bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating MicroRNAs as Novel Biomarkers for Platelet Activation
Authors: Willeit Peter , Zampetaki Anna , Dudek Katarzyna , Kaudewitz Dorothee , King Alice , Kirkby Nicholas S. , Crosby-Nwaobi Roxanne , Prokopi Marianna , Drozdov Ignat , Langley Sarah R. , Sivaprasad Sobha , Markus Hugh S. , Mitchell Jane A. , Warner Timothy D. , Kiechl Stefan , Mayr Manuel
Published: January 2013

Rationale:

MicroRNA (miRNA) biomarkers are attracting considerable interest. Effects of medication, however, have not been investigated thus far.

Objective:

To analyze changes in plasma miRNAs in response to antiplatelet therapy.

Methods and Results:

Profiling for 377 miRNAs was performed in platelets, platelet microparticles, platelet-rich plasma, platelet-poor plasma, and serum. Platelet-rich plasma showed markedly higher levels of miRNAs than serum and platelet-poor plasma. Few abundant platelet miRNAs, such as miR-24, miR-197, miR-191, and miR-223, were also increased in serum compared with platelet-poor plasma. In contrast, antiplatelet therapy significantly reduced miRNA levels. Using custom-made quantitative real-time polymerase chain reaction plates, 92 miRNAs were assessed in a dose-escalation study in healthy volunteers at 4 different time points: at baseline without therapy, at 1 week with 10 mg prasugrel, at 2 weeks with 10 mg prasugrel plus 75 mg aspirin, and at 3 weeks with 10 mg prasugrel plus 300 mg aspirin. Findings in healthy volunteers were confirmed by individual TaqMan quantitative real-time polymerase chain reaction assays (n=9). Validation was performed in an independent cohort of patients with symptomatic atherosclerosis (n=33), who received low-dose aspirin at baseline. Plasma levels of platelet miRNAs, such as miR-223, miR-191, and others, that is, miR-126 and miR-150, decreased on further platelet inhibition.

Conclusions:

Our study demonstrated a substantial platelet contribution to the circulating miRNA pool and identified miRNAs responsive to antiplatelet therapy. It also highlights that antiplatelet therapy and preparation of blood samples could be confounding factors in case-control studies relating plasma miRNAs to cardiovascular disease.
Blood Pressure and Autonomic Responses to Electrical Stimulation of the Renal Arterial Nerves Before and After Ablation of the Renal Artery
Authors: Chinushi Masaomi , Izumi Daisuke , Iijima Kenichi , Suzuki Katsuya , Furushima Hiroshi , Saitoh Osamu , Furuta Yui , Aizawa Yoshifusa , Iwafuchi Mitsuya
Published: January 2013

Radiofrequency (RF) catheter ablation of the renal artery is therapeutic in patients with drug-refractory essential hypertension. This study was designed to examine the role of the renal autonomic nerves and of RF application from inside the renal artery in the regulation of blood pressure (BP). An open irrigation catheter was inserted into either the left or right renal artery in 8 dogs. RF current (17±2 watts) was delivered to one renal artery. Electrical autonomic nerve stimulation was applied to each renal artery before and after RF ablation. BP, heart rate, indices of heart rate variability, and serum catecholamines were analyzed. Before RF ablation, electrical autonomic nerve stimulation of either renal artery increased BP from 150±16/92±15 to 173±21/105±16 mm Hg. After RF ablation, BP increased similarly when the nonablated renal artery was electrically stimulated, although the rise in BP was attenuated when the ablated renal artery was stimulated. Serum catecholamines and sympathetic nerve indices of heart rate variability increased when electrical autonomic nerve stimulation was applied before RF ablation and to the nonablated renal artery after RF ablation, although it changed minimally when the ablated renal artery was stimulated, suggesting interconnectivity between afferent renal nerve stimulation and systemic sympathetic activity. Renal artery angiogram showed no apparent injury after RF ablation. In conclusion, electrical stimulation of the renal arterial autonomic nerves increases BP via an increase in central sympathetic nervous activity. This response might be used to determine the target ablation site and end point of renal artery RF ablation.
Nitric Oxide and Regulation of Heart Rate in Patients With Postural Tachycardia Syndrome and Healthy Subjects
Authors: Gamboa Alfredo , Okamoto Luis E. , Raj Satish R. , Diedrich André , Shibao Cyndya A. , Robertson David , Biaggioni Italo
Published: January 2013

The objective is to study the role of nitric oxide (NO) on cardiovascular regulation in healthy subjects and postural tachycardia syndrome (POTS) patients. Reduced neuronal NO function, which could contribute to a hyperadrenergic state, and increased NO-induced vasodilation, which could contribute to orthostatic intolerance, have been reported in POTS. In protocol 1, 13 healthy volunteers (33±3 years) underwent autonomic blockade with trimethaphan and were administered equipressor doses of Nω-monomethyl-L-arginine (L-NMMA, a NO synthase inhibitor) and phenylephrine to determine the direct chronotropic effects of NO (independent of baroreflex modulation). In protocol 2, we compared the effects of L-NMMA in 9 POTS patients (31±3 years) and 14 healthy (32±2 years) volunteers, during autonomic blockade. During autonomic blockade, L-NMMA and phenylephrine produced similar increases in systolic blood pressure (27±2 versus 27±3 mm Hg). Phenylephrine produced only minimal heart rate changes, whereas L-NMMA produced a modest, but significant, bradycardia (–0.8±0.4 versus –4.8±1.2 bpm;
P
=0.011). There were no differences between POTS and healthy volunteers in the systolic blood pressure increase (22±2 and 28±5 mm Hg) or heart rate decrease (–6±2 and –4±1 bpm for POTS and controls, respectively) produced by L-NMMA. In the absence of baroreflex buffering, inhibition of endogenous NO synthesis results in a significant bradycardia, reflecting direct tonic modulation of heart rate by NO in healthy individuals. We found no evidence of a primary alteration in NO function in POTS. If NO dysfunction plays a role in POTS, it is through its interaction with the autonomic nervous system.
Divisible Transition Systems and Multiplanar Dependency Parsing
Authors: Gómez-Rodríguez Carlos , Nivre Joakim
Published: January 2013

Transition-based parsing is a widely used approach for dependency parsing that combines high efficiency with expressive feature models. Many different transition systems have been proposed, often formalized in slightly different frameworks. In this article, we show that a large number of the known systems for projective dependency parsing can be viewed as variants of the same stack-based system with a small set of elementary transitions that can be composed into complex transitions and restricted in different ways. We call these systems divisible transition systems and prove a number of theoretical results about their expressivity and complexity. In particular, we characterize an important subclass called efficient divisible transition systems that parse planar dependency graphs in linear time. We go on to show, first, how this system can be restricted to capture exactly the set of planar dependency trees and, secondly, how the system can be generalized to k-planar trees by making use of multiple stacks. Using the first known efficient test for k-planarity, we investigate the coverage of k-planar trees in available dependency treebanks and find a very good fit for 2-planar trees. We end with an experimental evaluation showing that our 2-planar parser gives significant improvements in parsing accuracy over the corresponding 1-planar and projective parsers for data sets with non-projective dependency trees and performs on a par with the widely used arc-eager pseudo-projective parser.
Early Visual Responses Predict Conscious Face Perception within and between Subjects during Binocular Rivalry
Authors: Sandberg Kristian , Bahrami Bahador , Kanai Ryota , Barnes Gareth Robert , Overgaard Morten , Rees Geraint
Published: January 2013

Previous studies indicate that conscious face perception may be related to neural activity in a large time window around 170–800 msec after stimulus presentation, yet in the majority of these studies changes in conscious experience are confounded with changes in physical stimulation. Using multivariate classification on MEG data recorded when participants reported changes in conscious perception evoked by binocular rivalry between a face and a grating, we showed that only MEG signals in the 120–320 msec time range, peaking at the M170 around 180 msec and the P2m at around 260 msec, reliably predicted conscious experience. Conscious perception could not only be decoded significantly better than chance from the sensors that showed the largest average difference, as previous studies suggest, but also from patterns of activity across groups of occipital sensors that individually were unable to predict perception better than chance. In addition, source space analyses showed that sources in the early and late visual system predicted conscious perception more accurately than frontal and parietal sites, although conscious perception could also be decoded there. Finally, the patterns of neural activity associated with conscious face perception generalized from one participant to another around the times of maximum prediction accuracy. Our work thus demonstrates that the neural correlates of particular conscious contents (here, faces) are highly consistent in time and space within individuals and that these correlates are shared to some extent between individuals.
Jesus and the minjung revisited: The Legacy of Ahn Byung-Mu (1922-1996)
Authors: Küster Volker
Published: January 2013

Ahn Byung-Mu was not only one of the leading theological thinkers of 20th century Korea, a mediator between Western, especially German theological tradition and Korean Christianity, but also a persistent regime critique under South Korea's development dictatorship of the 1970s and 80s. Originally a New Testament scholar he also became one of the founding fathers of minjung theology by giving this political theology in the Korean context a biblical foundation. In his studies on the Gospel of Mark, Ahn advocates the thesis that German historical-critical exegesis viewed the Markan ochlos from the perspective of form criticism as a dramatic element similar to the “antique choir”, thereby failing to acknowledge its social and theological significance. In contrast, he emphasizes Jesus' unconditional commitment to the ochlos, which is displayed in the Gospel of Mark. The Galilean ochlos, an amorphous, and in its membership varying group of people from the Galilean lower class, is the addressee of Jesus' mission. The article reconstructs Ahn Byung Mu's theological way of thinking and tackles the question how his legacy can be re-contextualized.
An integrative, synergistic reading of Romans 1-3
Authors: Spitaler Peter
Published: January 2013

The purpose of this article is to analyze a theme cluster that meanders through the narrative fabric of Romans 1-3—the justice of God and the justice and injustice of people. The article (1) describes the literary scope and theological content of the theme cluster statements; (2) examines the plausibility of a relationship between humans and God; (3) critiques traditional interpretations of Paul's diverse descriptions of conduct; and (4) explains the intricacies of the theme cluster from the perspective of “synergy.” As a contextual reading strategy, synergy explores the complementary nature of the theme cluster. The analysis leads to the conclusion: a pessimistic anthropology attributed to Paul overshadows his statements about human and divine justice.
“I Can Just Be Me”
Authors: Thirsk Lorraine M. , Moules Nancy J.
Published: January 2013

Nurses have a key role to play in therapeutic interventions for bereaved and grieving families. In this article, hermeneutic inquiry is used to uncover what families found helpful or useful with respect to therapeutic conversations with advanced practice registered nurses. The findings show that nursing expertise is important in family nursing practice. Expertise in the relationship allowed the family to find healing and hope by addressing core constraining beliefs. Clinical judgment, or sense, was significant in guiding the therapeutic conversation. Lastly, how problems are framed and how families are positioned have implications for outcomes and therapeutic change.
NeuroDNet - an open source platform for constructing and analyzing neurodegenerative disease networks
Authors: Vasaikar Suhas V , Padhi Aditya K , Jayaram Bhyravabhotla , Gomes James
Published: January 2013

Background

Genetic networks control cellular functions. Aberrations in normal cellular function are caused by mutations in genes that disrupt the fine tuning of genetic networks and cause disease or disorder. However, the large number of signalling molecules, genes and proteins that constitute such networks, and the consequent complexity of interactions, has restrained progress in research elucidating disease mechanisms. Hence, carrying out a systematic analysis of how diseases alter the character of these networks is important. We illustrate this through our work on neurodegenerative disease networks. We created a database, NeuroDNet, which brings together relevant information about signalling molecules, genes and proteins, and their interactions, for constructing neurodegenerative disease networks.

Description

NeuroDNet is a database with interactive tools that enables the creation of interaction networks for twelve neurodegenerative diseases under one portal for interrogation and analyses. It is the first of its kind, which enables the construction and analysis of neurodegenerative diseases through protein interaction networks, regulatory networks and Boolean networks. The database has a three-tier architecture - foundation, function and interface. The foundation tier contains the human genome data with 23857 protein-coding genes linked to more than 300 genes reported in clinical studies of neurodegenerative diseases. The database architecture was designed to retrieve neurodegenerative disease information seamlessly through the interface tier using specific functional information. Features of this database enable users to extract, analyze and display information related to a disease in many different ways.

Conclusions

The application of NeuroDNet was illustrated using three case studies. Through these case studies, the construction and analyses of a PPI network for angiogenin protein in amyotrophic lateral sclerosis, a signal-gene-protein interaction network for presenilin protein in Alzheimer's disease and a Boolean network for a mammalian cell cycle was demonstrated. NeuroDNet is accessible at http://bioschool.iitd.ac.in/NeuroDNet/.
Quantitative low mechanical index contrast-enhanced endoscopic ultrasound for the differential diagnosis of chronic pseudotumoral pancreatitis and pancreatic cancer
Authors: Gheonea Dan Ionuţ , Streba Costin Teodor , Ciurea Tudorel , Săftoiu Adrian
Published: January 2013

Background

Second-generation intravenous blood-pool ultrasound contrast agents are increasingly used in endoscopic ultrasound (EUS) for characterization of microvascularization, differential diagnosis of benign and malignant focal lesions, as well as improved staging and guidance of therapeutic procedures.

Methods

The aim of our study was to prospectively compare the vascularisation patterns in chronic pseudotumoral pancreatitis and pancreatic cancer using quantitative low mechanical index (MI) contrast-enhanced EUS. We included 51 patients with chronic pseudotumoral pancreatitis (n = 19) and pancreatic cancer (n = 32). Perfusion imaging started with a bolus injection of Sonovue (2.4 ml), followed by analysis in the early arterial (wash-in) and late venous (wash-out) phase. Perfusion analysis was performed by post-processing of the raw data (time intensity curve [TIC] analysis). TIC analysis was performed inside the tumor and the pancreatic parenchyma, with depiction of the dynamic vascular pattern generated by specific software. Statistical analysis was performed on raw data extracted from the TIC analysis. Final diagnosis was based on a combination of EUS-FNA, surgery and follow-up of minimum 6 months in negative cases.

Results

The sensitivity and specificity of low MI contrast enhanced EUS using TIC were sensitivity and specificity of low MI contrast enhanced EUS using TIC analysis were 93.75% (95% CI = 77.77 - 98.91%) and 89.47% (95% CI = 65.46 - 98.15%), respectively. Pseudotumoral chronic pancreatitis showed in the majority of cases a hypervascular appearance in the early arterial phase of contrast-enhancement, with a dynamic enhancement pattern similar with the rest of the parenchyma. Statistical analysis of the resulting series of individual intensities revealed no statistically relevant differences (p = .78). Pancreatic adenocarcinoma was usually a hypovascular lesion, showing low contrast-enhancement during the early arterial and also during the late venous phase of contrast-enhancement, also lower than the normal surrounding parenchyma. We found statistically significant differences in values during TIC analysis (p < .001).

Conclusions

Low MI contrast enhanced EUS technique is expected to improve the differential diagnosis of focal pancreatic lesions. However, further multicentric randomized studies will confirm the exact role of the technique and its place in imaging assessment of focal pancreatic lesions.
Genetic manipulation of longevity-related genes as a tool to regulate yeast life span and metabolite production during winemaking
Authors: Orozco Helena , Matallana Emilia , Aranda Agustín
Published: January 2013

Background

Yeast viability and vitality are essential for different industrial processes where the yeast Saccharomyces cerevisiae is used as a biotechnological tool. Therefore, the decline of yeast biological functions during aging may compromise their successful biotechnological use. Life span is controlled by a variety of molecular mechanisms, many of which are connected to stress tolerance and genomic stability, although the metabolic status of a cell has proven a main factor affecting its longevity. Acetic acid and ethanol accumulation shorten chronological life span (CLS), while glycerol extends it.

Results

Different age-related gene classes have been modified by deletion or overexpression to test their role in longevity and metabolism. Overexpression of histone deacetylase SIR2 extends CLS and reduces acetate production, while overexpression of SIR2 homolog HST3 shortens CLS, increases the ethanol level, and reduces acetic acid production. HST3 overexpression also enhances ethanol tolerance. Increasing tolerance to oxidative stress by superoxide dismutase SOD2 overexpression has only a moderate positive effect on CLS. CLS during grape juice fermentation has also been studied for mutants on several mRNA binding proteins that are regulators of gene expression at the posttranscriptional level; we found that NGR1 and UTH4 deletions decrease CLS, while PUF3 and PUB1 deletions increase it. Besides, the pub1 Δ mutation increases glycerol production and blocks stress granule formation during grape juice fermentation. Surprisingly, factors relating to apoptosis, such as caspase Yca1 or apoptosis-inducing factor Aif1, play a positive role in yeast longevity during winemaking as their deletions shorten CLS.

Conclusions

Manipulation of regulators of gene expression at both transcriptional (i.e., sirtuins) and posttranscriptional (i.e., mRNA binding protein Pub1) levels allows to modulate yeast life span during its biotechnological use. Due to links between aging and metabolism, it also influences the production profile of metabolites of industrial relevance.
Ascaris co-infection does not alter malaria-induced anaemia in a cohort of Nigerian preschool children
Authors: Abanyie Francisca A , McCracken Courtney , Kirwan Patrick , Molloy Síle F , Asaolu Samuel O , Holland Celia V , Gutman Julie , Lamb Tracey J
Published: January 2013

Background

Co-infection with malaria and intestinal parasites such asAscaris lumbricoidesis common. Malaria parasites induce a pro-inflammatory immune response that contributes to the pathogenic sequelae, such as malarial anaemia, that occur in malaria infection.Ascarisis known to create an anti-inflammatory immune environment which could, in theory, counteract the anti-malarial inflammatory immune response, minimizing the severity of malarial anaemia. This study examined whetherAscarisco-infection can minimize the severity of malarial anaemia.

Methods

Data from a randomized controlled trial on the effect of antihelminthic treatment in Nigerian preschool-aged (6–59 months) children conducted in 2006–2007 were analysed to examine the effect of malaria andAscarisco-infection on anaemia severity. Children were enrolled and tested for malaria, helminths and anaemia at baseline, four, and eight months. Six hundred and ninety subjects were analysed in this study. Generalized linear mixed models were used to assess the relationship between infection status andAscarisandPlasmodiumparasite intensity on severity of anaemia, defined as a haemoglobin less than 11 g/dL.

Results

Malaria prevalence ranged from 35-78% over the course of this study. Of the malaria-infected children, 55% were co-infected withAscarisat baseline, 60% were co-infected four months later and 48% were co-infected eight months later, underlining the persistent prevalence of malaria-nematode co-infections in this population. Over the course of the study the percentage of anaemic subjects in the population ranged between 84% at baseline and 77% at the eight-month time point. The odds of being anaemic were four to five times higher in children infected with malaria compared to those without malaria.Ascarisinfection alone did not increase the odds of being anaemic, indicating that malaria was the main cause of anaemia in this population. There was no significant difference in the severity of anaemia between children singly infected with malaria and co-infected with malaria andAscaris.

Conclusion

In this cohort of Nigerian preschool children, malaria infection was the major contributor to anaemia status.Ascarisco-infection neither exacerbated nor ameliorated the severity of malarial anaemia.
Proteomic analysis of ERK1/2-mediated human sickle red blood cell membrane protein phosphorylation
Authors: Soderblom Erik J , Thompson J Will , Schwartz Evan A , Chiou Edward , Dubois Laura G , Moseley M Arthur , Zennadi Rahima
Published: January 2013

Background

In sickle cell disease (SCD), the mitogen-activated protein kinase (MAPK) ERK1/2 is constitutively active and can be inducible by agonist-stimulation only in sickle but not in normal human red blood cells (RBCs). ERK1/2 is involved in activation of ICAM-4-mediated sickle RBC adhesion to the endothelium. However, other effects of the ERK1/2 activation in sickle RBCs leading to the complex SCD pathophysiology, such as alteration of RBC hemorheology are unknown.

Results

To further characterize global ERK1/2-induced changes in membrane protein phosphorylation within human RBCs, a label-free quantitative phosphoproteomic analysis was applied to sickle and normal RBC membrane ghosts pre-treated with U0126, a specific inhibitor of MEK1/2, the upstream kinase of ERK1/2, in the presence or absence of recombinant active ERK2. Across eight unique treatment groups, 375 phosphopeptides from 155 phosphoproteins were quantified with an average technical coefficient of variation in peak intensity of 19.8%. Sickle RBC treatment with U0126 decreased thirty-six phosphopeptides from twenty-one phosphoproteins involved in regulation of not only RBC shape, flexibility, cell morphology maintenance and adhesion, but also glucose and glutamate transport, cAMP production, degradation of misfolded proteins and receptor ubiquitination. Glycophorin A was the most affected protein in sickle RBCs by this ERK1/2 pathway, which contained 12 unique phosphorylated peptides, suggesting that in addition to its effect on sickle RBC adhesion, increased glycophorin A phosphorylation via the ERK1/2 pathway may also affect glycophorin A interactions with band 3, which could result in decreases in both anion transport by band 3 and band 3 trafficking. The abundance of twelve of the thirty-six phosphopeptides were subsequently increased in normal RBCs co-incubated with recombinant ERK2 and therefore represent specific MEK1/2 phospho-inhibitory targets mediated via ERK2.

Conclusions

These findings expand upon the current model for the involvement of ERK1/2 signaling in RBCs. These findings also identify additional protein targets of this pathway other than the RBC adhesion molecule ICAM-4 and enhance the understanding of the mechanism of small molecule inhibitors of MEK/1/2/ERK1/2, which could be effective in ameliorating RBC hemorheology and adhesion, the hallmarks of SCD.
Pathogenic characteristics of three genotype II porcine reproductive and respiratory syndrome viruses isolated from China
Authors: Shang Youjun , Wang Guangxiang , Yin Shuanghui , Tian Hong , Du Ping , Wu Jinyan , Chen Yan , Yang Shunli , Jin Ye , Zhang Keshan , Lu Zengjun , Liu Xiangtao
Published: January 2013

Background

We examined differences in pathogenicity in pigs from China that had been experimentally infected with porcine reproductive and respiratory syndrome virus (PRRSV).

Methods

We compared pathogenic characteristics of a field isolate (GX-1/2008F), two PRRSV isolates (HN-1/2008, YN-1/2008) propagated in cells, and GX-1/2008F that had been propagated in cells (GX-1/2008). The clinical courses, along with humoral and cell-mediated responses, were monitored for 21 days post-infection (DPI). Animals were sacrificed and tissue samples used for gross pathological, histopathological and ultrastructure examination.

Results

At 2–3 DPI, animals infected with cell-propagated viruses exhibited signs of coughing, anorexia and fever. However their rectal temperature did not exceed 40.5°C. Viremia was detectable as early as 3 DPI in animals infected with HN-1/2008 and YN-1/2008. Animals inoculated with GX-1/2008F displayed clinical signs at 6 DPI; the rectal temperature of two animals in this group exceeded 41.0°C, with viremia first detected at 7 DPI. Seroconversion for all challenged pigs, except those infected with GX-1/2008, was seen as early as 7 DPI. All of these pigs had fully seroconverted by 11 DPI. All animals challenged with GX-1/2008 remained seronegative until the end of the experiment. Innate immunity was inhibited, with levels of IFN-α and IL-1 not significantly different between control and infected animals. The cytokines IFN-γ and IL-6 transiently increased during acute infection. All virus strains caused gross lesions including multifocal interstitial pneumonia and hyperplasia of lymph nodes. Inflammation of the stomach and small intestine was also observed. Lesions in the group infected with GX-1/2008F were more serious than in other groups. Transmission electron microscopy revealed that alveolar macrophages, plasmacytes and lymphocytes had fractured cytomembranes, and hepatocytes had disrupted organelles and swollen mitochondria.

Conclusions

The pathogenicity of the PRRSV field isolate became attenuated when propagated in MARC-145 cells. Tissue tropism of highly pathogenic strains prevailing in China was altered compared with classical PRRSV strains. The observed damage to immune cells and modulation of cytokine production could be mechanisms that PRRSV employs to evade host immune responses.
Effects of acupuncture treatment on depression insomnia: a study protocol of a multicenter randomized controlled trial
Authors: Chen Yuan-Fang , Liu Jian-Hua , Xu Neng-Gui , Liang Zhao-Hui , Xu Zhen-Hua , Xu Shu-Jun , Fu Wen-Bin
Published: January 2013

Background

More than 70% of patients with depression who see their doctors experience insomnia. Insomnia treatment is a very important link for depression treatment. Furthermore, antidepression treatment is also important for depression insomnia. In acupuncture, LU-7 (Lie Que) and KID-6 (Zhao Hai), which are two of the eight confluence points in meridian theory, are used as main points. An embedded needle technique is used, alternately, at two groups of points to consolidate the treatment effect. These two groups of points are BL-15 (Xin Shu) with BL-23 (Shen Shu) and BL-19 (Dan Shu) with N-HN-54 (An Mian). The effectiveness of these optimized acupuncture formulas is well proven in the practice by our senior acupuncturists in Guangdong Provincial Hospital of TCM. This study has been designed to examine whether this set of optimized clinical formulas is able to increase the clinical efficacy of depression insomnia treatment.

Methods/design

In this randomized controlled multicenter trial, all the eligible participants are diagnosed with depression insomnia. All participants are randomly assigned to one of two groups in a ratio of 1:1 and receive either conventional acupuncture treatment or optimized acupuncture treatment. Patients are evaluated using the Pittsburgh Sleep Quality Index(PSQI)and the Hamilton rating scale(HAMD) for depression. The use of antidepression and hypnotics drugs is also considered. Results are obtained at the start of treatment, 1 and 2 months after treatment has begun, and at the end of treatment. The entire duration of the study will be approximately 36 months.

Discussion

A high quality of trial methodologies is utilized in the study, and the results may provide better evidence for the effectiveness of acupuncture as a treatment for depression insomnia. The optimized acupuncture formula has potential benefits in increasing the efficacy of treating depression insomnia.

Trial registration

The trial was registered in Chinese Clinical Trial Register (ChiCR-TRC-00000481) on 12 August 2009.
Radiotherapy in marginal zone lymphoma
Authors: Deinbeck Kristin , Geinitz Hans , Haller Bernhard , Fakhrian Khashayar
Published: January 2013

Purpose

To evaluate the efficacy of radiotherapy (RT) for early-stage nodal and extranodal marginal zone lymphoma (MZL).

Materials and methods

Patients with stage I (n = 22) and stage II (n = 8) MZL, who were treated with RT were reviewed. The primary tumor localisation was in the orbita (n = 12), stomach (n = 8), head and neck other than the orbita (n = 8), breast (n = 1) and one case of marginal zone lymphoma of the skin (n = 1). The median radiotherapy dose was 40 Gy (5 to 45 Gy).

Results

The median follow-up time was 103 months. The 5-year overall survival and event-free survival rates were 85 ± 7% and 71 ± 9%, respectively. There was no infield recurrence. Recurrence occurred outside of the radiation field in six patients. The relapses were treated with salvage RT and had excellent local control (100%) at five years after salvage RT.

Conclusions

Localized extranodal MZL have an excellent prognosis following moderate-dose RT. RT is also an effective salvage therapy in cases of localized recurrence. Further clinical studies should evaluate the optimal dose for MZL.
Revisiting the evolution of mouse LINE-1 in the genomic era
Authors: Sookdeo Akash , Hepp Crystal M , McClure Marcella A , Boissinot Stéphane
Published: January 2013

Background

LINE-1 (L1) is the dominant category of transposable elements in placental mammals. L1 has significantly affected the size and structure of all mammalian genomes and understanding the nature of the interactions between L1 and its mammalian host remains a question of crucial importance in comparative genomics. For this reason, much attention has been dedicated to the evolution of L1. Among the most studied elements is the mouse L1 which has been the subject of a number of studies in the 1980s and 1990s. These seminal studies, performed in the pre-genomic era when only a limited number of L1 sequences were available, have significantly improved our understanding of L1 evolution. Yet, no comprehensive study on the evolution of L1 in mouse has been performed since the completion of this genome sequence.

Results

Using the Genome Parsing Suite we performed the first evolutionary analysis of mouse L1 over the entire length of the element. This analysis indicates that the mouse L1 has recruited novel 5’UTR sequences more frequently than previously thought and that the simultaneous activity of non-homologous promoters seems to be one of the conditions for the co-existence of multiple L1 families or lineages. In addition the exchange of genetic information between L1 families is not limited to the 5’UTR as evidence of inter-family recombination was observed in ORF1, ORF2, and the 3’UTR. In contrast to the human L1, there was little evidence of rapid amino-acid replacement in the coiled-coil of ORF1, although this region is structurally unstable. We propose that the structural instability of the coiled-coil domain might be adaptive and that structural changes in this region are selectively equivalent to the rapid evolution at the amino-acid level reported in the human lineage.

Conclusions

The pattern of evolution of L1 in mouse shows some similarity with human suggesting that the nature of the interactions between L1 and its host might be similar in these two species. Yet, some notable differences, particularly in the evolution of ORF1, suggest that the molecular mechanisms involved in host-L1 interactions might be different in these two species.
Urease inhibitory activities of β-boswellic acid derivatives
Authors: Golbabaei Sanaz , Bazl Roya , Golestanian Sahand , Nabati Farzaneh , Omrany Zinat Bahrampour , Yousefi Behnam , Hajiaghaee Reza , Rezazadeh Shamsali , Amanlou Massoud
Published: January 2013

Background and the purpose of the study

Boswellia carterii have been used in traditional medicine for many years for management different gastrointestinal disorders. In this study, we wish to report urease inhibitory activity of four isolated compound of boswellic acid derivative.

Methods

4 pentacyclic triterpenoid acids were isolated from Boswellia carterii and identified by NMR and Mass spectroscopic analysis (compounds 1, 3-O-acetyl-9,11-dehydro-β-boswellic acid; 2, 3-O-acetyl-11-hydroxy-β-boswellic acid; 3. 3-O- acetyl-11-keto-β-boswellic acid and 4, 11-keto-β-boswellic acid. Their inhibitory activity on Jack bean urease were evaluated. Docking and pharmacophore analysis using AutoDock 4.2 and Ligandscout 3.03 programs were also performed to explain possible mechanism of interaction between isolated compounds and urease enzyme.

Results

It was found that compound 1 has the strongest inhibitory activity against Jack bean urease (IC50 = 6.27 ± 0.03 μM), compared with thiourea as a standard inhibitor (IC50 = 21.1 ± 0.3 μM).

Conclusion

The inhibition potency is probably due to the formation of appropriate hydrogen bonds and hydrophobic interactions between the investigated compounds and urease enzyme active site and confirms its traditional usage.
Mental health tribunals in England and Wales: a representative's guide
Authors: Jones Chris , Nimmagadda Srikanth , Veitch Paul
Published: January 2013

Consultant psychiatrists are familiar with mental health tribunals, at which they appear as key witnesses giving both factual evidence and expert opinion. They also commonly act as the representative of the ‘responsible authority’. The implications of this in terms of roles and responsibilities, and in terms of training and continuing professional development, have received little attention. Psychiatrists should not accept a representative role unless they are sure that they have the necessary competencies and resources – competencies that are alien to most clinicians and resources that are not available in many services. This article outlines those requirements so that psychiatrists can make better-informed decisions about whether or not to undertake the role and provides practical guidance for those who choose to do so.
Clinical staging in severe mental disorder: evidence from neurocognition and neuroimaging
Authors: Lin Ashleigh , Reniers Renate L. E. P. , Wood Stephen J.
Published: January 2013

A new approach to understanding severe mental illnesses such as schizophrenia and affective disorders is to adopt a clinical staging model. Such a model defines the extent of the illness such that earlier and milder phenomena are distinguished from later, more impairing features. Part of the appeal of such a model is that it should have cross-diagnostic applications, but to date there has been no attempt to examine imaging or neurocognrtive evidence for staging in this way. We review these two domains of study with particular focus on major depression and bipolar affective disorder. Although there is some support for the staging model in affective disorders, conclusions are limited by the large variability in the clinical samples studied, especially with regard to the presence of psychotic symptoms. We suggest that future research needs to take a transdiagnostic and longitudinal approach.
Declining Second Primary Ovarian Cancer After First Primary Breast Cancer
Authors: Schonfeld Sara J. , de Gonzalez Amy Berrington , Visvanathan Kala , Pfeiffer Ruth M. , Anderson William F.
Published: January 2013

Purpose

Although ovarian cancer incidence rates have declined in the United States, less is known of ovarian cancer trends among survivors of breast cancer. Therefore, we examined second primary ovarian cancers after first primary breast cancer.

Methods

Data were obtained from the Surveillance, Epidemiology, and End Results program (1973 to 2008). Standardized incidence ratios (SIRs) were calculated as the observed numbers of ovarian cancers among survivors of breast cancer compared with the expected numbers in the general population. Absolute rates were measured as the incidence rates for second primary ovarian cancer by year of diagnosis of the first primary breast cancer adjusted for age of breast cancer diagnosis and years since diagnosis.

Results

SIRs for second primary ovarian cancer were elevated over the entire study period (SIR, 1.24; 95% CI, 1.2 to 1.3), whereas the absolute rates declined with an estimated annual percentage change near 1% (−1.34% to −0.09% per year). Secular trends for second ovarian cancers were similar after estrogen receptor (ER) –positive and ER-negative breast cancers, whereas the age-specific patterns varied significantly by ER expression (P for interaction < .001). The largest SIR was among women age less than 50 years with ER-negative breast cancer (SIR, 4.35; 95% CI, 3.5 to 5.4).

Conclusion

Persistently elevated SIRs along with decreasing absolute rates over the entire study period suggest that ovarian cancers in both the general population and survivors of breast cancer are declining in parallel, possibly because of common risk factor exposures. Analytic studies are needed to further assess the parallel overall trends and the age-specific interaction by ER expression.
High Familial Risk in Nodular Lymphocyte-Predominant Hodgkin Lymphoma
Authors: Saarinen Silva , Pukkala Eero , Vahteristo Pia , Mäkinen Markus J. , Franssila Kaarle , Aaltonen Lauri A.
Published: January 2013

Purpose

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is one of the two established Hodgkin lymphoma (HL) subtypes. The risk factors of NLPHL are largely unknown. In general, genetic factors are known to have a modest effect on the risk of HL; however, familial risk in NLPHL has not been previously examined. We conducted a population-based study by using the Finnish registries and evaluated the familial risk in NLPHL.

Patients and Methods

We launched a population-based search to identify patients with NLPHL and their relatives by examining the records of the Finnish Cancer Registry, established in 1953, and the official Finnish population registries. We collected a data set of 692 patients with NLPHL, identified their 4,280 first-degree relatives, and calculated the registry-based standardized incidence ratios (SIRs) for different cancers in the first-degree relatives. In addition, the primary tumor biopsies of HL-affected relatives were collected when possible, the HL diagnoses were re-reviewed by a hematopathologist, and the SIR for NLPHL was calculated on the basis of confirmed NLPHL diagnoses.

Results

On the basis of confirmed NLPHL diagnoses, the SIR for NLPHL was 19 (95% CI, 8.8 to 36) in the first-degree relatives. The risk was most prominent in female relatives of young patients. The registry-based SIR for classical HL was 5.3 (95% CI, 3.0 to 8.8), and for non-Hodgkin lymphoma, it was 1.9 (95% CI, 1.3 to 2.6).

Conclusion

Our results implicate an unexpectedly high familial component in the development of NLPHL. Research is warranted to identify the putative genetic and environmental factors underlying this finding and to develop strategies for better management of patients with NLPHL and their relatives.
Parathyroid Hormone-Related Protein Is a Mitogenic and a Survival Factor of Mesangial Cells from Male Mice: Role of Intracrine and Paracrine Pathways
Authors: Hochane Mazène , Raison Denis , Coquard Catherine , Imhoff Olivier , Massfelder Thierry , Moulin Bruno , Helwig Jean-Jacques , Barthelmebs Mariette
Published: January 2013

Glomerulonephritis is characterized by the proliferation and apoptosis of mesangial cells (MC). The parathyroid-hormone related protein (PTHrP) is a locally active cytokine that affects these phenomena in many cell types, through either paracrine or intracrine pathways. The aim of this study was to evaluate the effect of both PTHrP pathways on MC proliferation and apoptosis. In vitro studies were based on MC from male transgenic mice allowing PTHrP-gene excision by a CreLoxP system. MC were also transfected with different PTHrP constructs: wild type PTHrP, PTHrP devoid of its signal peptide, or of its nuclear localization sequence. The results showed that PTHrP deletion in MC reduced their proliferation even in the presence of serum and increased their apoptosis when serum-deprived. PTH1R activation by PTHrP(1–36) or PTH(1–34) had no effect on proliferation but improved MC survival. Transfection of MC with PTHrP devoid of its signal peptide significantly increased their proliferation and minimally reduced their apoptosis. Overexpression of PTHrP devoid of its nuclear localization sequence protected cells from apoptosis without changing their proliferation. Wild type PTHrP transfection conferred both mitogenic and survival effects, which seem independent of midregion and C-terminal PTHrP fragments. PTHrP-induced MC proliferation was associated with p27Kip1 down-regulation and c-Myc/E2F1 up-regulation. PTHrP increased MC survival through the activation of cAMP/protein kinase A and PI3-K/Akt pathways. These results reveal that PTHrP is a cytokine of multiple roles in MC, acting as a mitogenic factor only through an intracrine pathway, and reducing apoptosis mainly through the paracrine pathway. Thus, PTHrP appears as a probable actor in MC injuries.
The Lumpenproletariat, the Subaltern, the Mental Asylum
Authors: Khanna Ranjana
Published: January 2013

Khanna engages the notion of the lumpenproletariat in Frantz Fanon, tracing the concept through Karl Marx and Friedrich Engels, its transformation through Fanon, and its commonality with and distinction from notions of the subaltern. She draws in particular on the material in The Wretched of the Earth, on mental asylums, and on Fanon’s work as a psychiatrist to think of the radical form of subjectivity announced in mental life, an engagement with an idea of rogues, and a politics that emerges less from a sense of the moral or of right than of desubjectivation. As she puts Fanon’s work in the context of other texts on the mental asylum from 1961 by Michel Foucault, Erving Goffman, and R. D. Laing, she produces a feminist reading of the mental asylum as a site in which one can understand the relationship between madness and violence, and as at once refuge and carceral space.
Hedging Against the Government: A Solution to the Home Asset Bias Puzzle
Authors: Berriel Tiago C , Bhattarai Saroj
Published: January 2013

We explain why international nominal bonds and equity portfolios are biased domestically. In our model, holding domestic government nominal debt provides a hedge against shocks to bond returns and the impact on taxes they induce. For this result, only two features are essential: nominal risk and taxes only on domestic agents. A third feature explains domestically biased equity holdings: government spending falls on domestic goods. Then, an increase in government spending raises the returns on domestic equity, providing a hedge against the subsequent increase in taxes. A calibrated version of the model predicts asset holdings that quantitatively match the data. (JEL F30, G11, G15, H61, H63)
Identifying the Effects of Bank Failures from a Natural Experiment in Mississippi during the Great Depression
Authors: Ziebarth Nicolas L
Published: January 2013

I examine the causal effect of bank failures during the Great Depression using the quasi-experimental setup of Richardson and Troost (2009). The experiment is based on Mississippi being divided into two Federal Reserve districts, which followed different policies for liquidity provision. This translated into variation in bank failures across the state. Employing a plant-level sample from the Census of Manufactures, I find that banking failures had a negative effect on revenue stemming from a fall in physical output. I find no effect on employment at the plant-level and a large decline at the county-level. (JEL E32, E44, G21, G33, N12, N22, N92)
Investigation into High-Temperature Stability of Asphalt Pavement
Authors: Huang Xiaoming , Xu Tao , Zhao Yongli , Li Zhidong
Published: January 2013

To identify potential causes of the unstability problems of asphalt pavement at high temperature, effects of reinforced fiber, asphalt content, and temperature on the stability were analyzed using the wheel tracking test, the triaxial repeated load test (TRT), and partial triaxial test (PTT). The results indicated that Sup19 shows a better rutting resistance and lower permanent deformation than that of AC20, and the polyester fiber has significantly improved the rutting resistance of asphalt mixtures. The asphalt content affects greatly the mixture deformation. PTT method is more sensitive to asphalt content change. High-temperature facilitates to reduce the viscosity of asphalt binder and internal friction between the aggregate particles, resulting in permanent deformation. And most permanent deformation occurs at the first loading cycles because of densification followed by a slight increase in permanent deformation owing to plastic flow. It is concluded that the asphalt content and mixture compaction should be controlled strictly during construction, and fiber can improve the resistance to rutting in pavement, and PTT method can better understand dynamic properties of asphalt mixtures.
Characterization of Asphalt Mixture Homogeneity Based on X-ray Computed Tomography
Authors: Hu Chichun , Youtcheff Jack , Wang Duanyi , Zhang Xiaoning , Kutay Emin , Thyagarajan Senthilmurugan
Published: January 2013

The mechanical performance and life span of asphalt pavement depend largely on the homogeneity of the asphalt mixture. Inhomogeneity of asphalt mixtures is due to the non-uniform segregation of air voids and aggregates in mixtures. In order to evaluate the homogeneity of an asphalt mixture during lab compaction, computed tomography (CT) images of the specimen were obtained based on x-ray CT. The image was virtually cut into slices of various sizes, and the vertical air void distributions and aggregate gradations were quantified. Research results reveal that the air void content in the middle part of the specimen was lower than those on both ends. Also, the homogeneity was better under high compaction levels. The results from aggregate gradations were in good agreement with air void distribution calculations. Therefore, it is feasible to characterize an asphalt mixture’s homogeneity based on the air void distributions and aggregate gradations as determined via x-ray CT.