanically homogenized by a micro-dismembrator with three homogenization steps and tissue T content (ng T/mg wet weight) was measured by fluoroenzyme immunoassay. Results: Tissue T levels from the lower gastrointestinal tract were significantly elevated (p < 0.0001) in patients with manifest gastrointestinal allergy (median: 55.7, range: 9.3–525.0) compared with controls (median: 33.5, range: 8.0–154.6). A subgroup of 12 patients with remission of allergy showed markedly decreased symptom scores and mucosal T levels after more than 1 year of antiallergic therapy (pretreatment median: 54.1, range: 37.0–525.0 and posttreatment median: 28.4, range: 19.8–69.1; p = 0.01). Conclusions: High T levels in the gut of food-allergic patients support the role of stimulated mast cells or an increased mast cell number.
Efficacy of Chemotherapy for Advanced Non-Small Cell Lung Cancer with Idiopathic Pulmonary Fibrosis
Authors: Watanabe Naohiro , Taniguchi Hiroyuki , Kondoh Yasuhiro , Kimura Tomoki , Kataoka Kensuke , Nishiyama Osamu , Kondo Masashi , Hasegawa Yoshinori
Published: November 2012

Background: Idiopathic pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonia and is associated with an independent increased risk of lung carcinogenesis. The benefit of chemotherapy for lung cancer in cases of IPF remains unknown. Objectives: This study was conducted to elucidate the efficacy of chemotherapy for advanced non-small cell lung cancer (NSCLC) in patients with IPF. Methods: Advanced (i.e. stage IIIB and IV) NSCLC patients with IPF who received systemic chemotherapy were studied. Response rate, toxicity, overall survival and progression-free survival were investigated. Results: Between January 2000 and December 2009, 21 patients were enrolled in this study and treated with chemotherapy. The overall response rate with the 1st regimen was 42.9%. The median overall survival was 11.4 months, the 1-year survival rate was 28.6% and the median PFS was 5.4 months. Conclusions: This study showed that advanced NSCLC patients with IPF may benefit from chemotherapy; well-controlled studies are still needed to clarify the efficacy.
Cytokine Biomarker Candidates in Breast Milk Associated with the Development of Atopic Dermatitis in 6-Month-Old Infants
Authors: Ochiai Shingo , Shimojo Naoki , Morita Yoshinori , Tomiita Minako , Arima Takayasu , Inoue Yuzaburo , Nakaya Mayuko , Uehara Naoki , Sato Yasunori , Mori Chisato , Suzuki Yoichi , Kohno Yoichi
Published: November 2012

Background: A few studies have reported that the quantity of selected cytokines/chemokines in breast milk might be associated with atopic dermatitis (AD). Using the multiplex cytokine assay system, we examined cytokines/chemokines in human milk in order to identify new biomarkers related to AD. Methods: We recruited 49 infants with or without AD who participated in a birth cohort and measured the concentrations of cytokines/chemokines in the colostrum (collected within 4–5 days after birth) and mature milk (collected at 1 month postpartum) received by the infants. Results: There were significant differences in the concentrations of interleukin (IL)-1β and IL-12p40 in the colostrum, and in those of IL-4, eotaxin, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-α2 and MIP-1α in the mature milk between the milk received by infants who developed AD at the age of 6 months and that received by the control infants. There was weak to moderate correlation between those 6 cytokines/chemokines in mature milk. Atopic history and IgE levels of mothers were not related to cytokine/chemokine concentrations in breast milk. Logistic regression analyses showed that high levels of eotaxin in the mature milk were a risk for the development of AD at 6 months of age. Conclusion: These results suggest that several cytokines/chemokines, especially eotaxin, are potential biomarkers for development of AD in early infancy.
Urokinase Receptor Mediates Doxorubicin-Induced Vascular Smooth Muscle Cell Senescence via Proteasomal Degradation of TRF2
Authors: Hodjat Mahshid , Haller Hermann , Dumler Inna , Kiyan Yulia
Published: November 2012

The anthracycline doxorubicin is a widely used effective anti-cancer drug. However, its application and dosage are severely limited due to its cardiotoxicity. The exact mechanisms of doxorubicin-induced cardiotoxic side effects remain poorly understood. Even less is known about the impact of doxorubicin treatment on vascular damage. We found that low doses of doxorubicin induced a senescent response in human primary vascular smooth muscle cells (VSMC). We observed that expression of urokinase receptor (uPAR) was upregulated in response to doxorubicin. Furthermore, the level of uPAR expression played a decisive role in developing doxorubicin-induced senescence. uPAR silencing in human VSMC by means of RNA interference as well as uPAR knockout in mouse VSMC resulted in abrogation of doxorubicin-induced cellular senescence. On the contrary, uPAR overexpression promoted VSMC senescence. We further found that proteasomal degradation of telomeric repeat binding factor 2 (TRF2) mediates doxorubicin-induced VSMC senescence. Our results demonstrate that uPAR controls the ubiquitin-proteasome system in VSMC and regulates doxorubicin-induced TRF2 ubiquitination and proteasomal degradation via this mechanism. Therefore, VSMC senescence induced by low doses of doxorubicin may contribute to vascular damage upon doxorubicin treatment. uPAR-mediated TRF2 ubiquitination and proteasomal degradation are further identified as a molecular mechanism underlying this process.
A History of the Isolation and Identification of Vitamin B6
Authors: Rosenberg Irwin H.
Published: November 2012

In the 1930s, Rudolf Peters showed that young rats kept on a semi-synthetic diet with added thiamin and riboflavin but no other supplement developed ‘rat acrodynia’, a condition characterized by severe cutaneous lesions. In 1934, Paul György showed that the factor which cured ‘rat acrodynia’ was vitamin B6. Other studies soon showed that vitamin B6 deficiency produced convulsions in rats, pigs, and dogs, and a microcytic anemia in certain animals. Samuel Lepkovsky isolated and crystallized vitamin B6 in 1938. The following year, Leslie Harris and Karl Folkers, and Richard Kuhn and his associates independently showed that vitamin B6 was a pyridine derivative, 3-hydroxy-4,5-dihydroxy-methyl-2-methyl-pyridine. György proposed the term pyridoxine for this derivative. Esmond Snell developed a microbiological growth assay in 1942 that led to the characterization of pyridoxamine, the animated product of pyridoxine, and pyridoxal, the formyl derivative of pyridoxine. Further studies showed that pyridoxal, pyridoxamine, and pyridoxine have largely equal activity in animals and owe their vitamin activity to the ability of the organism to convert them into the enzymatically active form pyridoxal-5-phosphate. Pyridoxal-5-phosphate plays a role in a wide variety of enzyme systems, especially in the metabolic utilization and transformation of amino acids.
The Discovery of Vitamin C
Authors: Carpenter Kenneth J.
Published: November 2012

The term ‘scurvy’ for the disease resulting from prolonged vitamin C deficiency had origins in ‘scorbutus’ (Latin), ‘scorbut’ (French), and ‘Skorbut’ (German). Scurvy was a common problem in the world’s navies and is estimated to have affected 2 million sailors. In 1747, James Lind conducted a trial of six different treatments for 12 sailors with scurvy: only oranges and lemons were effective in treating scurvy. Scurvy also occurred on land, as many cases occurred with the ‘great potato famine’ in Ireland in 1845. Many animals, unlike humans, can synthesize their own vitamin C. Axel Holst and Theodor Frölich fortuitously produced scurvy in the guinea pig, which like humans requires vitamin C in the diet. In 1928, Albert Szent-Györgyi isolated a substance from adrenal glands that he called ‘hexuronic acid’. Four years later, Charles Glen King isolated vitamin C in his laboratory and concluded that it was the same as ‘hexuronic acid’. Norman Haworth deduced the chemical structure of vitamin C in 1933.
Pig Kidney Transplantation: An Up-To-Date Guideline
Authors: Golriz M. , Fonouni H. , Nickkholgh A. , Hafezi M. , Garoussi C. , Mehrabi A.
Published: November 2012

Background: Swine and human beings have many aspects in common that make swine a well-characterized large animal model for kidney transplantation (KTx). However, pigs have some peculiar anatomical characteristics that standardized techniques must adapt to. The aim of this study was to prepare an up-to-date guideline for porcine KTx. Methods: To achieve this goal, we performed a Medline search using the terminology ‘kidney’ or ‘renal’ and ‘transplantation’ and ‘pig’ or ‘swine’ or ‘porcine’. We found over 1,300 published articles since 1963. Only 13 studies focused on the surgical aspect. Furthermore, we reviewed related books and articles about swine anatomical characteristics and surgery. Finally, our experimental experiences of KTx during the last few decades were added to this collection. Results: Proper hosting, fasting, anesthesia, medical therapy and monitoring can prevent postoperative complications. Explantation with a Carrel patch of the aorta facilitates the implantation and prevents future stenosis. Native nephrectomy makes the follow-up of the implanted organ more precise. KTx in the infrarenal fossa via end-to-side anastomosis to the aorta and inferior vena cava followed by ureteroureterostomy are the recommended options for KTx in pigs compared to other possible methods. Conclusion: Pigs, with respect to their characterizations, constitute one of the best large animal models for KTx. Preoperative preparations are as important as the intra- and postoperative management. Using the most adaptable methods of surgery with respect to the specific anatomical characteristics of pigs can prevent undermining the studies and avoid preventable complications and pitfalls.
Premature Aging of the Microcirculation in Patients with Advanced Chronic Kidney Disease
Authors: Thang Oanh H.D. , Serné Erik H. , Grooteman Muriel P.C. , Smulders Yvo M. , ter Wee Piet M. , Tangelder Geert-Jan , Nubé Menso J.
Published: November 2012

Background: Increasing age and advanced chronic kidney disease (CKD) are both associated with an attenuated vasodilator response of the skin microcirculation. In the present study, we investigated the effect of aging on microvascular reactivity in patients with advanced CKD. Methods: Acetylcholine (ACh)-mediated endothelium-dependent vasodilation and sodium nitroprusside (SNP)-mediated endothelium-independent vasodilation were assessed by iontophoresis combined with laser Doppler flowmetry. Microvascular function was compared between 52 patients with advanced CKD (stage 4–5: n = 16; end-stage renal disease: n = 36) and 33 healthy control subjects. As aging has an important effect on microvascular function, both control subjects and CKD patients were divided in subgroups younger and older than 45 years. Linear regression analysis was applied to assess potential associations between microvascular function and various demographic and clinical parameters. Results: There were three main findings. (1) In young patients with advanced CKD, both ACh- and SNP-mediated vasodilations were impaired if compared to young healthy controls (p = 0.04 and p = 0.056, respectively). (2) In young patients with advanced CKD, microvascular function was similar to old healthy controls and elderly patients with advanced CKD. (3) Whereas age was inversely associated with microvascular function in healthy controls (log ACh-mediated vasodilation R = –0.41; p = 0.02 and log SNP-mediated vasodilation R = –0.38; p = 0.03), no such relation was found in patients with advanced CKD. Conclusions: Our results are consistent with premature aging of the microvascular vasodilatory capacity in patients with advanced CKD.
Systematic Review and Meta-Analysis of Combination Therapy with Cholinesterase Inhibitors and Memantine in Alzheimer’s Disease and Other Dementias
Authors: Muayqil Taim , Camicioli Richard
Published: November 2012

Background:N-methyl-D-aspartic acid antagonists (memantine) and cholinesterase inhibitors (ChEIs) are the only two approved classes of drugs to treat dementia; this paper explores the evidence for using these two treatments in combination. Objective: To determine the efficacy and safety of using combination therapy with memantine and a ChEI to treat dementia in comparison to monotherapy with either memantine or a ChEI. Methods: In March 2012, we systematically searched MEDLINE/PubMed, EMBASE, Cochrane library, and grey literature databases. All study types were included, except for case series or reports, which looked at combination therapy versus monotherapy in various dementing disorders. Data was pooled for blinded randomized controlled trials (RCTs) only; mean differences and standardized mean differences were used to determine effect sizes. Results: Thirteen studies were included in this review; 3 were blinded RCTs, with a total of 971 Alzheimer’s disease (AD) patients, which were included into the meta-analysis. No papers were found that primarily addressed combination therapy in other dementias. In the meta-analysis, small but statistically significant effect sizes were seen in favor of combination therapy among patients with moderate to severe AD on the scales of cognition (0.45–0.52; p < 0.0001), scales of functional outcomes (0.23–0.3; p < 0.01), and the neuropsychiatric inventory (3.7–4.4; p < 0.0001). Among the open-label studies, 3 out of 6 suggested benefits, as did the 4 included cohort studies. However, the high risk of bias encountered in the latter two study designs limits deducing any conclusions about benefit. Conclusion: Although there were statistically significant changes in favor of combination therapy in moderate to severe AD, heterogeneity in scales and patient characteristics exists. However, it is unclear if clinically significant outcomes can be achieved using the combination therapy. More studies are required before a recommendation for combination therapy can be made.
Strategies to Query and Display Allergy-Derived Epitope Data from the Immune Epitope Database
Authors: Vaughan Kerrie , Peters Bjoern , Larche Mark , Pomes Anna , Broide David , Sette Alessandro
Published: November 2012

The recognition of specific epitopes on allergens by antibodies and T cells is a key element in allergic processes. Analysis of epitope data may be of interest for basic immunopathology or for potential application in diagnostics or immunotherapy. The Immune Epitope Database (IEDB) is a freely available repository of epitope data from infectious disease agents, as well as epitopes defined for allergy, autoimmunity, and transplantation. The IEDB curates the experiments associated with each epitope and thus provides a variety of different ways to search the data. This review aims to demonstrate the utility of the IEDB and its query strategies, including searching by epitope structure (peptidic/nonpeptidic), by assay methodology, by host, by the allergen itself, or by the organism from which the allergen was derived. Links to tools for visualization of 3-D structures, epitope prediction, and analyses of B and T cell reactivity by host response frequency score are also highlighted.
Oxytocin Affects Nitric Oxide and Cytokine Production by Sepsis-Sensitized Macrophages
Authors: Oliveira-Pelegrin Gabriela Ravanelli , Saia Rafael Simone , Cárnio Evelin Capellari , Rocha Maria José Alves
Published: November 2012

Background/Aim: Oxytocin (OXT) secretion during cecal ligation puncture (CLP)-induced sepsis has not yet been examined. Although immune properties have been attributed to OXT, its effect on CLP-sensitized macrophages has never been investigated. We analyzed OXT secretion during CLP and its effect in CLP-sensitized macrophage cultures. Methods: Male Wistar rats were decapitated 4, 6 or 24 h after CLP surgery or sham operation and blood, brain and neurohypophyses were collected for OXT measurements. In another set of animals we studied the effect of OXT on nitrite, tumor necrosis factor (TNF-α), interleukin (IL)-1β and IL-10 production of peritoneal macrophages harvested at 6 and 24 h after CLP. Results: In the early phase of sepsis (4–6 h), OXT levels increased in plasma and decreased in hypothalamus and neurohypophysis. In the late phase (24 h), plasma and neurohypophyseal levels remained basal. In the paraventricular, the OXT content remained low, but in the supraoptic increased. Macrophages of the early phase of sepsis pretreated with OXT and stimulated with lipopolysaccharide showed decreased nitrite, TNF-α and IL-1β levels, but no alteration in IL-10 production. In the late phase, they showed reduction only on IL-1β. Conclusions: OXT secretion during sepsis may represent a neuroendocrine response contributing to the overall host response to infection by decreasing the proinflammatory response and oxidative stress.
Relationship between Body Mass Index and Mortality in Hemodialysis Patients: A Meta-Analysis
Authors: Jialin Wang , Yi Zhou , Weijie Yuan
Published: November 2012

Background: Previous studies have reported that reduced mortality rates in hemodialysis (HD) patients were negatively related to body mass index (BMI). The potentially protective effect of increased BMI in HD patients has been referred to as ‘reverse epidemiology’. Our meta-analysis was conducted to examine the relationship between different BMI ranges and mortality in HD patients. Methods: Eligible studies assessing the effects of BMI ranges on all-cause mortality (published from 1966 to February 2012) were searched, using ‘hemodialysis’ or ‘haemodialysis’ and ‘obese’ or ‘body mass index’ or ‘overweight’ as key words, in combination with ‘mortality’, ‘survival’, ‘reverse epidemiology’ and ‘obesity paradox’. Inclusion criteria were that trials reported mortality in HD patients according to the traditional World Health Organization/National Institutes of Health BMI classification, and BMI levels are acceptable within 2 index points. The quality of the trials was evaluated using the risk of bias assessment in studies included in Cochrane reviews. The mortality rates in HD patients were the primary end point of the study. With no significant heterogeneity, a fixed-effects model was used for analyses. Results: Four studies with a total of 81,423 patients met final inclusion criteria. Compared to individuals with non-elevated BMI, those with elevated BMI (BMI ≥25, OR 0.67, 95% CI 0.65–0.68) had a lower all-cause mortality. In a risk-adjusted sensitivity analysis, elevated BMI levels (adjusted hazard ratio 0.94, 95% CI 0.92–0.96) remained protective against mortality. Conclusion: High BMI levels were associated with lower all-cause mortality rates in HD patients. It is possible that more stable hemodynamic status, cytokine and neurohormonal alternations contribute to the protective effects of BMI on mortality in HD patients. There is a need for prospective studies to elucidate mechanisms behind this relationship.
Mitogen-Activated Protein Kinase 14 Is a Novel Negative Regulatory Switch for the Vascular Smooth Muscle Cell Contractile Gene Program
Authors: Long Xiaochun , Cowan Sarah L. , Miano Joseph M.
Published: November 2012

Objective—

Several studies have shown through chemical inhibitors that p38 mitogen-activated protein kinase (MAPK) promotes vascular smooth muscle cell (VSMC) differentiation. Here, we evaluate the effects of knocking down a dominant p38MAPK isoform on VSMC differentiation.

Methods and Results—

Knockdown of p38MAPKα (
MAPK14
) in human coronary artery SMCs unexpectedly increases VSMC differentiation genes, such as
miR145
,
ACTA2
,
CNN1
,
LMOD1
, and
TAGLN
, with little change in the expression of serum response factor (SRF) and 2 SRF cofactors, myocardin (
MYOCD
) and myocardin-related transcription factor A (
MKL1
). A variety of chemical and biological inhibitors demonstrate a critical role for a RhoA-MKL1-SRF–dependent pathway in mediating these effects. MAPK14 knockdown promotes MKL1 nuclear localization and VSMC marker expression, an effect partially reversed with Y27632; in contrast, MAP2K6 (MKK6) blocks MKL1 nuclear import and VSMC marker expression. Immunostaining and Western blotting of injured mouse carotid arteries reveal elevated MAPK14 (both total and phosphorylated) and reduced VSMC marker expression.

Conclusion—

Reduced MAPK14 expression evokes unanticipated increases in VSMC contractile genes, suggesting an unrecognized negative regulatory role for MAPK14 signaling in VSMC differentiation.
Effects of Postmenopausal Hormone Therapy on Incident Atrial Fibrillation
Authors: Perez Marco V. , Wang Paul J. , Larson Joseph C. , Virnig Beth A. , Cochrane Barbara , Curb J. David , Klein Liviu , Manson JoAnn E. , Martin Lisa W. , Robinson Jennifer , Wassertheil-Smoller Sylvia , Stefanick Marcia L.
Published: November 2012

Background—

Atrial fibrillation (AF) is less prevalent in women versus men, but associated with higher risks of stroke and death in women. The role hormone therapy plays in AF is not well understood.

Methods and Results—

The Women’s Health Initiative randomized postmenopausal women to placebo or conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) if they had a uterus (N=16 608) or to conjugated equine estrogens only if they had prior hysterectomy (N=10 739). Incident AF was identified by ECG and diagnosis codes from Medicare claims or hospitalization records. Hazard ratios for incident AF were estimated using Cox proportional hazards regression. After excluding participants with baseline AF, there were 611 incident AF cases over a mean of 5.6 years among 16 128 estrogen plus progestin participants, and 683 cases over a mean of 7.1 years among 10 251 conjugated equine estrogens alone participants. Incident AF was more frequent in the active groups of both trials, reaching statistical significance in the trial of conjugated equine estrogens alone in women with prior hysterectomy (hazard ratio, 1.17; CI, 1.00–1.36;
P
=0.045) and in the pooled analysis (hazard ratio, 1.12; CI, 1.00–1.24;
P
=0.05), but not in the estrogen plus progestin trial (hazard ratio, 1.07; CI, 0.91–1.25;
P
=0.44). These results were only minimally affected by adjustment for incident stroke, coronary heart disease, and heart failure.

Conclusions—

Incident AF was modestly elevated in hysterectomized women randomized to postmenopausal E-alone, and in the pooled group randomized to E-alone or estrogen plus progestin. The trend in women with intact uterus receiving estrogen plus progestin, considered separately, was not statistically significant.
Myosin Phosphatase Modulates the Cardiac Cell Fate by Regulating the Subcellular Localization of Nkx2.5 in a Wnt/Rho–Associated Protein Kinase–Dependent Pathway
Authors: Ryan Tammy , Shelton Michael , Lambert Jean-Philippe , Malecova Barbora , Boisvenue Sophie , Ruel Marc , Figeys Daniel , Puri Pier Lorenzo , Skerjanc Ilona S.
Published: November 2012

Rationale:

Nkx2.5 is a transcription factor that regulates cardiomyogenesis in vivo and in embryonic stem cells. It is also a common target in congenital heart disease. Although Nkx2.5 has been implicated in the regulation of many cellular processes that ultimately contribute to cardiomyogenesis and morphogenesis of the mature heart, relatively little is known about how it is regulated at a functional level.

Objective:

We have undertaken a proteomic screen to identify novel binding partners of Nkx2.5 during cardiomyogenic differentiation in an effort to better understand the regulation of its transcriptional activity.

Methods and Results:

Purification of Nkx2.5 from differentiating cells identified the myosin phosphatase subunits protein phosphatase 1β and myosin phosphatase targeting subunit 1 (Mypt1) as novel binding partners. The interaction with protein phosphatase 1 β/Mypt1 resulted in exclusion of Nkx2.5 from the nucleus and, consequently, inhibition of its transcriptional activity. Exclusion of Nkx2.5 was inhibited by treatment with leptomycin B and was dependent on an Mypt1 nuclear export signal. Furthermore, in transient transfection experiments, Nkx2.5 colocalized outside the nucleus with phosphorylated Mypt1 in a manner dependent on Wnt signaling and Rho-associated protein kinase. Treatment of differentiating mouse embryonic stem cells with Wnt3a resulted in enhanced phosphorylation of endogenous Mypt1, increased nuclear exclusion of endogenous Nkx2.5, and a failure to undergo terminal cardiomyogenesis. Finally, knockdown of Mypt1 resulted in rescue of Wnt3a-mediated inhibition of cardiomyogenesis, indicating that Mypt1 is required for this process.

Conclusions:

We have identified a novel interaction between Nkx2.5 and myosin phosphatase. Promoting this interaction represents a novel mechanism whereby Wnt3a regulates Nkx2.5 and inhibits cardiomyogenesis.
Low Serum Magnesium and the Development of Atrial Fibrillation in the Community
Authors: Khan Abigail May , Lubitz Steven A. , Sullivan Lisa M. , Sun Jenny X. , Levy Daniel , Vasan Ramachandran S. , Magnani Jared W. , Ellinor Patrick T. , Benjamin Emelia J. , Wang Thomas J.
Published: November 2012

Background—

Low serum magnesium has been linked to increased risk of atrial fibrillation (AF) after cardiac surgery. It is unknown whether hypomagnesemia predisposes to AF in the community.

Methods and Results—

We studied 3530 participants (mean age, 44 years; 52% women) from the Framingham Offspring Study who attended a routine examination and were free of AF and cardiovascular disease. We used Cox proportional hazard regression analysis to examine the association between serum magnesium at baseline and risk of incident AF. Analyses were adjusted for conventional AF risk factors, use of antihypertensive medications, and serum potassium. During up to 20 years of follow-up, 228 participants developed AF. Mean serum magnesium was 1.88 mg/dL. The age- and sex-adjusted incidence rate of AF was 9.4 per 1000 person-years (95% confidence interval, 6.7–11.9) in the lowest quartile of serum magnesium (≤1.77 mg/dL) compared with 6.3 per 1000 person-years (95% confidence interval, 4.1–8.4) in the highest quartile (≥1.99 mg/dL). In multivariable-adjusted models, individuals in the lowest quartile of serum magnesium were ~50% more likely to develop AF (adjusted hazard ratio, 1.52; 95% confidence interval, 1.00–2.31;
P
=0.05) compared with those in the upper quartiles. Results were similar after the exclusion of individuals on diuretics.

Conclusions—

Low serum magnesium is moderately associated with the development of AF in individuals without cardiovascular disease. Because hypomagnesemia is common in the general population, a link with AF may have potential clinical implications. Further studies are warranted to confirm our findings and to elucidate the underlying mechanisms.
Pivotal Role of Rho-Associated Kinase 2 in Generating the Intrinsic Circadian Rhythm of Vascular Contractility
Authors: Saito Toshiro , Hirano Mayumi , Ide Tomomi , Ichiki Toshihiro , Koibuchi Noriyuki , Sunagawa Kenji , Hirano Katsuya
Published: November 2012

Background—

The circadian variation in the incidence of cardiovascular events may be attributable to the circadian changes in vascular contractility. The circadian rhythm of vascular contractility is determined by the interplay between the central and peripheral clocks. However, the molecular mechanism of the vascular intrinsic clock that generates the circadian rhythm of vascular contractility still remains largely unknown.

Methods and Results—

The agonist-induced phosphorylation of myosin light chain in cultured smooth muscle cells synchronized by dexamethasone pulse treatment exhibited an apparent circadian oscillation, with a 25.4-hour cycle length. The pharmacological inhibition and knockdown of Rho-associated kinase 2 (ROCK2) abolished the circadian rhythm of myosin light chain phosphorylation. The expression and activity of ROCK2 exhibited a circadian rhythm in phase with that of myosin light chain phosphorylation. A clock gene, RORα, activated the promoter of the ROCK2 gene, whereas its knockdown abolished the rhythmic expression of ROCK2. In the mouse aorta, ROCK2 expression exhibited the circadian oscillation, with a peak at Zeitgeber time 0/24 and a nadir at Zeitgeber time 12. The myofilament Ca
2+
sensitization induced by GTPγS and U46619, a thromboxane A2 analog, at Zeitgeber time 0/24 was greater than that seen at Zeitgeber time 12. The circadian rhythm of ROCK2 expression and myofilament Ca
2+
sensitivity was abolished in
staggerer
mutant mice, which lack a functional RORα.

Conclusions—

ROCK2 plays a pivotal role in generating the intrinsic circadian rhythm of vascular contractility by receiving a cue from RORα. The ROCK2-mediated intrinsic rhythm of vascular contractility may underlie the diurnal variation of the incidence of cardiovascular diseases.
Nationalism and the Nature of Thoreau's “Walking”
Authors: Menard Andrew
Published: November 2012

The author argues that “Walking” is an essay on nationalism. Subverting Americans’ admiration for the settled countryside of England, Thoreau derived this nationalism from the sinks and swamps symbolized by “the Wild” and “the West.” But he resisted the lure of Manifest Destiny by looking to the localism of a natural community.
A Multisensor Perspective on the Radiative Impacts of Clouds and Aerosols
Authors: Henderson David S. , L’Ecuyer Tristan , Stephens Graeme , Partain Phil , Sekiguchi Miho
Published: November 2012

The launch of CloudSat and Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) in 2006 provided the first opportunity to incorporate information about the vertical distribution of cloud and aerosols directly into global estimates of atmospheric radiative heating. Vertical profiles of radar and lidar backscatter from CloudSat’s Cloud Profiling Radar (CPR) and the Cloud–Aerosol Lidar with Orthogonal Polarization (CALIOP) aboard CALIPSO naturally complement Moderate Resolution Imaging Spectroradiometer (MODIS) radiance measurements, providing a nearly complete depiction of the cloud and aerosol properties that are essential for deriving high-vertical-resolution profiles of longwave (LW) and shortwave (SW) radiative fluxes and heating rates throughout the atmosphere. This study describes a new approach for combining vertical cloud and aerosol information from CloudSat and CALIPSO with MODIS data to assess impacts of clouds and aerosols on top-of-atmosphere (TOA) and surface radiative fluxes. The resulting multisensor cloud–aerosol product is used to document seasonal and annual mean distributions of cloud and aerosol forcing globally from June 2006 through April 2011. Direct comparisons with Clouds and the Earth’s Radiant Energy System (CERES) TOA fluxes exhibit a close correlation, with improved errors relative to CloudSat-only products. Sensitivity studies suggest that remaining uncertainties in SW fluxes are dominated by uncertainties in CloudSat liquid water content estimates and that the largest sources of LW flux uncertainty are prescribed surface temperature and lower-tropospheric humidity. Globally and annually averaged net TOA cloud radiative effect is found to be −18.1 W m−2. The global, annual mean aerosol direct radiative effect is found to be −1.6 ± 0.5 W m−2 (−2.5 ± 0.8 W m−2 if only clear skies over the ocean are considered), which, surprisingly, is more consistent with past modeling studies than with observational estimates that were based on passive sensors.
Feasibility of High-Density Climate Reconstruction Based on Forest Inventory and Analysis (FIA) Collected Tree-Ring Data
Authors: DeRose R. Justin , Wang Shih-Yu , Shaw John D.
Published: November 2012

This study introduces a novel tree-ring dataset, with unparalleled spatial density, for use as a climate proxy. Ancillary Douglas fir and piñon pine tree-ring data collected by the U.S. Forest Service Forest Inventory and Analysis Program (FIA data) were subjected to a series of tests to determine their feasibility as climate proxies. First, temporal coherence between the FIA data and previously published tree-ring chronologies was found to be significant. Second, spatial and temporal coherence between the FIA data and water year precipitation was strong. Third, the FIA data captured the El Niño–Southern Oscillation dipole and revealed considerable latitudinal fluctuation over the past three centuries. Finally, the FIA data confirmed the quadrature-phase coupling between wet/dry cycles and Pacific decadal variability known to exist for the Intermountain West. The results highlight the possibility of further developing high-spatial-resolution climate proxy datasets for the western United States. (The preliminary FIA data are provided online at http://cliserv.jql.usu.edu/FIAdata/ in both station and gridded format.)
Considering the Needs of English Language Learner Populations
Authors: Moore Brooke A. , Klingner Janette K.
Published: November 2012

This article synthesizes reading intervention research studies intended for use with struggling or at-risk students to determine which studies adequately address population validity, particularly in regard to the diverse reading needs of English language learners. An extensive search of the professional literature between 2001 and 2010 yielded a total of 67 reading intervention studies targeting at-risk elementary students. Findings revealed that many current research studies fail to adequately describe the sample, including the accessible and target populations, and to disaggregate their findings based on demographic characteristics. When population validity issues are not addressed, researchers cannot generalize findings to other populations of students, and it becomes unclear what intervention strategies work, especially with English language learner student populations. However, 25 studies did specifically recognize and address the needs of English language learners, indicating more researchers are taking into consideration the diverse needs of other struggling student populations.
Synthesis of amino-terminated hyperbranched polymers and their application in microfiber synthetic leather base dyeing
Authors: Ren Longfang , Zhao Guohui , Qiang Taotao , Wang Xuechuan , Wang Na
Published: November 2012

In the current study, amino-terminated hyperbranched polymers (NH2-HBP) were synthesized by Michael addition reaction in which N, N’-methylene bisacrylamide (MBA) and diethylene triamine (DETA) were used as raw materials, and water was used as a solvent. Reaction temperature, raw material ratio, and reaction time were optimized via single-factor experiments in which the production rate and primary amino content were used as indexes. The results showed that the mol ratio of MBA to DETA was 1:1.1, the temperature was 70°C, and reaction time was 24 h. Under this condition, the primary amino content of NH2-HBP was 2.83 mmol/g, and the yield was 91.16%. The NH2-HBP structure was characterized by Fourier transform infrared spectroscopy and nuclear magnetic resonance. Moreover, the relative molecular mass distribution of NH2-HBP was also determined by gel permeation chromatography. As an active substance, NH2-HBP was grafted onto the polyamide microfiber synthetic leather used in clothes, and organic phosphine was used as a cross-linking agent. The change in dye uptake, surface chroma, and resistance to dry-rub and wet-rub fastness properties was discussed. When the NH2-HBP dosage was 5.5%, the dye uptake improved from 56.89% to 94.85% (an increase of almost 61%). The surface chroma also deepened, the dry-rub fastness improved from 3.0 to 4.5, and the wet-rub fastness improved from 2.5 to 3.5.
Developing and Assessing Intercoder Reliability in Studies of Group Interaction
Authors: Compton D’Lane , Love Tony P. , Sell Jane
Published: November 2012

Although group interaction is a rich source of data, it offers many challenges for analysis. We discuss how pretesting can solve many coding and reliability issues before the actual data collection and analysis. We also consider how coding schemes can be developed, how coders can be trained, and how coder reliability can be ascertained. We examine the properties of different estimates of intercoder reliability and detail how these relate to decisions about the data.