bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review and meta-analysis of the effect of an ankle-foot orthosis on gait biomechanics after stroke
Authors: Tyson SF , Sadeghi-Demneh E , Nester CJ
Published: June 2013

Objective:

To systematically review the evidence on the effects of an ankle-foot orthosis on gait biomechanics after stroke

Data sources:

The following databases were searched; AMED, CINHAL, Cochrane Library (Stroke section), Medline, PubMed, Science Direct and Scopus. Previous reviews, reference lists and citation tracking of the selected articles were screened and the authors of selected trials contacted for any further unpublished data.

Review methods:

Controlled trials of an ankle-foot orthosis on gait biomechanics in stroke survivors were identified. A modified PEDro score evaluated trial quality; those scoring 4/8 or more were selected. Information on the trial design, population, intervention, outcomes, and mean and standard deviation values for the treatment and control groups were extracted. Continuous outcomes were pooled according to their mean difference and 95% confidence intervals in a fixed-effect model.

Results:

Twenty trials involving 314 participants were selected. An ankle-foot orthosis had a positive effect on ankle kinematics ( P < 0.00001–0.0002); knee kinematics in stance phase ( P < 0.0001–0.01); kinetics ( P = 0.0001) and energy cost ( P = 0.004), but not on knee kinematics in swing phase ( P = 0.84), hip kinematics ( P < 0.18–0.89) or energy expenditure ( P = 0.43). There were insufficient data for pooled analysis of individual joint moments, muscle activity or spasticity. All trials, except one, evaluated immediate effects only.

Conclusions:

An ankle-foot orthosis can improve the ankle and knee kinematics, kinetics and energy cost of walking in stroke survivors.
Lack of hemodynamic interaction between CGRP-receptor antagonist telcagepant (MK-0974) and sumatriptan: Results from a randomized study in patients with migraine
Authors: Depré M , MacLeod C , Palcza J , Behm MO , de Lepeleire I , Han T , Panebianco D , Smith WB , Blanchard R , Chodakewitz JA , Murphy MG , de Hoon JN
Published: June 2013

Objective

The objective of this article is to assess the effects of sumatriptan monotherapy, telcagepant monotherapy, and their combination on blood pressure (BP) in migraine patients during a headache-free period.

Methods

A double-blind, placebo-controlled, four-period, single-dose, randomized crossover study in 24 migraine patients was conducted. In each period, patients received a single oral dose of sumatriptan 100 mg alone, telcagepant 600 mg alone, sumatriptan 100 mg coadministered with telcagepant 600 mg, or placebo. Semi-recumbent BP was measured pre-dose and at seven post-dose timepoints over a period of six hours. Individual time-weighted averages in mean arterial pressure (MAP) were evaluated using a linear mixed-effects model. The pharmacokinetics of sumatriptan alone and in the presence of telcagepant were also evaluated using limited sampling times.

Results

The mean difference in time-weighted (0–2.5 h) MAP (90% confidence interval) was 1.2 mmHg (−0.2, 2.7) between telcagepant and placebo, 4.0 mmHg (2.5, 5.5) between sumatriptan and placebo, and 1.5 mmHg (0.0, 3.0) between telcagepant with sumatriptan vs sumatriptan alone. When coadministered with telcagepant, the AUC0–6h and Cmax of sumatriptan were increased by 23% and 24%, respectively. The small MAP increases observed after coadministration could possibly be associated with the slight elevations in sumatriptan levels.

Conclusion

Telcagepant does not elevate mean MAP, and coadministration of telcagepant with sumatriptan results in elevations in MAP similar to those observed following administration of sumatriptan alone in migraineurs during the interictal period. When coadministered, telcagepant slightly increases the plasma levels of sumatriptan, but without an apparent clinically meaningful effect.
Unraveling the Complex Nature of Mathematics Learning Disability
Authors: Watson Silvana M. R. , Gable Robert A.
Published: June 2013

In this article, we provide an overview of current knowledge on the underlying cognitive deficits associated with mathematics learning disabilities (MLD). We highlight difficulties surrounding the identification of MLD that include inconsistency in defining MLD, comorbidity with other disabilities, problems associated with assessment tools and actual skills measured, and the limited research on MLD. We offer suggestions for strengthening the research base, which in turn should contribute to improved outcomes for students with mathematics disabilities.
Amelioration of carbon tetrachloride-induced pulmonary toxicity with Oxalis corniculata
Authors: Ahmad Bushra , Khan Muhammad Rashid , Shah Naseer Ali
Published: June 2013

This research work was planned to investigate the antioxidant potential of methanolic crude extract of Oxalis corniculata (OCME) against lung injuries initiated by carbon tetrachloride (CCl4) in rats at histological and biochemical level. A total of 42 female Sprague Dawley rats were randomly distributed in to seven groups and each group comprised of six rats. Experiment was completed in 22 days (10 doses at alternate days). Group I was not treated (control rats), while group II was administered with vehicles (olive oil and dimethyl sulfoxide), groups III, IV, and V were treated with 1 ml kg−1 body weight (b.w.) of CCl4 (20% in olive oil). Group III received only CCl4, whereas groups IV and V were administered with 100 and 200 mg kg−1 b.w. of OCME, respectively. Group VI was administered with OCME (200 mg kg−1 b.w.) alone. Group VII was treated with sylimarin (50 mg kg−1 b.w.). CCl4 enhanced the lipid peroxidation while reduced the glutathione in lung samples. Activities of antioxidant enzymes, catalase, peroxidase, superoxide dismutase, and glutathione- S-transferase decreased in lung homogenates with CCl4. Treatment of CCl4 induced deleterious changes in the microanatomy of lungs by rupturing the alveolar septa, thickening of alveolar walls, and damaging the cells with subsequent collapse of blood vessels due to the accumulation of degenerated blood cells. OCME, dose dependently, prevented the alterations in these parameters. These results suggest that OCME protected the lungs due to its intrinsic properties by scavenging of free radicals generated by CCl4.
Synergistic effect of black tea and curcumin in improving the hepatotoxicity induced by aflatoxin B1 in rats
Authors: Alm-Eldeen Abeer A , Mona Mohamed H , Shati Ali A , El-Mekkawy Haitham I
Published: June 2013

Aflatoxin B1 (AFB1) is a toxic compound commonly found as a contaminant in human food. It is carcinogenic due its potential in inducing the oxidative stress and distortion of the most antioxidant enzymes. Since black tea possesses strong antioxidant activity, it protects cells and tissues against oxidative stress. Curcumin (CMN), a naturally occurring agent, has a combination of biological and pharmacological properties that include antioxidant activity. Therefore, the present study was carried out to investigate the possible role of separate and mixed supplementation of black tea extract and CMN in the hepatotoxicity induced by AFB1 in rats. A total of 48 adult male Sprague Dawley rats were randomly divided into eight groups with six rats in each group. Group 1 (normal control) includes rats that received no treatment. Groups 2, 3, and 4 (positive control) include rats that received olive oil, black tea extract, and CMN, respectively. Group 5 includes rats that received AFB1 at a dose of 750 μg/kg body weight (b.w.) dissolved in olive oil. Groups 6, 7, and 8 include rats that received AFB1 along with 2% black tea extract, CMN at a dose of 200 mg/kg b.w., and both black tea extract and CMN at the same previous doses, respectively. After 90 days, biochemical and histopathological examination was carried out for the blood samples and liver tissues. A significant decrease in the antioxidant enzymes and a significant increase in the lipid peroxidation and hydrogen peroxide in the rats treated with AFB1 were observed. Moreover, there were dramatic changes in the liver function biomarkers, lipid profile, and liver architecture. Supplementation of black tea extract or CMN showed an efficient role in repairing the distortion of the biochemical and histological changes induced by AFB1 in liver. This improvement was more pronounced when both CMN and black tea were used together.
Beyond Grantmaking
Authors: Quinn Rand , Tompkins-Stange Megan , Meyerson Debra
Published: June 2013

Studies examining the role of philanthropic foundations in advancing social change have primarily focused on the impact of foundations’ financial resources. Few scholars have analyzed how foundations also leverage social mechanisms to advance and legitimate desired change. We conceptualize philanthropic foundations as agents of change known as institutional entrepreneurs to illuminate the social mechanisms they employ in pursuit of institutional change. We study the case of charter schools within the field of U.S. public education, where foundations elevated a new organizational form—the charter management organization—by engaging in three social mechanisms: recombining cultural elements to establish the form, enforcing evaluative frameworks to assess the form, and sponsoring new professionals to populate the form with preferred expertise. We argue that foundations are distinctive due to their ability to simultaneously pursue social mechanisms that are often considered to be the realms of different types of institutional entrepreneurs.
Unsustainable employment portfolios
Authors: Buchanan John , Dymski Gary , Froud Julie , Johal Sukhdev , Leaver Adam , Williams Karel
Published: June 2013

This Debates and Controversies contribution introduces the notion of an employment portfolio to explore how economies create combinations of employment. It is not simply the number of jobs but the factor share distributed to labour and the sectoral mix and composition that matter. Three case studies of employment portfolio (Australia, California and the UK) are used to show how previous attempts at structural reform failed to deliver sustainable employment, even though economies need to offer a portfolio of jobs as a hedge against an uncertain future. The article argues that new ideas and non-standard policies are required to help create employment of sufficient quality and quantity in the current difficult conditions.
Approach to produce rigid closed-cell polyimide foams
Authors: Wang Leilei , Hu Aijun , Fan Lin , Yang Shiyong
Published: June 2013

A new chemical approach to prepare rigid closed-cell polyimide foams (PIFs) has been developed by thermal foaming of nadimide end-capped imide oligomers (NAIOs) obtained by thermally treating an in situ polymerization of monomeric reactant (PMR)-type poly(amide ester) resin solution. The PMR poly(amide ester) was synthesized by the reaction of diethyl ester of 2,3,3′,4′-biphenyltetracarboxylic dianhydride and aromatic diamines using monoethyl ester of cis-5-norbornene-endo-2,3-dicarboxylic acid as reactive end-capping agent in ethyl alcohol. The thermal foaming properties of the NAIOs were investigated. It was found that thermal foaming of the NAIOs was attributed to the blowing of cyclopentadiene, which was evolved from thermal decomposition of the nadimide end-caps in the imide oligomer by the reverse Diels–Alder reaction during cross-linking of the bisnadimide oligomers. The resultant rigid PIFs showed uniform cellular structures with high closed-cell content ( Cc) as well as high thermal stability and mechanical properties. The PIF with a density of 100 kg m−3 and a Cc of 89% exhibited compression strength at 10% compressive deformation of 1.34 MPa and outstanding thermal stabilities, making it a desirable candidate as high temperature structural foam materials for applications in aviation and spacecraft industries.
Herpes simplex virus type 2 incidence and associated risk factors among female sex workers in a high HIV-prevalence area of China
Authors: Wang H , Reilly K H , Smith M K , Brown K , Jin X , Xu J , Ding G , Zang C , Wang J , Wang N
Published: June 2013

Summary

Herpes simplex virus type 2 (HSV-2) can contribute to the spread of HIV. From March 2006 to November 2009, female sex workers (FSWs) in Yunnan, China were recruited into an open cohort study to determine incidence and risk factors for HSV-2 acquisition. Participants were interviewed and tested for HSV-2 and other sexually transmitted infections (STIs) every six months. A multivariate Cox proportional hazards regression model with time-dependent variables was used to measure associations with HSV-2 acquisition. In 3.5 years, 83 incident cases of HSV-2 infection were diagnosed, yielding an overall incidence of 21.9 per 100 person years (PY) (95% confidence interval [CI], 17.8–26.3). Working in higher risk commercial sex venues, current Neisseria gonorrhoeae infection, age of sexual debut <18 years and lack of a regular sex partner were independent factors associated with HSV-2 acquisition. The high incidence of HSV-2 suggests that prevention methods for HIV/STI control are urgently needed.
Women's preferences for testing and management of sexually transmitted infections among low-income New York City family planning clients
Authors: Jones H E , Holloway I W , Pressman E , Meier J , Westhoff C L
Published: June 2013

Summary

High prevalence of chlamydia in the USA persists despite efforts to annually screen women under the age of 26. Tailoring sexually transmitted infection (STI) services to client preferences may strengthen existing programmes. We report women's preferences for STI services from a family planning clinic in New York City serving low-income women. Seventy-eight percent (995/1275) of eligible women participated, with a mean age of 26 (SD±7). Ninety-one percent self-identified as Latina. Nineteen percent reported a past STI. Women preferred self-collection (65%) for testing to a speculum exam (20%); 15% had no preference. Women with a previous STI were more likely to prefer a pelvic exam to women with no previous STI (50% versus 32%, P < 0.01). Nearly all women (94%) preferred informing a sex partner about a positive STI test themselves, but 88% were willing to bring expedited partner therapy to a partner. Women were more likely to prefer third party partner notification if their last partner was casual rather than a main partner (14% versus 3%, respectively, P < 0.01). Forty-four percent of participants worried about physical violence after partner notification. Self-collecting specimens for screening was widely acceptable. Partner notification strategies should be based on understanding partnership status, including fears of violence.
Clinical practitioner’s attitudes towards the use of Routine Outcome Monitoring within Child and Adolescent Mental Health Services: A qualitative study of two Child and Adolescent Mental Health Services
Authors: Norman Shelley , Dean Sarah , Hansford Lorraine , Ford Tamsin
Published: June 2013

Routine Outcome Monitoring (ROM) is held as a greatly important part of practice across many Health Care Services, both in the NHS and in private practice. Yet despite this, there has been little research into the attitudes of practitioners towards ROM. This paper looks at the attitudes of 50 clinicians from two Child and Adolescent Mental Health Services in greater London. The findings showed that although the practitioners were not overwhelming positive in their attitudes to ROM, neither were they overwhelming negative, and many of their concerns involved practical issues surrounding ROM that are potentially soluble. Practitioner engagement in ROM is key if ROM is to be used constructively to reflect on practice.
Recent temporal trends in sleep duration, domain-specific sedentary behaviour and physical activity. A survey among 25–79-year-old Danish adults
Authors: Aadahl Mette , Andreasen Anne Helms , Hammer-Helmich Lene , Buhelt Lone , Jørgensen Torben , Glümer Charlotte
Published: June 2013

Background: Prevalence of sedentary behaviour is high in many countries, but little is known about temporal trends in sitting time. Objective: To examine temporal changes in sleep and domain-specific sedentary behaviour and moderate to vigorous leisure time physical activity (MVPA). Methods: Two cross-sectional population-based surveys of 25–79-year-old inhabitants were conducted in The Capital Region of Denmark in 2007 ( N = 69.800, response rate 52.3%) and 2010 ( N = 77.517, response rate 54.8%). Information on sedentary behaviour and physical activity was obtained from self-report questionnaire and sociodemographic information from central registers. Data were weighted for survey design and for non-response and were analysed by multiple regression analyses. Results: In 2007, the entire survey population reported a mean daily sleeping duration of 7.4 hours, leisure time sitting of 3.4 hours per day, occupational sitting of 4.4 hours per day, MVPA of 0.87 hours per day and a total 24-hour energy expenditure of 40.12 METs per day. In 2010, duration of sleep was unaltered ( p = 0.1), sedentary leisure time and sedentary work time had increased by 12.6 minutes ( p < 0.0001) and 13.2 minutes ( p < 0.0001) per day, respectively. Time spent on MVPA had increased by 2.9 minutes per day ( p < 0.0001). The 24-hour energy expenditure had decreased by 0.41 METs ( p < 0.0001). Conclusions: Adult Danish men and women spend an increased amount of time sitting down at work and during leisure time, but also on leisure time MVPA. As duration of sleep is unaltered findings suggest that low intensity physical activity may be displaced in everyday life.
Piezoelectric material selection for ultrasonic transducer and actuator applications
Authors: Chauhan Aditya , Vaish Rahul , Bowen Chris
Published: June 2013

Multi attribute decision making approaches are used to screen and rank selected materials for piezoelectric applications including ultrasonic transducers and actuators. We have investigated two separate multi attribute decision making techniques namely the technique for order preference by similarity to ideal solution and non-linear simple additive weighting methods to rank and compare selected materials for high and room temperature piezoelectric applications. Subjective weights have been determined using modified digital logic approach. Lead-based piezoceramics acquire all the top ranking positions, indicating their functional superiority among all the selected materials. However, some lead-free materials show comparable performance index with that of the lead-based ceramics. The KNN (K0.5Na0.5NbO3) family in particular shows positive simple additive weighting index, indicating potential lead-free candidates for piezoelectric applications.
Impact of gasoline composition on particulate matter emissions from a direct-injection gasoline engine: Applicability of the particulate matter index
Authors: Aikawa Koichiro , Jetter Jeff J
Published: June 2013

The new fuel property “particulate matter (PM) index” suggested by Aikawa et al. in their previous report, which reflects particulate matter emission potential of gasoline, has been shown to have a significant correlation with PM in port fuel injection engine. However, the particulate matter index applicability to direct-injection gasoline engines has not been well verified. The purpose of this study is to confirm the particulate matter index applicability to direct-injection gasoline engines. Results verified good correlation between particulate matter index and particulate matter emissions of a direct-injection gasoline engine, just as with the port fuel injection engine. The verification of particulate number emissions of the direct-injection gasoline engine on the US FTP-75 cycle indicated a high correlation with the particulate matter index. In particular, a significantly high correlation (R2 = 0.9644) was observed in the FTP-75 cold-start phase (Phase 1) in which the fuel influences are considered most evident. The filter PM (PM mass) was simultaneously measured, and its correlation with PM index was verified. The correlation with PM mass was slightly lower than with particulate number, but it also had a good correlation with PM index. This indicated that the PM index will apply well to DI gasoline engines.
Cylinder-to-cylinder variation sources in diesel low temperature combustion and the influence they have on emissions
Authors: Bittle Joshua , Zheng Junnian , Xue Xingyu , Song Hoseok , Jacobs Timothy
Published: June 2013

Cylinder-to-cylinder variation in a multi-cylinder diesel engine was found to increase substantially when transitioning to a low-temperature combustion mode. This study was started to investigate the potential influence this effect could have on the emissions levels. Initial testing showed an imbalance in the fuel distribution that prompted this article to focus on data from before and after swapping two injectors under both conventional and low-temperature combustion modes. A significant improvement is observed in cylinder variation based both on visual heat release inspection and on mean effective pressure variation. This is likely a result of a changing combination of exhaust gas recirculation and fuel distribution such that less cylinder-to-cylinder variation is present (e.g. high dilution and low fuel, switched to low dilution and low fuel).

Interestingly, despite the reduced cylinder-to-cylinder variation, the results show that the emissions levels are actually not affected. Despite the lack of influence on emissions results, the cylinder-to-cylinder variation in low-temperature combustion modes is still a critical factor that could impact its ability to be implemented in a commercial setting. Further cylinder balancing was attempted and achieved by introducing small (microsecond) adjustments to each cylinder start of injection and injection duration. The balancing is effective, but due to exhaust gas recirculation imbalance, a single adjustment setting does not apply to both conventional and low-temperature combustion modes. Additionally, day-to-day ambient conditions also negate the effectiveness. This supports the idea that some type of consumer-based real-time automatic balancing system may be needed in the future.
Dimming properties of medium and small wattage ceramic metal halide lamps
Authors: Li W , Shi SJ , Liu J , Lister G , Zhang SD
Published: June 2013

Ceramic metal halide lamps with rated powers of 70 W and 150 W are dimmed by reducing their operating power. Under dimmed conditions, photometric, colorimetric and electric parameters, as well as the temperature distribution of the outer wall of the arc tube have been measured. As the lamp power is reduced, luminous efficacy and colour rendering index decrease while correlated colour temperature rises. For each lamp, at 70% of its rated power, the luminous efficacy is greater than 80 lm/W, colour rendering index is above 74 and correlated colour temperature increases by less than 800 K. Dimming applications of these lamps are validated by these parameters. Furthermore, the complicated variation of lamp parameters as a function of operating power is explained by the variation of metal halide vapour pressure with wall temperature.
Angiotensin II regulates collagen metabolism through modulating tissue inhibitor of metalloproteinase-1 in diabetic skin tissues
Authors: Ren Meng , Hao Shaoyun , Yang Chuan , Zhu Ping , Chen Lihong , Lin Diaozhu , Li Na , Yan Li
Published: June 2013

We investigated the effect of angiotensin II (Ang II) on matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) balance in regulating collagen metabolism of diabetic skin. Skin tissues from diabetic model were collected, and the primary cultured fibroblasts were treated with Ang II receptor inhibitors before Ang II treatment. The collagen type I (Coll I) and collagen type III (Coll III) were measured by histochemistry. The expressions of transforming growth factor-β (TGF-β), MMP-1, TIMP-1 and propeptides of types I and III procollagens in skin tissues and fibroblasts were quantified using polymerase chain reaction (PCR), Western blot or enzyme-linked immunosorbent assay (ELISA). Collagen dysfunction was documented by changed collagen I/III ratio in streptozotocin (STZ)-injected mice compared with controls. This was accompanied by increased expression of TGF-β, TIMP-1 and propeptides of types I and III procollagens in diabetic skin tissues. In primary cultured fibroblasts, Ang II prompted collagen synthesis accompanied by increases in the expressions of TGF-β, TIMP-1 and types I and III procollagens, and these increases were inhibited by losartan, an Ang II type 1 (AT1) receptor blocker, but not affected by PD123319, an Ang II type 2 (AT2) receptor antagonist. These findings present evidence that Ang-II-mediated changes in the productions of MMP-1 and TIMP-1 occur via AT1 receptors and a TGF-β-dependent mechanism.
Causes of recurrent lower limb varicose veins after surgical interventions in 141 limbs – Five-year retrospective analysis of two centers
Authors: Hua Wang Rui , Yi Meng Qing , Jun Wu Xue , Xing Jin , Xuan Liu Zhao , Bo Li
Published: June 2013

Aim

The purpose of this study was to explore the causes of recurrent lower limb varicose veins after surgical interventions.

Methods

A retrospective five-year survey was conducted on patients who underwent second surgery due to recurrent lower limb varicose veins after surgical interventions. A total of 141 limbs (112 cases), including 72 cases of left lower limbs, 47 of right lower limbs and 22 of both limbs, were involved in the study. All patients underwent lower limb venography (141 limbs were anterograde and 28 cases were retrograde), and then examined with color-Doppler ultrasound.

Results

The major causes that urged patients to undergo second surgery are clinical changes graded above CEAP IV (93.6%), limb edema without changes on skin (5%), and single varicosity (1.4%). Up to 127 (83%) limbs exhibited perforating venous reflux, 67 (47.5%) limbs had varied degrees of deep venous insufficiency and 68 (48.2%) limbs had through or above-the-knee great saphenous vein trunk residual.

Conclusions

Preoperative venography before operation is indispensible in confirming the diagnosis and operation strategies. Patients with severe primary deep venous reflux and symptoms up to C3 may need simultaneous repair of the deep venous valves.
Pornographic Protections? Itineraries of Childhood Innocence
Authors: Fischel Joseph J.
Published: June 2013

Legal and queer theoretic critics charge that the myth of “childhood innocence” perverts and propagates the unwarranted expansion of child pornography law, and mischaracterizes sources of and solutions to sexual violence. This article spells out these criticisms and synthesizes them with recent scholarship on the racialization of innocence. In thinking these literatures together, we are able to survey the complexities of “innocence” as a political idiom for the promotion of social and sexual welfare. I conclude with the reminder that no idiom – whether “innocence,” “harm,” or “agency” – is purified of normative judgment.
Factors affecting satisfaction with treatment in European women with chronic constipation: An internet survey
Authors: Emmanuel Anton , Quigley Eamonn MM , Simrén Magnus , Feng Yue , Müller‐Lissner Stefan , Urbain Daniel , Tack Jan , Bredenoord Albert J , Sabaté Jean‐Marc , Yiannakou Yan , Andresen Viola , Cuomo Rosario , Rey Enrique , Gryp Renate Specht , Vandeplassche Lieve , Solomon Dory
Published: June 2013

Background

Data on factors affecting treatment satisfaction in European women with chronic constipation are limited.

Objective

To assess factors associated with treatment satisfaction among European women with chronic constipation.

Methods

A 2011–2012 internet survey was conducted in men and women from 12 European countries. Respondents analysed were female with self‐reported chronic constipation (≥1 symptoms for ≥6 months of lumpy/hard stools, feeling of incomplete evacuation, and pain during defecation, as well as <3 bowel movements/week). For laxative users, satisfaction with treatment, factors affecting satisfaction, and interactions with healthcare professionals were collected.

Results and conclusions

In total, 4805/50,319 participants fulfilled the inclusion criteria (female with chronic constipation). Of the laxative users (1575/4805), 57% (n  = 896) were satisfied with their treatment, while 26% were neutral, and 17% dissatisfied. Dissatisfied respondents visited their GP less frequently in the past 12 months, were more likely to obtain over‐the‐counter laxatives, and took a dose higher than recommended more frequently than those satisfied. Respondents were most satisfied with ease of use of treatment and least satisfied with relief from bloating. Newer treatments aimed at alleviating symptoms, particularly bloating, are required for respondents neutral or dissatisfied with their current treatment.
Application of international consensus diagnostic criteria to an Italian series of autoimmune pancreatitis
Authors: Ikeura Tsukasa , Manfredi Riccardo , Zamboni Giuseppe , Negrelli Riccardo , Capelli Paola , Amodio Antonio , Caliò Anna , Colletta Giulia , Gabbrielli Armando , Benini Luigi , Okazaki Kazuichi , Vantini Italo , Frulloni Luca
Published: June 2013

Background

International consensus diagnostic criteria (ICDC) have been proposed to classify autoimmune pancreatitis (AIP) in type 1, type 2, or not otherwise specified.

Objective

Aim was to apply the ICDC to an Italian series of patients to evaluate the incidence and clinical profiles among different subtypes of AIP.

Methods

we re‐evaluated and classified 92 patients diagnosed by Verona criteria, according to the ICDC.

Results

Out of 92 patients, 59 (64%) were diagnosed as type 1, 17 (18%) as type 2, and 15 (16%) as not otherwise specified according to the ICDC. A significant difference between type 1 and type 2 were found for age (54.5 ± 14.5 vs. 34.4 ± 13.9 respectively; p  < 0.0001), male sex (76 vs. 47%; p  = 0.007), jaundice (66 vs. 18%; p  = 0.002) and acute pancreatitis (9 vs. 47%; p  < 0.0001), elevated serum IgG4 levels (85 vs. 7%; p  < 0.0001), inflammatory bowel disease (8 vs. 82%; < 0.0001), and relapse of the disease (34 vs. 6%; p  = 0.058). Imaging and response to steroids in the not‐otherwise‐specified group were similar to type 1 and 2.

Conclusions

Type 1 has a different clinical profile from type 2 autoimmune pancreatitis. The not‐otherwise‐specified group has peculiar clinical features which are shared both with type 1 or type 2 groups.
Tumor-derived tissue factor–positive microparticles and venous thrombosis in cancer patients
Authors: Geddings Julia E. , Mackman Nigel
Published: June 2013

Patients with cancer have an increased risk for venous thrombosis. Interestingly, different cancer types have different rates of thrombosis, with pancreatic cancer having one of the highest rates. However, the mechanisms responsible for the increase in venous thrombosis in patients with cancer are not understood. Tissue factor (TF) is a transmembrane receptor and primary initiator of blood coagulation. Tumor cells express TF and spontaneously release TF-positive microparticles (MPs) into the blood. MPs are small membrane vesicles that are highly procoagulant. It has been proposed that these circulating tumor-derived, TF-positive MPs may explain the increased rates of venous thrombosis seen in patients with cancer. In animal models, increased levels of tumor-derived, TF-positive MPs are associated with activation of coagulation. Moreover, these MPs bind to sites of vascular injury and enhance thrombosis. We and others have found that patients with cancer have elevated levels of circulating TF-positive MPs. These MPs are derived from tumors because they express tumor markers and are decreased by tumor resection. Importantly, several studies have shown that increased levels of TF-positive MPs correlate with venous thrombosis in patients with cancer. Taken together, these results suggest that TF-positive MPs may be a useful biomarker to identify patients with cancer who are at high risk for thrombosis.
An emerging role for the anti-inflammatory cytokine interleukin-10 in dengue virus infection
Authors: Tsai Tsung-Ting , Chuang Yi-Jui , Lin Yee-Shin , Wan Shu-Wen , Chen Chia-Ling , Lin Chiou-Feng
Published: June 2013

Infection with dengue virus (DENV) causes both mild dengue fever and severe dengue diseases, such as dengue hemorrhagic fever and dengue shock syndrome. The pathogenic mechanisms for DENV are complicated, involving viral cytotoxicity, immunopathogenesis, autoimmunity, and underlying host diseases. Viral load correlates with disease severity, while the antibody-dependent enhancement of infection largely determines the secondary effects of DENV infection. Epidemiological and experimental studies have revealed an association between the plasma levels of interleukin (IL)-10, which is the master anti-inflammatory cytokine, and disease severity in patients with DENV infection. Based on current knowledge of IL-10-mediated immune regulation during infection, researchers speculate an emerging role for IL-10 in clinical disease prognosis and dengue pathogenesis. However, the regulation of dengue pathogenesis has not been fully elucidated. This review article discusses the regulation and implications of IL-10 in DENV infection. For future strategies against DENV infection, manipulating IL-10 may be an effective antiviral treatment in addition to the development of a safe dengue vaccine.
Involvement of STIM1 and Orai1 in EGF-mediated cell growth in retinal pigment epithelial cells
Authors: Yang I-Hui , Tsai Yao-Ting , Chiu Siou-Jin , Liu Li-Teh , Lee Hsuan-Hung , Hou Ming-Feng , Hsu Wen-Li , Chen Ben-Kuen , Chang Wei-Chiao
Published: June 2013

Background

In non-excitable cells, one major route for calcium entry is through store-operated calcium (SOC) channels in the plasma membrane. These channels are activated by the emptying of intracellular Ca2+ store. STIM1 and Orai1 are major regulators of SOC channels. In this study, we explored the functions of STIM1 and Orai1 in epidermal growth factor (EGF)-induced cell proliferation and migration in retinal pigment epithelial cells (ARPE-19 cell line).

Results

EGF triggers cell proliferation and migration in ARPE-19 cells. Cell proliferation and migration involve STIM1 and Orai1, as well as phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2, and Akt. Pharmacological inhibitors of SOC channels and siRNA of Orai1 and STIM1 suppress cell proliferation and migration. Pre-treatment of mitogen-activated protein kinase kinase (MEK) inhibitors and a phosphatidylinositol 3 kinases (PI3K) inhibitor attenuated cell proliferation and migration. However, inhibition of the SOC channels failed to prevent EGF-mediated ERK 1/2 and Akt phosphorylation.

Conclusions

Our results showed that STIM1, Orai1, ERK 1/2, and Akt are key determinants of EGF-mediated cell growth in ARPE-19 cells. EGF is a potent growth molecule that has been linked to the development of PVR, and therefore, STIM1, Orai1, as well as the MEK/ERK 1/2 and PI3K/Akt pathways, might be potential therapeutic targets for drugs aimed at treating such disorders.
Impaired proteasomal degradation enhances autophagy via hypoxia signaling in Drosophila
Authors: Lőw Péter , Varga Ágnes , Pircs Karolina , Nagy Péter , Szatmári Zsuzsanna , Sass Miklós , Juhász Gábor
Published: June 2013

Background

Two pathways are responsible for the majority of regulated protein catabolism in eukaryotic cells: the ubiquitin-proteasome system (UPS) and lysosomal self-degradation through autophagy. Both processes are necessary for cellular homeostasis by ensuring continuous turnover and quality control of most intracellular proteins. Recent studies established that both UPS and autophagy are capable of selectively eliminating ubiquitinated proteins and that autophagy may partially compensate for the lack of proteasomal degradation, but the molecular links between these pathways are poorly characterized.

Results

Here we show that autophagy is enhanced by the silencing of genes encoding various proteasome subunits (α, β or regulatory) in larval fat body cells. Proteasome inactivation induces canonical autophagy, as it depends on core autophagy genes Atg1, Vps34, Atg9, Atg4 and Atg12. Large-scale accumulation of aggregates containing p62 and ubiquitinated proteins is observed in proteasome RNAi cells. Importantly, overexpressed Atg8a reporters are captured into the cytoplasmic aggregates, but these do not represent autophagosomes. Loss of p62 does not block autophagy upregulation upon proteasome impairment, suggesting that compensatory autophagy is not simply due to the buildup of excess cargo. One of the best characterized substrates of UPS is the α subunit of hypoxia-inducible transcription factor 1 (HIF-1α), which is continuously degraded by the proteasome during normoxic conditions. Hypoxia is a known trigger of autophagy in mammalian cells, and we show that genetic activation of hypoxia signaling also induces autophagy in Drosophila. Moreover, we find that proteasome inactivation-induced autophagy requires sima, the Drosophila ortholog of HIF-1α.

Conclusions

We have characterized proteasome inactivation- and hypoxia signaling-induced autophagy in the commonly used larval Drosophila fat body model. Activation of both autophagy and hypoxia signaling was implicated in various cancers, and mutations affecting genes encoding UPS enzymes have recently been suggested to cause renal cancer. Our studies identify a novel genetic link that may play an important role in that context, as HIF-1α/sima may contribute to upregulation of autophagy by impaired proteasomal activity.
Genetic variation in four maturity genes affects photoperiod insensitivity and PHYA-regulated post-flowering responses of soybean
Authors: Xu Meilan , Xu Zeheng , Liu Baohui , Kong Fanjiang , Tsubokura Yasutaka , Watanabe Satoshi , Xia Zhengjun , Harada Kyuya , Kanazawa Akira , Yamada Testuya , Abe Jun
Published: June 2013

Background

Absence of or low sensitivity to photoperiod is necessary for short-day crops, such as rice and soybean, to adapt to high latitudes. Photoperiod insensitivity in soybeans is controlled by two genetic systems and involves three important maturity genes: E1, a repressor for two soybean orthologs of Arabidopsis FLOWERING LOCUS T (GmFT2a and GmFT5a), and E3 and E4, which are phytochrome A genes. To elucidate the diverse mechanisms underlying photoperiod insensitivity in soybean, we assessed the genotypes of four maturity genes (E1 through E4) in early-flowering photoperiod-insensitive cultivars and their association with post-flowering responses.

Results

We found two novel dysfunctional alleles in accessions originally considered to have a dominant E3 allele according to known DNA markers. The E3 locus, together with E1 and E4, contained multiple dysfunctional alleles. We identified 15 multi-locus genotypes, which we subdivided into 6 genotypic groups by classifying their alleles by function. Of these, the e1-as/e3/E4 genotypic group required an additional novel gene (different from E1, E3, and E4) to condition photoperiod insensitivity. Despite their common pre-flowering photoperiod insensitivity, accessions with different multi-locus genotypes responded differently to the post-flowering photoperiod. Cultivars carrying E3 or E4 were sensitive to photoperiod for post-flowering characteristics, such as reproductive period and stem growth after flowering. The phytochrome A–regulated expression of the determinate growth habit gene Dt1, an ortholog of Arabidopsis TERMINAL FLOWER1, was involved in the persistence of the vegetative activity at the stem apical meristem of flower-induced plants under long-day conditions.

Conclusions

Diverse genetic mechanisms underlie photoperiod insensitivity in soybean. At least three multi-locus genotypes consisting of various allelic combinations at E1, E3, and E4 conferred pre-flowering photoperiod insensitivity to soybean cultivars but led to different responses to photoperiod during post-flowering vegetative and reproductive development. The phyA genes E3 and E4 are major controllers underlying not only pre-flowering but also post-flowering photoperiod responses. The current findings improve our understanding of genetic diversity in pre-flowering photoperiod insensitivity and mechanisms of post-flowering photoperiod responses in soybean.
In-plane optical anisotropy of InAs/GaSb superlattices with alternate interfaces
Authors: Wu Shujie , Chen Yonghai , Yu Jinling , Gao Hansong , Jiang Chongyun , Huang Jianliang , Zhang Yanhua , Wei Yang , Ma Wenquan
Published: June 2013

The in-plane optical anisotropy (IPOA) in InAs/GaSb superlattices has been studied by reflectance difference spectroscopy (RDS) at different temperatures ranging from 80 to 300 K. We introduce alternate GaAs- and InSb-like interfaces (IFs), which cause the symmetry reduced from D
2d
to C
2v
. IPOA has been observed in the (001) plane along [110] and [1

1

¯

0] axes. RDS measurement results show strong anisotropy resonance near critical point (CP) energies of InAs and GaSb. The energy positions show red shift and RDS intensity decreases with the increasing temperature. For the superlattice sample with the thicker InSb-like IFs, energy positions show red shift, and the spectra exhibit stronger IPOA. The excitonic effect is clearly observed by RDS at low temperatures. It demonstrates that biaxial strain results in the shift of the CP energies and IPOA is enhanced by the further localization of the carriers in InSb-like IFs.

PACS

78.67.Pt, 78.66.Fd, 78.40.Fy
Assessing the effectiveness and cost effectiveness of subcutaneous nerve stimulation in patients with predominant back pain due to failed back surgery syndrome (SubQStim study): study protocol for a multicenter randomized controlled trial
Authors: Eldabe Sam , Kern Michael , Peul Wilco , Green Colin , Winterfeldt Kristi , Taylor Rod S
Published: June 2013

Background

Chronic radicular pain can be effectively treated with spinal cord stimulation, but this therapy is not always sufficient for chronic back pain. Subcutaneous nerve stimulation (SQS) refers to the placement of percutaneous leads in the subcutaneous tissue within the area of pain. Case series data show that failed back surgery syndrome (FBSS) patients experience clinically important levels of pain relief following SQS and may also reduce their levels of analgesic therapy and experience functional well-being. However, to date, there is no randomized controlled trial evidence to support the use of SQS in FBSS.

Methods/Design

The SubQStim study is a multicenter randomized controlled trial comparing SQS plus optimized medical management (‘SQS arm’) versus optimized medical management alone (‘OMM arm’) in patients with predominant back pain due to FBSS. Up to 400 patients will be recruited from approximately 33 centers in Europe and Australia and will be randomized 1:1 to the SQS or OMM arms. After 9 months, patients who fail to reach the primary outcome will be allowed to switch treatments. Patients will be evaluated at baseline (prior to randomization) and at 1, 3, 6, 9, 12, 18, 24, and 36 months after randomization. The primary outcome is the proportion of patients at 9 months with a ≥50% reduction in back pain intensity compared to baseline. The secondary outcomes are: back and leg pain intensity score, functional disability, health-related quality of life, patient satisfaction, patient global impression of change, healthcare resource utilization/costs, cost-effectiveness analysis and adverse events. Outcomes arms will be compared between SQS and OMM arms at all evaluation points up to and including 9 months. After the 9-month assessment visit, the main analytic focus will be to compare within patient changes in outcomes relative to baseline.

Discussion

The SubQStim trial began patient recruitment in November 2012. Recruitment is expected to close in late 2014.

Trial registration

ClinicalTrials.gov NCT01711619
Sharpening of expression domains induced by transcription and microRNA regulationwithin a spatio-temporal model of mid-hindbrain boundary formation
Authors: Hock Sabrina , Ng Yen-Kar , Hasenauer Jan , Wittmann Dominik , Lutter Dominik , Trümbach Dietrich , Wurst Wolfgang , Prakash Nilima , Theis Fabian J
Published: June 2013

Background

The establishment of the mid-hindbrain region in vertebrates is mediated by theisthmic organizer, an embryonic secondary organizer characterized by awell-defined pattern of locally restricted gene expression domains with sharplydelimited boundaries. While the function of the isthmic organizer at themid-hindbrain boundary has been subject to extensive experimental studies, itremains unclear how this well-defined spatial gene expression pattern, which isessential for proper isthmic organizer function, is established during vertebratedevelopment. Because the secreted Wnt1 protein plays a prominent role in isthmicorganizer function, we focused in particular on the refinement of Wnt1gene expression in this context.

Results

We analyzed the dynamics of the corresponding murine gene regulatory network andthe related, diffusive signaling proteins using a macroscopic model for thebiological two-scale signaling process. Despite the discontinuity arisingfrom the sharp gene expression domain boundaries, we proved the existence ofunique, positive solutions for the partial differential equation system. Thisenabled the numerically and analytically analysis of the formation and stabilityof the expression pattern. Notably, the calculated expression domain ofWnt1 has no sharp boundary in contrast to experimental evidence. Wesubsequently propose a post-transcriptional regulatory mechanism for Wnt1miRNAs which yields the observed sharp expression domain boundaries. Weestablished a list of candidate miRNAs and confirmed their expression pattern byradioactive in situ hybridization. The miRNA miR-709 was identified as apotential regulator of Wnt1 mRNA, which was validated by luciferasesensor assays.

Conclusion

In summary, our theoretical analysis of the gene expression pattern induction atthe mid-hindbrain boundary revealed the need to extend the model by an additionalWnt1 regulation. The developed macroscopic model of a two-scaleprocess facilitate the stringent analysis of other morphogen-based patterningprocesses.