bluuebunny/crossref_metadata_2025 huggingface dataset:
Book Review: The Plot Against the NHS
Authors: Nundy Madhurima
Published: July 2013

Colin Leys and Stewart Player, The Plot Against the NHS, Wales, Merlin Press, 2011.

(The Indian print of the book has been brought out by the Public Health Resource Society and is available at a nominal price of ₹120)
Book Review: Right to Work and Rural India—Working of the Mahatma Gandhi National Rural Employment Guarantee Scheme
Authors: Saha Partha
Published: July 2013

Ashok K. Pankaj, Right to Work and Rural India—Working of the Mahatma Gandhi National Rural Employment Guarantee Scheme, New Delhi, SAGE, 2012.
Clinical Practice Guideline: Tympanostomy Tubes in Children—Executive Summary
Authors: Rosenfeld Richard M. , Schwartz Seth R. , Pynnonen Melissa A. , Tunkel David E. , Hussey Heather M. , Fichera Jeffrey S. , Grimes Alison M. , Hackell Jesse M. , Harrison Melody F. , Haskell Helen , Haynes David S. , Kim Tae W. , Lafreniere Denis C. , LeBlanc Katie , Mackey Wendy L. , Netterville James L. , Pipan Mary E. , Raol Nikhila P. , Schellhase Kenneth G.
Published: July 2013

The American Academy of Otolaryngology—Head and Neck Surgery Foundation (AAO‐HNSF) has published a supplement to this issue featuring the new Clinical Practice Guideline: Tympanostomy Tubes in Children. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 12 recommendations developed address patient selection, surgical indications for and management of tympanostomy tubes in children. The development group broadly discussed indications for tube placement, perioperative management, care of children with indwelling tubes, and outcomes of tympanostomy tube surgery. Given the lack of current published guidance on surgical indications, the group focused on situations in which tube insertion would be optional, recommended, or not recommended. Additional emphasis was placed on opportunities for quality improvement, particularly regarding shared decision making and care of children with existing tubes.
Variable risk control via stochastic optimization
Authors: Kuindersma Scott R , Grupen Roderic A , Barto Andrew G
Published: July 2013

We present new global and local policy search algorithms suitable for problems with policy-dependent cost variance (or risk), a property present in many robot control tasks. These algorithms exploit new techniques in non-parametric heteroscedastic regression to directly model the policy-dependent distribution of cost. For local search, the learned cost model can be used as a critic for performing risk-sensitive gradient descent. Alternatively, decision-theoretic criteria can be applied to globally select policies to balance exploration and exploitation in a principled way, or to perform greedy minimization with respect to various risk-sensitive criteria. This separation of learning and policy selection permits variable risk control, where risk-sensitivity can be flexibly adjusted and appropriate policies can be selected at runtime without relearning. We describe experiments in dynamic stabilization and manipulation with a mobile manipulator that demonstrate learning of flexible, risk-sensitive policies in very few trials.
Inference on networks of mixtures for robust robot mapping
Authors: Olson Edwin , Agarwal Pratik
Published: July 2013

The central challenge in robotic mapping is obtaining reliable data associations (or “loop closures”): state-of-the-art inference algorithms can fail catastrophically if even one erroneous loop closure is incorporated into the map. Consequently, much work has been done to push error rates closer to zero. However, a long-lived or multi-robot system will still encounter errors, leading to system failure. We propose a fundamentally different approach: allow richer error models that allow the probability of a failure to be explicitly modeled. In other words, rather than characterizing loop closures as being “right” or “wrong”, we propose characterizing the error of those loop closures in a more expressive manner that can account for their non-Gaussian behavior. Our approach leads to an fully integrated Bayesian framework for dealing with error-prone data. Unlike earlier multiple-hypothesis approaches, our approach avoids exponential memory complexity and is fast enough for real-time performance. We show that the proposed method not only allows loop closing errors to be automatically identified, but also that in extreme cases, the “front-end” loop-validation systems can be unnecessary. We demonstrate our system both on standard benchmarks and on the real-world data sets that motivated this work.
Ground fluidization promotes rapid running of a lightweight robot
Authors: Zhang Tingnan , Qian Feifei , Li Chen , Masarati Pierangelo , Hoover Aaron M. , Birkmeyer Paul , Pullin Andrew , Fearing Ronald S. , Goldman Daniel I.
Published: July 2013

We study the locomotor mechanics of a small, lightweight robot (DynaRoACH, 10 cm, 25 g) which can move on a granular substrate of 3 mm diameter glass particles at speeds up to 5 body length/s, approaching the performance of certain desert-dwelling animals. To reveal how the robot achieves this performance, we used high-speed imaging to capture its kinematics, and developed a numerical multi-body simulation of the robot coupled to an experimentally validated simulation of the granular medium. Average speeds measured in experiment and simulation agreed well, and increased nonlinearly with stride frequency, reflecting a change in propulsion mode. At low frequencies, the robot used a quasi-static “rotary walking” mode, in which the substrate yielded as legs penetrated and then solidified once vertical force balance was achieved. At high frequencies the robot propelled itself using the speed-dependent fluid-like inertial response of the material. The simulation allows variation of parameters which are inconvenient to modify in experiment, and thus gives insight into how substrate and robot properties change performance. Our study reveals how lightweight animals can achieve high performance on granular substrates; such insights can advance the design and control of robots in deformable terrains.
Thoughts About Conceptual Models, Theories, and Literature Reviews
Authors: Fawcett Jacqueline
Published: July 2013

This essay focuses on various types of literature reviews, including scoping reviews, realist reviews, and integrative reviews. As contributions to understanding the state of nursing science about a particular topic, each literature review should be but rarely is guided by a nursing conceptual model, and the research findings should be but rarely are interpreted as theories that were generated or tested. Examples that are exceptions to usual literature reviews are given.
A Different Drum
Authors: McGarry Julie , Aubeeluck Aimee
Published: July 2013

The authors in this article describe the background and development of a drama-based educational initiative for student nurses in the United Kingdom (UK) Forty-five student nurses from Adult and Mental-Health fields of study took part in a one-day experience where they worked alongside individuals with learning disabilities to produce art, dance, and drama sketches. The workshop was evaluated using a validated questionnaire to explore the experience from the students’ perspectives. Students felt challenged as they were pushed beyond the comfort zone of a regular classroom environment. Moreover, a greater understanding of core concepts such as empathy, dignity, stigma, and social exclusion were identified as key outcomes of the experience. The focus for future work in this field is to explore the ways in which arts-based learning and teaching initiatives can be developed within mainstream curricula.
Limitations of current treatments for systemic lupus erythematosus: a patient and physician survey
Authors: Strand V , Galateanu C , Pushparajah DS , Nikaï E , Sayers J , Wood R , Vollenhoven RF van
Published: July 2013

An independent cross-sectional survey assessed systemic lupus erythematosus (SLE) disease and treatment burden. Variables included medication classes prescribed, disease activity, flare occurrences, treatment satisfaction, and validated measures of health-related quality of life (HRQoL), fatigue and work productivity. Of 886 eligible patients (mean age 41.3 years, 89% female), 515 completed the survey. One-third reported moderate-to-severe disease activity, and 31% had flared in the last 12 months. Higher severity of disease activity (moderate-to-severe) was associated with ≥2 medication classes prescribed and treatment regimens that included corticosteroids (CS) (both p < 0.0001). Patients receiving CS reported lower EQ-5D scores ( p = 0.0019) and higher fatigue levels ( p < 0.001), and both patients ( p = 0.0019) and physicians ( p = 0.0001) were less likely to report satisfaction with treatment regimens including CS. Among responders eligible for work ( n = 456), severity of disease activity (moderate-to-severe vs. mild) was associated with unemployment (52.9% vs. 40.8%; p = 0.0189), greater impairment in work productivity (36% vs. 21%; p = 0.0003) and participation in daily activities (41% vs. 21%; p < 0.0001). This survey confirms that SLE and current treatment options substantially impair patients' health status and work productivity. Physician- and patient-reported satisfaction with current treatment regimens, despite poorly controlled disease activity, indicate they are resigned to the limitations of available SLE treatment regimens.
Aspirin resistance in systemic lupus erythematosus. A pilot study
Authors: Akdogan A , Kilic L , Akman U , Dogan I , Karadag O , Bilgen SA , Buyukasik Y , Kiraz S , Ertenli I
Published: July 2013

Systemic lupus erythematosus (SLE) patients are at increased risk of thrombosis and cardiovascular diseases. Aspirin is an effective treatment option for these patients. The aim of this study was to investigate the presence of aspirin resistance in SLE patients. We studied aspirin resistance in 33 SLE patients and nine healthy controls by using a Multiplate® impedance aggregometer (Dynabyte GmbH, Munich, Germany). Twenty-six SLE patients were on regular aspirin treatment. Aspirin resistance was found in five (19.2%) out of 26 patients who were on aspirin treatment. When the tests were repeated by adding acetylsalicylic acid in the medium, all of these patients became responsive to the aspirin. SLE disease activity, body mass index, smoking status, and the presence of anticardiolipin antibodies or positive lupus anticoagulant test results were no different in patients with or without aspirin resistance. ( p > 0.05 for all). Our results suggest that there may be a considerable number of SLE patients with aspirin resistance.
Inequality estimates for the boundedness of multilinear singular and fractional integral operators
Authors: Zhou Xiaosha , Huang Chuangxia , Hu Haijun , Liu Li
Published: July 2013

In this paper, the inequality of boundedness for the multilinear fractional singular integral operators associated to the weighted Lipschitz functions is estimated. The operators include the Calderón-Zygmund singular integral operator and the fractional integral operator.

MSC:42B20, 42B25.
Mitofusion-2-mediated alleviation of insulin resistance in rats through reduction in lipid intermediate accumulation in skeletal muscle
Authors: Zhang Xuemei , Wang Chao , Song Guangyao , Gan Kexin , Kong Dexian , Nie Qian , Ren Luping
Published: July 2013

Background

Increased lipid accumulation and mitochondrial dysfunction within skeletal muscle have been shown to be strongly associated with insulin resistance. However, the role of mitofusion-2 (MFN2), a key factor in mitochondrial function and energy metabolism, in skeletal muscle lipid intermediate accumulation remains to be elucidated.

Results

A high-fat diet resulted in insulin resistance as well as accumulation of cytosolic lipid intermediates and down-regulation of MFN2 and CPT1 in skeletal muscle in rats, while MFN2 overexpression improved insulin sensitivity and reduced lipid intermediates in muscle, possibly by upregulation of CPT1 expression.

Conclusions

MFN2 overexpression can rescue insulin resistance, possibly by upregulating CPT1 expression leading to reduction in the accumulation of lipid intermediates in skeletal muscle. These observations contribute to the investigations of new diabetes therapies.
Chronic glucolipotoxic conditions in pancreatic islets impair insulin secretion due to dysregulated calcium dynamics, glucose responsiveness and mitochondrial activity
Authors: Somesh Baggavalli P , Verma Mahesh Kumar , Sadasivuni Manoj Kumar , Mammen-Oommen Anup , Biswas Sanghamitra , Shilpa Pavagada C , Reddy Ashok Kumar , Yateesh Aggunda N , Pallavi Puttrevana M , Nethra Siddaraju , Smitha Rachapalli , Neelima Korrapati , Narayanan Usha , Jagannath Madanahalli R
Published: July 2013

Background

In the progression towards diabetes, glucolipotoxicity is one of the main causes of pancreatic beta cell pathology. The aim of this study was to examine the in vitro effects of chronic glucolipotoxic conditions on cellular responses in pancreatic islets, including glucose and fat metabolism, Calcium mobilization, insulin secretion and insulin content.

Results

Exposure of islets to chronic glucolipotoxic conditions decreased glucose stimulated insulin secretion in vitro. Reduced protein levels of Glut2/slc2a2, and decreased glucokinase and pyruvate carboxylase mRNA levels indicated a significant lowering in glucose sensing. Concomitantly, both fatty acid uptake and triglyceride accumulation increased significantly while fatty acid oxidation decreased. This general suppression in glucose metabolism correlated well with a decrease in mitochondrial number and activity, reduction in cellular ATP content and dampening of the TCA cycle. Further, we also observed a decrease in IP3 levels and lower Calcium mobilization in response to glucose. Importantly, chronic glucolipotoxic conditions in vitro decreased insulin gene expression, insulin content, insulin granule docking (to the plasma membrane) and insulin secretion.

Conclusions

Our results present an integrated view of the effects of chronic glucolipotoxic conditions on known and novel signaling events, in vitro, that results in reduced glucose responsiveness and insulin secretion.
Overexpression of peptide deformylase in breast, colon, and lung cancers
Authors: Randhawa Harsharan , Chikara Shireen , Gehring Drew , Yildirim Tuba , Menon Jyotsana , Reindl Katie M
Published: July 2013

Background

Human mitochondrial peptide deformylase (PDF) has been proposed as a novel cancer therapeutic target. However, very little is known about its expression and regulation in human tissues. The purpose of this study was to characterize the expression pattern of PDF in cancerous tissues and to identify mechanisms that regulate its expression.

Methods

The mRNA expression levels of PDF and methionine aminopeptidase 1D (MAP1D), an enzyme involved in a related pathway with PDF, were determined using tissue panels containing cDNA from patients with various types of cancer (breast, colon, kidney, liver, lung, ovarian, prostate, or thyroid) and human cell lines. Protein levels of PDF were also determined in 2 colon cancer patients via western blotting. Colon cancer cells were treated with inhibitors of ERK, Akt, and mTOR signaling pathways and the resulting effects on PDF and MAP1D mRNA levels were determined by qPCR for colon and lung cancer cell lines. Finally, the effects of a PDF inhibitor, actinonin, on the proliferation of breast, colon, and prostate cell lines were determined using the CyQUANT assay.

Results

PDF and MAP1D mRNA levels were elevated in cancer cell lines compared to non-cancer lines. PDF mRNA levels were significantly increased in breast, colon, and lung cancer samples while MAP1D mRNA levels were increased in just colon cancers. The expression of PDF and MAP1D varied with stage in these cancers. Further, PDF protein expression was elevated in colon cancer tissue samples. Inhibition of the MEK/ERK, but not PI3K or mTOR, pathway reduced the expression of PDF and MAP1D in both colon and lung cancer cell lines. Further, inhibition of PDF with actinonin resulted in greater reduction of breast, colon, and prostate cancer cell proliferation than non-cancer cell lines.

Conclusions

This is the first report showing that PDF is over-expressed in breast, colon, and lung cancers, and the first evidence that the MEK/ERK pathway plays a role in regulating the expression of PDF and MAP1D. The over-expression of PDF in several cancers and the inhibition of cancer cell growth by a PDF inhibitor suggest this enzyme may act as an oncogene to promote cancer cell proliferation.
Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation: PROTON-trial
Authors: Arshad Freeha , Ickx Brigitte , van Beem Rachel T , Polak Wojciech , Grüne Frank , Nevens Frederik , Ilmakunnas Minna , Koivusalo Anna-Maria , Isoniemi Helena , Strengers Paul FW , Groen Henk , Hendriks Herman GD , Lisman Ton , Pirenne Jacques , Porte Robert J
Published: July 2013

Background

In patients with cirrhosis, the synthesis of coagulation factors can fall short, reflected by a prolonged prothrombin time. Although anticoagulants factors are decreased as well, blood loss during orthotopic liver transplantation can still be excessive. Blood loss during orthotopic liver transplantation is currently managed by transfusion of red blood cell concentrates, platelet concentrates, fresh frozen plasma, and fibrinogen concentrate. Transfusion of these products may paradoxically result in an increased bleeding tendency due to aggravated portal hypertension. The hemostatic effect of these products may therefore be overshadowed by bleeding complications due to volume overload.

In contrast to these transfusion products, prothrombin complex concentrate is a low-volume highly purified concentrate, containing the four vitamin K dependent coagulation factors. Previous studies have suggested that administration of prothrombin complex concentrate is an effective method to normalize a prolonged prothrombin time in patients with liver cirrhosis. We aim to investigate whether the pre-operative administration of prothrombin complex concentrate in patients undergoing liver transplantation for end-stage liver cirrhosis, is a safe and effective method to reduce perioperative blood loss and transfusion requirements.

Methods/Design

This is a double blind, multicenter, placebo-controlled randomized trial.

Cirrhotic patients with a prolonged INR (≥1.5) undergoing liver transplantation will be randomized between placebo or prothrombin complex concentrate administration prior to surgery. Demographic, surgical and transfusion data will be recorded. The primary outcome of this study is RBC transfusion requirements.

Discussion

Patients with advanced cirrhosis have reduced plasma levels of both pro- and anticoagulant coagulation proteins. Prothrombin complex concentrate is a low-volume plasma product that contains both procoagulant and anticoagulant proteins and transfusion will not affect the volume status prior to the surgical procedure. We hypothesize that administration of prothrombin complex concentrate will result in a reduction of perioperative blood loss and transfusion requirements. Theoretically, the administration of prothrombin complex concentrate may be associated with a higher risk of thromboembolic complications. Therefore, thromboembolic complications are an important secondary endpoint and the occurrence of this type of complication will be closely monitored during the study.

Trial registration

The trial is registered at http://www.trialregister.nl with number NTR3174. This registry is accepted by the ICMJE.
Antimicrobial activity and rutin identification of honey produced by the stingless bee Melipona compressipes manaosensis and commercial honey
Authors: Pimentel Renah Boanerges de Queiroz , da Costa Cristovão Alves , Albuquerque Patrícia Melchionna , Junior Sergio Duvoisin
Published: July 2013

Background

Honey has been identified as a potential alternative to the widespread use of antibiotics, which are of significant concern considering the emergence of resistant bacteria. In this context, this study aimed to evaluate the antimicrobial activity of honey samples produced by a stingless bee species and by Apis sp. against pathogenic bacteria, as well as to identify the presence of phenolic compounds.

Methods

Honey samples from the stingless bee M. compressipes manaosensis were collected twice, during the dry and rainy seasons. Three commercial honey samples from Apis sp. were also included in this study. Two different assays were performed to evaluate the antibacterial potential of the honey samples: agar-well diffusion and broth macrodilution. Liquid-liquid extraction was used to assess phenolic compounds from honey. HPLC analysis was performed in order to identify rutin and apigenin on honey samples. Chromatograms were recorded at 340 and 290 nm.

Results

Two honey samples were identified as having the highest antimicrobial activity using the agar diffusion method. Honey produced by Melipona compressipes manaosensis inhibited the growth of Staphylococcus aureus, Escherichia coli (0157: H7), Proteus vulgaris, Shigella sonnei and Klebsiella sp. A sample of honey produced by Apis sp. also inhibited the growth of Salmonella paratyphi. The macrodilution technique presented greater sensitivity for the antibacterial testing, since all honey samples showed activity. Flavonoid rutin was identified in the honey sample produced by the stingless bee.

Conclusions

Honey samples tested in this work showed antibacterial activity against Gram-positive and Gram-negative bacteria. The results reported herein highlight the potential of using honey to control bacterial growth.
Changes in the burden of malaria following scale up of malaria control interventions in Mutasa District, Zimbabwe
Authors: Mharakurwa Sungano , Mutambu Susan L , Mberikunashe Joseph , Thuma Philip E , Moss William J , Mason Peter R ,   for the Southern Africa ICEMR Team
Published: July 2013

Background

To better understand trends in the burden of malaria and their temporal relationship to control activities, a survey was conducted to assess reported cases of malaria and malaria control activities in Mutasa District, Zimbabwe.

Methods

Data on reported malaria cases were abstracted from available records at all three district hospitals, three rural hospitals and 25 rural health clinics in Mutasa District from 2003 to 2011.

Results

Malaria control interventions were scaled up through the support of the Roll Back Malaria Partnership, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and The President’s Malaria Initiative. The recommended first-line treatment regimen changed from chloroquine or a combination of chloroquine plus sulphadoxine/pyrimethamine to artemisinin-based combination therapy, the latter adopted by 70%, 95% and 100% of health clinics by 2008, 2009 and 2010, respectively. Diagnostic capacity improved, with rapid diagnostic tests (RDTs) available in all health clinics by 2008. Vector control consisted of indoor residual spraying and distribution of long-lasting insecticidal nets. The number of reported malaria cases initially increased from levels in 2003 to a peak in 2008 but then declined 39% from 2008 to 2010. The proportion of suspected cases of malaria in older children and adults remained high, ranging from 75% to 80%. From 2008 to 2010, the number of RDT positive cases of malaria decreased 35% but the decrease was greater for children younger than five years of age (60%) compared to older children and adults (26%).

Conclusions

The burden of malaria in Mutasa District decreased following the scale up of malaria control interventions. However, the persistent high number of cases in older children and adults highlights the need for strategies to identify locally effective control measures that target all age groups.
Dependencies of microstructure and stress on the thickness of GdBa2Cu3O7 − δ thin films fabricated by RF sputtering
Authors: Wang Ying , Xu Da , Li Yijie , Liu Linfei
Published: July 2013

GdBa2Cu3O7 − δ
(GdBCO) films with different thicknesses from 200 to 2,100 nm are deposited on CeO2/yttria-stabilized zirconia (YSZ)/CeO2-buffered Ni-W substrates by radio-frequency magnetron sputtering. Both the X-ray diffraction and scanning electron microscopy analyses reveal that the a-axis grains appear at the upper layers of the films when the thickness reaches to 1,030 nm. The X-ray photoelectron spectroscopy measurement implies that the oxygen content is insufficient in upper layers beyond 1,030 nm for a thicker film. The Williamson-Hall method is used to observe the variation of film stress with increasing thickness of our films. It is found that the highest residual stresses exist in the thinnest film, while the lowest residual stresses exist in the 1,030-nm-thick film. With further increasing film thickness, the film residual stresses increase again. However, the critical current (I
c) of the GdBCO film first shows a nearly linear increase and then shows a more slowly enhancing to a final stagnation as film thickness increases from 200 to 1,030 nm and then to 2,100 nm. It is concluded that the roughness and stress are not the main reasons which cause the slow or no increase in I
c. Also, the thickness dependency of GdBa2Cu3O7 − δ
films on the I
c is attributed to three main factors: a-axis grains, gaps between a-axis grains, and oxygen deficiency for the upper layers of a thick film.
Effect of lingual plates on generating intra-oral pressure during swallowing: an experimental study in healthy subjects
Authors: Hori Kazuhiro , Srinivasan Murali , Barbezat Cindy , Tamine Ken-ichi , Ono Takahiro , Müller Frauke
Published: July 2013

Background

Although palatal augmentation prostheses (PAPs) can improve dysphagia, their application is compromised in the absence of maxillary abutment teeth. Experimental lingual plates (ELPs) used for raising the tongue may be employed as alternative to PAPs.

Methods

Influence of different ELP designs, plateau (P–type) and drop-shaped (D–type), on the intra–oral pressure during swallowing were tested. Eleven healthy dentate volunteers, with a mean age of 35.5±10.5 years, participated in this study. Tongue pressure on the hard palate was measured using an ultra-thin sensor sheet with five measuring points, whilst performing dry, 5–ml and 15–ml water swallows, with and without the ELPs in situ. Additional pressure sensors were installed in the lingual aspects of the ELPs, and on the vestibular aspect of the lower molars for measuring sublingual and oral vestibule pressures, respectively. Each measurement was recorded thrice. A repeated measures ANOVA was employed to verify differences in duration, maximal magnitude and integrated value for the different experimental situations. Tukey’s post hoc test was performed for comparison testing. Statistical significance was set at p<0.05.

Results

The sequence of tongue–palate contact on the median line of the hard palate without ELPs was maintained, except for the 15 ml P–type swallow. Tongue pressure started earlier with the D–type but reached its peak nearly at the same time as without ELPs. The peak magnitude and cumulative tongue pressure against the hard palate decreased by wearing ELPs (p<0.05), but was inconsistent between the two types of ELPs and for the different swallowing volumes. Both, maximum and cumulative vestibular pressures were mostly similar or larger with P–type than that with D–type.

Conclusion

D-type and P-type ELPs seem to have the inverse effect of PAPs on the palatal tongue pressure during swallowing. These first counterintuitive findings do not yet justify rejecting the basic rationale of using ELPs for the treatment of dysphagia; hence a rather biologically designed piezographic lingual plate may be more appropriate.
Brain microglia were activated in sporadic CJD but almost unchanged in fatal familial insomnia and G114V genetic CJD
Authors: Shi Qi , Xie Wu-Ling , Zhang BaoYun , Chen Li-Na , Xu Yin , Wang Ke , Ren Ke , Zhang Xiao-Mei , Chen Cao , Zhang Jin , Dong Xiao-Ping
Published: July 2013

Background

Microglial activations have been described in different subtypes of human prion diseases such as sporadic Creutzfeldt-Jakob disease (CJD), variant CJD, Kuru and Gerstmann-Sträussler-Scheinker disease (GSS). However, the situation of microglia in other genetic prion diseases such as fatal familial insomnia (FFI) and familial CJD remains less understood. The brain microglia was evaluated comparatively between the FFI, G114V and sCJD cases in the study.

Methods

Specific Western blots, immunohistochemical and immunofluorescent assays were used to detect the changes of microglia and ELISA tests were used for levels of inflammatory cytokines.

Results

Western blots, immunohistochemical and immunofluorescent assays illustrated almost unchanged microglia in the temporal lobes of FFI and G114V gCJD, but obviously increased in those of sCJD. The Iba1-levels maintained comparable in six different brain regions of FFI and G114V cases, including thalamus, cingulate gyrus, frontal cortex, parietal cortex, occipital cortex and temporal cortex. ELISA tests for inflammatory cytokines revealed significantly up-regulated IL-1β, IL-6 and TNF-α in the brain homogenates from sCJD, but not in those from FFI and G114V gCJD.

Conclusion

Data here demonstrates silent brain microglia in FFI and G114V gCJD but obviously increased in sCJD, which reflects various pathogenesis of different human prion diseases subtypes.
Analgesic Effect of a Mixed T-Type Channel Inhibitor/CB2 Receptor Agonist
Authors: Gadotti Vinicius M , You Haitao , Petrov Ravil R , Berger N Daniel , Diaz Philippe , Zamponi Gerald W
Published: July 2013

Background

Cannabinoid receptors and T-type calcium channels are potential targets for treating pain. Here we report on the design, synthesis and analgesic properties of a new mixed cannabinoid/T-type channel ligand, NMP-181.

Results

NMP-181 action on CB1 and CB2 receptors was characterized in radioligand binding and in vitro GTPγ[35S] functional assays, and block of transiently expressed human Cav3.2 T-type channels by NMP-181 was analyzed by patch clamp. The analgesic effects and in vivo mechanism of action of NMP-181 delivered spinally or systemically were analyzed in formalin and CFA mouse models of pain. NMP-181 inhibited peak Cav3.2 currents with IC50 values in the low micromolar range and acted as a CB2 agonist. Inactivated state dependence further augmented the inhibitory action of NMP-181. NMP-181 produced a dose-dependent antinociceptive effect when administered either spinally or systemically in both phases of the formalin test. Both i.t. and i.p. treatment of mice with NMP-181 reversed the mechanical hyperalgesia induced by CFA injection. NMP-181 showed no antinocieptive effect in Cav3.2 null mice. The antinociceptive effect of intrathecally delivered NMP-181 in the formalin test was reversed by i.t. treatment of mice with AM-630 (CB2 antagonist). In contrast, the NMP-181-induced antinociception was not affected by treatment of mice with AM-281 (CB1 antagonist).

Conclusions

Our work shows that both T-type channels as well as CB2 receptors play a role in the antinociceptive action of NMP-181, and also provides a novel avenue for suppressing chronic pain through novel mixed T-type/cannabinoid receptor ligands.
Mutually dependent degradation of Ama1p and Cdc20p terminates APC/C ubiquitin ligase activity at the completion of meiotic development in yeast
Authors: Tan Grace S , Lewandowski Rebecca , Mallory Michael J , Strich Randy , Cooper Katrina F
Published: July 2013

Background

The execution of meiotic nuclear divisions in S. cerevisiae is regulated by protein degradation mediated by the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase. The correct timing of APC/C activity is essential for normal chromosome segregation. During meiosis, the APC/C is activated by the association of either Cdc20p or the meiosis-specific factor Ama1p. Both Ama1p and Cdc20p are targeted for degradation as cells exit meiosis II with Cdc20p being destroyed by APC/CAma1. In this study we investigated how Ama1p is down regulated at the completion of meiosis.

Findings

Here we show that Ama1p is a substrate of APC/CCdc20 but not APC/CCdh1 in meiotic cells. Cdc20p binds Ama1p in vivo and APC/CCdc20 ubiquitylates Ama1p in vitro. Ama1p ubiquitylation requires one of two degradation motifs, a D-box and a “KEN-box” like motif called GxEN. Finally, Ama1p degradation does not require its association with the APC/C via its conserved APC/C binding motifs (C-box and IR) and occurs simultaneously with APC/CAma1-mediated Cdc20p degradation.

Conclusions

Unlike the cyclical nature of mitotic cell division, meiosis is a linear pathway leading to the production of quiescent spores. This raises the question of how the APC/C is reset prior to spore germination. This and a previous study revealed that Cdc20p and Ama1p direct each others degradation via APC/C-dependent degradation. These findings suggest a model that the APC/C is inactivated by mutual degradation of the activators. In addition, these results support a model in which Ama1p and Cdc20p relocate to the substrate address within the APC/C cavity prior to degradation.
Circulating miRNAs reflect early myocardial injury and recovery after heart transplantation
Authors: Wang Enshi , Nie Yu , Zhao Qian , Wang Wei , Huang Jie , Liao Zhongkai , Zhang Hao , Hu Shengshou , Zheng Zhe
Published: July 2013

Background

MicroRNAs (miRNAs) are short, single-stranded and non-coding RNAs, freely circulating in human plasma and correlating with vary pathologies. In this study, we monitored early myocardial injury and recovery after heart transplantation by detecting levels of circulating muscle-specific miR-133a, miR-133b and miR-208a.

Methods

7 consecutive patients underwent heart transplantation in Fuwai hospital and 14 healthy controls were included in our study. Peripheral vein blood was drawn from patients on the day just after transplantation (day 0), the 1st, 2nd, 3rd, 7th and 14th day after transplantation respectively. Serum from peripheral blood was obtained for cardiac troponin I (cTnI) measurement. Plasma was centrifuged from peripheral blood for measuring miR-133a, miR-133b and miR-208a by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The plasma concentration of miRNAs were calculated by absolute quantification method. The sensitivity and specificity of circulating miRNAs were revealed by receiver operating characteristic curve (ROC) analysis. Correlations between miRNAs and cTnI / perioperative parameters were analyzed.

Results

Similar to cTnI, miR-133a, miR-133b and miR-208a all showed dynamic changes from high to low levels early after operation. The Sensitivity and specificity of miRNAs were: miR-133a (85.7%,100%), miR-208a (100%,100%), and miR-133b (90%,100%). Correlations between miRNAs and cTnI were statistically significant (p < 0.05), especially for miR-133b (R2 = 0.813, p < 0.001). MiR-133b from Day 0-Day 2 (r > 0.98, p < 0.01), and cTnI from Day 1- Day 3 (r > 0.86, p < 0.05) had strong correlations with bypass time, particularly parallel bypass time. Obviously, miR-133b had a better correlation than cTnI. Circulating miR-133b correlated well with parameters of heart function such as central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO) and inotrope support, while cTnI only correlated with 3 of the 4 parameters mentioned above. MiR-133b also had strong correlations with ventilation time (r > 0.99, p < 0.001) and length of ICU stay (r > 0.92, p < 0.05), both of which reflected the recovery after operation. The correlation coefficients of miR-133b were also higher than that of cTnI.

Conclusions

The dynamic change in circulating muscle-specific miRNAs, especially miR-133b can reflect early myocardial injury after heart transplantation. And miR-133b may have advantages over cTnI in forecasting graft dysfunction and recovery of patients after operation.
Bacterial bioaugmentation for improving methane and hydrogen production from microalgae
Authors: Lü Fan , Ji Jiaqi , Shao Liming , He Pinjing
Published: July 2013

Background

The recalcitrant cell walls of microalgae may limit their digestibility for bioenergy production. Considering that cellulose contributes to the cell wall recalcitrance of the microalgae Chlorella vulgaris, this study investigated bioaugmentation with a cellulolytic and hydrogenogenic bacterium, Clostridium thermocellum, at different inoculum ratios as a possible method to improve CH4 and H2 production of microalgae.

Results

Methane production was found to increase by 17?~?24% with the addition of C. thermocellum, as a result of enhanced cell disruption and excess hydrogen production. Furthermore, addition of C. thermocellum enhanced the bacterial diversity and quantities, leading to higher fermentation efficiency. A two-step process of addition of C. thermocellum first and methanogenic sludge subsequently could recover both hydrogen and methane, with a 9.4% increase in bioenergy yield, when compared with the one-step process of simultaneous addition of C. thermocellum and methanogenic sludge. The fluorescence peaks of excitation-emission matrix spectra associated with chlorophyll can serve as biomarkers for algal cell degradation.

Conclusions

Bioaugmentation with C. thermocellum improved the degradation of C. vulgaris biomass, producing higher levels of methane and hydrogen. The two-step process, with methanogenic inoculum added after the hydrogen production reached saturation, was found to be an energy-efficiency method for hydrogen and methane production.
Epidemiological profile of Clonorchis sinensis infection in one community, Guangdong, People’s Republic of China
Authors: Qian Men-Bao , Chen Ying-Dan , Fang Yue-Yi , Tan Tan , Zhu Ting-Jun , Zhou Chang-Hai , Wang Guo-Fei , Xu Long-Qi , Zhou Xiao-Nong
Published: July 2013

Background

Clonorchiasis caused by ingesting improperly prepared fish ranks among the most important but still neglected food-borne parasitic diseases, especially in the People’s Republic of China (P.R. China). To promote the implementation of interventions efficiently, the demonstration of an epidemiological profile of Clonorchis sinensis infection is essential in hyper-epidemic areas.

Methods

In one community with higher levels of economic development in Guangdong province, P.R. China, villagers were motivated to provide stool samples for examining helminth eggs. Then, those infected with C. sinensis completed the structured questionnaire including demographical characteristics, knowledge and behavior.

Results

A total of 293 villagers infected with C. sinensis participated in questionnaire investigation. Among them, 94.54% were adult and 93.17% were indigenous. The geometric mean of C. sinensis eggs per gram of feces in the children, adult females and adult males was 58, 291 and 443, respectively. The divergence between knowledge and behavior in the adults, especially the adult males, was shown. Out of 228 persons eating raw fish, 160 did it more frequently at restaurants, the proportion of which varied in different populations, showing 25.00%, 54.88% and 80.28% in the children, adult females and adult males, respectively.

Conclusions

Different interventions need to be adopted in different populations. Chemotherapy should be prioritized in the adults, especially the adult males. In addition, health education targeting the children, is essential and may play a crucial role in controlling clonorchiasis in the long term. In order to successfully control clonorchiasis, intervention in the restaurant should not be overlooked in some endemic areas.
Pleiotropic effects of rosuvastatin on the glucose metabolism and the subcutaneous and visceral adipose tissue behavior in C57Bl/6 mice
Authors: Neto-Ferreira Rodrigo , Rocha Vinícius Novaes , Souza-Mello Vanessa , Mandarim-de-Lacerda Carlos Alberto , de Carvalho Jorge José
Published: July 2013

The aim of this study was to evaluate whether rosuvastatin (HMG-CoA reductase inhibitor) modulates the carbohydrate and lipid metabolism, the development of non-alcoholic fatty liver disease (NAFLD), and the increase in body mass in a model of diet-induced obesity. Male C57Bl/6 mice (3-months-old) were fed a high-fat diet (HF, 60% lipids) or the standard chow (SC, 10% lipids) for 15 weeks. The animals were then treated with 10 mg/kg/day (HF-R10 group), 20 mg/kg/day (HF-R20), or 40 mg/kg/day (HF-R40) of rosuvastatin for five weeks. The HF diet led to glucose intolerance, insulin resistance, weight gain, increased visceral adiposity with adipocyte hypertrophy, and hepatic steatosis (micro and macrovesicular). The rosuvastatin treatment decreased the adiposity and the adipocyte size in the HF-R10 and HF-R20 groups. In addition, rosuvastatin changed the pattern of fat distribution in the HF-R40 group because more fat was stored subcutaneously than in visceral depots. This redistribution improved the fasting glucose and the glucose intolerance. Rosuvastatin also improved the liver morphology and ultrastructure in a dose-dependent manner. In conclusion, rosuvastatin exerts pleiotropic effects through a dose-dependent improvement of glucose intolerance, insulin sensitivity and NAFLD and changes the fat distribution from visceral to subcutaneous fat depots in a mouse model of diet-induced obesity.
Increased gene expression of FOXP1 in patients with autism spectrum disorders
Authors: Chien Wei-Hsien , Gau SusanShur-Fen , Chen Chun-Houh , Tsai Wen-Che , Wu Yu-Yu , Chen Po-Hsu , Shang Chi-Yung , Chen Chia-Hsiang
Published: July 2013

Background

Comparative gene expression profiling analysis is useful in discovering differentially expressed genes associated with various diseases, including mental disorders. Autism spectrum disorders (ASD) are a group of complex childhood-onset neurodevelopmental and genetic disorders characterized by deficits in language development and verbal communication, impaired reciprocal social interaction, and the presence of repetitive behaviors or restricted interests. The study aimed to identify novel genes associated with the pathogenesis of ASD.

Methods

We conducted comparative total gene expression profiling analysis of lymphoblastoid cell lines (LCL) between 16 male patients with ASD and 16 male control subjects to screen differentially expressed genes associated with ASD. We verified one of the differentially expressed genes,FOXP1, using real-time quantitative PCR (RT-qPCR) in a sample of 83 male patients and 83 male controls that included the initial 16 male patients and male controls, respectively.

Results

A total of 252 differentially expressed probe sets representing 202 genes were detected between the two groups, including 89 up- and 113 downregulated genes in the ASD group. RT-qPCR verified significant elevation of theFOXP1gene transcript of LCL in a sample of 83 male patients (10.46 ± 11.34) compared with 83 male controls (5.17 ± 8.20,P= 0.001).

Conclusions

Comparative gene expression profiling analysis of LCL is useful in discovering novel genetic markers associated with ASD. Elevated gene expression ofFOXP1might contribute to the pathogenesis of ASD.

Clinical trial registration

Identifier:NCT00494754
A simple strategy for heritable chromosomal deletions in zebrafish via the combinatorial action of targeting nucleases
Authors: Lim Shimin , Wang Yin , Yu Xueyao , Huang Yian , Featherstone Mark S , Sampath Karuna
Published: July 2013

Precise and effective genome-editing tools are essential for functional genomics and gene therapy. Targeting nucleases have been successfully used to edit genomes. However, whole-locus or element-specific deletions abolishing transcript expression have not previously been reported. Here, we show heritable targeting of locus-specific deletions in the zebrafish nodal-related genes squint (sqt) and cyclops (cyc). Our strategy of heritable chromosomal editing can be used for disease modeling, analyzing gene clusters, regulatory regions, and determining the functions of non-coding RNAs in genomes.
Suicide mitigation: a compassionate approach to suicide prevention
Authors: Cole-King Alys , Green Gill , Gask Linda , Hines Kevin , Platt Stephen
Published: July 2013

The death of a patient by suicide can severely affect mental health professionals, particularly if it occurs despite major efforts to intervene. Notwithstanding the difficulties faced by clinicians, suicide prevention remains of paramount importance in order to help save lives. This article seeks to promote a pragmatic and compassionate biopsychosocial response using evidence-based interventions to reduce suicide. It introduces practical strategies that psychiatrists can use in everyday clinical practice, in particular the paradigm shift of suicide mitigation to help prevent suicide. We believe that every encounter with a suicidal person is an opportunity to intervene to reduce their distress and, potentially, to save a life. We believe that it is no longer acceptable for clinicians to state that if patients wish to kill themselves they can do so, in the absence of any attempt at a compassionate intervention.
Boredom among psychiatric in-patients: does it matter?
Authors: Steele Rachel , Henderson Paul , Lennon Frances , Swinden Donna
Published: July 2013

Many psychiatric in-patients report boredom. Such complaints may appear trivial, but this literature review by a clinical librarian suggests that boredom is more complex than may initially appear and relates to wider areas of importance for in-patient psychiatric teams. Boredom may relate to the internal experience of meaning, which itself encompasses meaningful relationships and roles and a sense of control. Although meaningful therapeutic activities are vital, mental health professionals should focus on the internal as well as the external dimensions of boredom. Medications, particularly dopamine antagonist antipsychotics, may be a contributing factor. This article highlights the benefits of the clinical librarian role in synthesising research in mental health. Research can illuminate psychiatric practice in a more holistic way than purely by applying 'scientific' evidence in the practice of ‘biological’ psychiatry.
The Individual Recovery Outcomes Counter: preliminary validation of a personal recovery measure
Authors: Monger Bridey , Hardie Scott M. , Ion Robin , Cumming Jane , Henderson Nigel
Published: July 2013

Aims and method

The Individual Recovery Outcomes Counter (I.ROC) is to date the only recovery outcomes instrument developed in Scotland. This paper describes the steps taken to initially assess its validity and reliability, including factorial analysis, internal consistency and a correlation benchmarking analysis.

Results

The I.ROC tool showed high internal consistency. Exploratory factor analysis indicated a two-factor structure comprising intrapersonal recovery (factor 1) and interpersonal recovery (factor 2), explaining between them over 50% of the variance in I.ROC scores. There were no redundant items and all loaded on at least one of the factors. The I.ROC significantly correlated with widely used existing instruments assessing both personal recovery and clinical outcomes.

Clinical implications

I.ROC is a valid and reliable measure of recovery in mental health, preferred by service users when compared with well-established instruments. It could be used in clinical settings to map individual recovery, providing feedback for service users and helping to assess service outcomes.
Credit Risk and Disaster Risk
Authors: Gourio François
Published: July 2013

Credit spreads are large, volatile, and countercyclical, and recent empirical work suggests that risk premia, not expected credit losses, are responsible for these features. Building on the idea that corporate debt, while fairly safe in ordinary recessions, is exposed to economic depressions, this paper embeds a trade-off theory of capital structure into a real business cycle model with a small, exogenously timevarying risk of economic disaster. The model replicates the level, volatility and cyclicality of credit spreads, and variation in the corporate bond risk premium amplifies macroeconomic fluctuations in investment, employment, and GDP. (JEL E13, E22, E23, E24, E32, E44, G32)