Miracle-dz/UniFAR-FTUs huggingface dataset:
Antinociceptive property of tegaserod in a rat model of chronic visceral hypersensitivity.

OBJECTIVE To establish a model of chronic visceral hypersensitivity in rats and to investigate the effect of tegaserod, a partial 5-hydroxytryptamine-4 receptor agonist, on visceral hypersensitivity. METHODS Neonate Sprague-Dawley rats at 8-21 days after birth underwent colorectal distension once daily. Adult rats aged 8-10 postnatal weeks underwent colorectal distension and the abdominal withdrawal reflex (AWR) during the distension was determined. The AWR score was recorded before and after intraperitoneal administration of either tegaserod (treatment group: 0.3 mg/kg) or vehicle (control group). RESULTS Changes in the AWR score were dependent on the pressure intensity of the colorectal distension (P < 0.01). At pressures of 40, 60 and 80 mmHg, the AWR scores in the model rats with visceral hypersensitivity were significantly higher than those recorded in the control group (1.95 +/- 0.16 vs 1.35 +/- 0.15, 2.82 +/- 0.12 vs 2.17 +/- 0.13, 3.20 +/- 0.14 vs 2.59 +/- 0.14, P < 0.01). Compared with the controls, tegaserod significantly decreased the AWR scores at the distension pressures of 40, 60 and 80 mmHg (1.95 +/- 0.50 vs 1.32 +/- 0.55, 3.05 +/- 0.48 vs 2.32 +/- 0.54, 3.25 +/- 0.63 vs 2.77 +/- 0.51, P < 0.05). CONCLUSIONS Adult rats can develop chronic visceral hypersensitivity after transient colorectal mechanical irritation during their postnatal period. Tegaserod increases the pain threshold to noxious stimuli, suggesting an antinociceptive property in its effect on visceral hypersensitivity.
Development and Dosimetry of a Small Animal Lung Irradiation Platform

Abstract Advances in large scale screening of medical countermeasures for radiation-induced normal tissue toxicity are currently hampered by animal irradiation paradigms that are both inefficient and highly variable among institutions. Here, a novel high-throughput small animal irradiation platform is introduced for use in orthovoltage small animal irradiators. Radiochromic film and metal oxide semiconductor field effect transistor detectors were used to examine several parameters, including 2D field uniformity, dose rate consistency, and shielding transmission. The authors posit that this setup will improve efficiency of drug screens by allowing for simultaneous targeted irradiation of multiple animals to improve efficiency within a single institution. Additionally, they suggest that measurement of the described parameters in all centers conducting countermeasure studies will improve the translatability of findings among institutions. The use of tissue equivalent phantoms in performing dosimetry measurements for small animal irradiation experiments was also investigated. Though these phantoms are commonly used in dosimetry, the authors recorded a significant difference in both the entrance and target tissue dose rates between euthanized rats and mice with implanted detectors and the corresponding phantom measurement. This suggests that measurements using these phantoms may not provide accurate dosimetry for in vivo experiments. Based on these measurements, the authors propose that this small animal irradiation platform can increase the capacity of animal studies by allowing for more efficient animal irradiation. They also suggest that researchers fully characterize the parameters of whatever radiation setup is in use in order to facilitate better comparison among institutions.
The potential impact of primary percutaneous coronary intervention on ventricular septal rupture complicating acute myocardial infarction.

BACKGROUND Recent data suggest that the risk of acquired ventricular septal defect (VSD), a complication of acute myocardial infarction (AMI), could be reduced using thrombolytic therapy. There are, however, still no available data regarding the potential impact of primary percutaneous coronary intervention (PCI) on AMI-related VSD in a clinical setting. The purposes of this study were to delineate the incidence and the potential risk factors of AMI-related VSD in the Chinese population, and to determine whether primary PCI could reduce such risk. METHODS AND RESULTS From May 1993 through March 2003, a total of 1,321 patients with AMI (for < 12 h) underwent primary PCI in our hospital. Of these 1,321 patients, 3 patients (0.23%) developed VSD after undergoing a primary PCI, with a mean (+/- SD) time of occurrence of 25.3 +/- 12.2 h. During the same period, a total of 616 consecutive, unselected patients with early AMI [ie, > 12 h and < or = 7 days] or recent myocardial infarction (MI) [ie, > or = 8 days and < 30 days] who had not received thrombolytic therapy underwent elective PCI. Of these 616 patients, 18 (2.9%) had VSD either on presentation or during hospitalization, with a mean time of occurrence of 71.1 +/- 64.2 h. Clinical variables were utilized to statistically analyze the potential risk factors. Univariate analysis demonstrated that the enrollment variables strongly related to this complication were advanced age, hypertension, nonsmokers, anterior infarction, female gender, and lower body mass index (BMI) [all p < 0.005]. Using multiple stepwise logistic regression analysis, the only variables independently related to VSD were advanced age, female gender, anterior infarction, and low BMI (all p < 0.05). The in-hospital mortality rate was significantly higher in patients with this complication than in patients without this complication (47.6% vs 8.0%; p < 0.0001). The incidence of this complication was significantly lower in patients with AMI who underwent primary PCI than in those with early or recent MI who underwent elective PCI (3.0% vs 0.23%, respectively; p = 0.0001). CONCLUSION Primary PCI had a striking impact on reducing the incidence of VSD after AMI compared to elective PCI in patients who did not receive thrombolytic therapy. Advanced age, female gender, anterior infarction, and low BMI had potentially increased the risk of this catastrophic complication after AMI in this Chinese population.
[Study of C807T polymorphism of the platelet collagen receptor alpha2 gene coding sequence in Suzhou Han population].

OBJECTIVE To study the C807T polymorphism of the platelet collagen receptor alpha(2) gene coding sequence in Suzhou Han population. This polymorphism was associated with the expression density of integrin alpha(2)beta(1) on the platelet surface. METHODS An amplified 1332 bp fragment of human alpha(2) gene from 110 unrelated individuals was analyzed by Bgl II and Ase I restriction assay. The resulting products were electrophoresed in 8% polyacrylamide gels and stained with ethidium bromide. RESULTS The allelic frequencies were 0.291:0.709 for T807 allele: C807 allele in Suzhou Han population. The total theoretical heterozygous rate was 41%. The genotypic frequencies were 0.018:0.546:0.436 for homozygous 807T allele: heterozygous 807C/T allele: homozygous 807C allele. CONCLUSION The C807T polymorphism of the platelet collagen receptor alpha2 gene in Suzhou Han population was different from that observed in other populations.
The natural history of inflammatory bowel disease and primary sclerosing cholangitis after liver transplantation--a single-centre experience.

OBJECTIVE To describe the natural history of primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) after liver transplant, the predictors of PSC and IBD recurrence, and the interaction of these disease processes. METHODS Data regarding patients who received liver transplants for PSC at the University of Alberta Hospital (Edmonton, Alberta) from 1989 to 2006 were retrospectively reviewed. Recurrent PSC (rPSC) was defined by the Mayo Clinic criteria. Cox proportional hazards modelling and Kaplan-Meier statistics were used. RESULTS Fifty-nine patients were studied, with a median follow-up of 68 months. A total of 71.2% of patients were diagnosed with IBD pretransplant. Clinical IBD severity post-transplant compared with severity pretransplant was unchanged in 67%, worse in 26.5% and improved in 6.1% of patients. Twenty-five per cent of patients developed rPSC posttransplant. The occurrence of at least one episode of acute cellular rejection (hazard ratio 5.7; 95% CI 1.3 to 25.8) and cytomegalovirus mismatch (hazard ratio 4.2; 95% CI 1.1 to 15.4) were found to be significant predictors of rPSC. Although not statistically significant, there was no rPSC in patients without pre- or post-transplant IBD, and in only one patient with a colectomy. Actuarial patient survival rates at one, five and 10 years posttransplant were 97%, 86% and 79%, respectively. Although a significant proportion of patients experienced worsening IBD post-transplantation, the presence or severity of IBD did not influence rPSC or patient survival. CONCLUSION Acute cellular rejection and cytomegalovirus mismatch were both identified as independent predictors of rPSC. The impact of steroids and the ideal immunosuppressive regimen for the control of both IBD and PSC post-transplant requires further examination in prospective studies.
EARLY TERMINATION COMPENSATION UNDER DEMAND UNCERTAINTY IN PUBLIC-PRIVATE PARTNERSHIP PROJECTS

In the early termination of public-private partnership (PPP) projects, compensation is considered a core issue that greatly affects the interests of the government and the private sector. To address the early termination that is frequently caused by government default or voluntary buyback, this paper proposes an ex-ante compensation mechanism using the cumulative probability that a given demand could be realized to determine early termination compensation under demand uncertainty. By splitting the compensation into two parts, the base compensation could be the minimum compensation for the private sector, while the additional compensation is considered a reasonable allocation of future booming demand. The predetermined compensation criterion ensures a smooth transfer of the early terminated project, which not only benefits the government from being overcharged, but also enables the private sector to gain a reasonable compensation for the remaining concession period.
Increased expression of alpha 1-anti-trypsin in the synovial tissues of patients with ankylosing spondylitis.

OBJECTIVES Evidence indicates that the hyperplasia and inflammation of synovial tissues are significantly related to the pathogenic process of ankylosing spondylitis (AS). Using a proteomics approach, we detected a significantly increased expression of alpha 1-anti-trypsin (ATA1) in synovial membranes of patients with AS. METHODS We continued to investigate the expression level and location of ATA1 in synovial tissue of AS. We also investigated the genetic effect of the gene encoding ATA1 on AS. Western blot analysis was applied to determine the expression of ATA1 in synovial tissues by comparing the expression profiles of AS (n=8), rheumatoid arthritis (RA, n=9) and osteoarthritis (OA, n=9) samples. Immunohistochemistry was used to localise the expression of ATA1 in the synovial membrane. Taqman method was used to genotype tag SNPs (rs2753934, rs2749531 and rs6575424) with 56 AS cases, 260 RA cases and 160 healthy controls. RESULTS We detected an increased expression of ATA1 in synovial membranes of AS as compared with samples from RA and OA. We immuno-localised the significant expression of ATA1 in AS tissues. No significant association was found between the ATA1 polymorphism and AS or RA. Haplotype analysis did not reveal a haplotype to be associated with AS or RA. CONCLUSIONS It has been reported that ATA1 is related with inflammation and new bone formation, two important features of AS. The current findings suggest that ATA1 contributes to the pathogenesis of AS by up-regulating the gene expression in the synovial tissues.
A Novel Spore Protein, ExsM, Regulates Formation of the Exosporium in Bacillus cereus and Bacillus anthracis and Affects Spore Size and Shape

ABSTRACT Bacillus cereus spores are assembled with a series of concentric layers that protect them from a wide range of environmental stresses. The outermost layer, or exosporium, is a bag-like structure that interacts with the environment and is composed of more than 20 proteins and glycoproteins. Here, we identified a new spore protein, ExsM, from a β-mercaptoethanol extract of B. cereus ATCC 4342 spores. Subcellular localization of an ExsM-green fluorescent protein (GFP) protein revealed a dynamic pattern of fluorescence that follows the site of formation of the exosporium around the forespore. Under scanning electron microscopy, exsM null mutant spores were smaller and rounder than wild-type spores, which had an extended exosporium (spore length for the wt, 2.40 ± 0.56 μm, versus that for the exsM mutant, 1.66 ± 0.38 μm [P < 0.001]). Thin-section electron microscopy revealed that exsM mutant spores were encased by a double-layer exosporium, both layers of which were composed of a basal layer and a hair-like nap. Mutant exsM spores were more resistant to lysozyme treatment and germinated with higher efficiency than wild-type spores, and they had a delay in outgrowth. Insertional mutagenesis of exsM in Bacillus anthracis ΔSterne resulted in a partial second exosporium and in smaller spores. In all, these findings suggest that ExsM plays a critical role in the formation of the exosporium.
The Distribution of Mean Willingness to Pay in Mixed Logit Models: Classical, Bayesian and Resampling Approaches

Representation of the distribution of Willingness to Pay (WTP) in mixed logit models has been debated given the non-zero probability of a zero-denominator in the ratio of two normal random coefficients. This paper advocates focusing on the distribution of mean WTP and introduces three methods to reveal its distribution: the classical Delta method, the Bayesian approach with individual-level WTP, and a resampling method with the block delete jackknife. The empirical results first show the limitation of Delta method, reveals the skewness caused by applying a lognormal distribution on the price coefficient, and validates the virtues of the block delete jackknife and the Bayesian individual-level approach in describing the distribution of mean WTP.
The European Crisis: Repercussions on the Portuguese Economy

The recent economic and sovereign debt crisis strongly affected several European countries. This paper examines the implications on the Portuguese economy by exploring the effects of the crisis on the most relevant macroeconomic variables. We analyse the overall economic context in Portugal from the time it joined the euro until its bailout from Troika to understand the several factors that justify the need for the Economic and Financial Assistance Programme. Additionally, we investigate the repercussions of the crisis from 2008 onward, emphasizing the effects after 2011 that already include the impact of the austerity measures. Finally, we carry out an analysis of the projections in the medium term and we assess the challenges and opportunities for Portugal in the near future.
ENHANCING A SUSTAINABLE RURAL ECONOMIC DEVELOPMENT THROUGH SELF-HELP PROMOTION STRATEGY

The success of a sustainable poverty reduction in sub-Saharan African countries is based on socio-economic activities of rural communities that are characterised by participatory actions and group performance. The actions are mostly championed by various socio-cultural/socioeconomic groups in the communities. To translate rural economic development initiatives into sustainable project development for poverty reduction will therefore require working with existing structures in the rural communities. This article examines the concept of selfhelp organisations in the rural communities of developing countries, especially Nigeria. The article equally highlights the significant roles of these organisations, and particularly their contributions to the socio-economic development of their various communities. The article also analyses the approaches of government development agencies to the socio-economic development of rural communities and proposes a better role for them. The article then describes how performance effectiveness can be enhanced by the government development agencies in their proposed new role. Keywords: Self-help promotion, institution, sustainable development, monitoring, selfevaluation
The angiopoietin/Tie-2 system regulates pericyte survival and recruitment in diabetic retinopathy.

PURPOSE The angiopoietin (Ang) system plays an important role in vascular stabilization and pathologic neovascularization. The hypothesis for the study was that, in addition to modulating endothelial cell behavior, the angiopoietin/Tie-2 system also regulates the pericyte apoptosis and/or the vessel maturation associated with diabetic retinopathy. METHODS Tie-2 expression in cultured retinal pericytes was analyzed by using ELISA, Western Blot analysis, and flow cytometry. CD13 (aminopeptidase N) expression in pericytes was determined by Western blot analysis and Ang effects verified with Tie-2 antisense treatment. Cell proliferation was monitored by crystal violet uptake, and pericyte migration was assessed in a scrape wound. Annexin V-FITC flow cytometry was used to quantify pericyte apoptosis. RESULTS Pericytes expressed a functionally active Tie-2 receptor upregulated by both Ang-1 and -2 (P < 0.05). In pericytes undergoing apoptosis induced by either TNF-alpha or high glucose Ang-1 increased survival (P < 0.05 for TNF-alpha; P < 0.01 for high glucose), whereas Ang-2 increased apoptosis. Ang-1 enhanced CD13 expression in a dose-dependent manner (P < 0.05) and stimulated pericyte migration in a synthetic matrix wound-healing assay that was associated with a change in F-actin organization. Addition of Tie-2 antisense confirmed that angiopoietins act through Tie-2. CONCLUSIONS These findings demonstrate that Tie-2 is functional in pericytes and may play an important role in the progression of diabetic retinopathy, by regulating pericyte loss and influencing the activation state and recruitment of pericytes.
Development of the coronary vasculature and its implications for coronary abnormalities in general and specifically in pulmonary atresia without ventricular septal defect

Aim: Coronary vascular anomalies are an important factor in congenital heart disease in the neonate. However, our knowledge of the pathomorphogenesis is still defective. Material and methods: 1) Study of coronary anomaly variations in congenital heart disease using specimens and 2) study of the role of epicardium‐derived cells (EPDC) and neural crest cells in coronary vascular formation using quail‐chicken chimeras. Results: The clinical and pathological data revealed the existence of ventriculo‐coronary arterial communications during fetal life before pulmonary atresia was established. This supported a primary coronary developmental anomaly as the origin of some cases of pulmonary atresia as opposed to other cases in which the pulmonary orifice atresia was the primary anomaly. Our experimental work showed the high relevance of the development of the epicardium and epicardium‐derived cells for the formation of the coronary vasculature, and showed the coronary vascular ingrowth into the myocardium and subsequently into the aorta and the right atrium. The absence of epicardium‐derived cells leads to embryonic death, while delayed outgrowth could result in the absence of the main coronary arteries to pinpoint orifice formation. In these cases, the circulation was maintained through ventriculocoronary arterial communications. Neural crest cells were important for the patterning of the coronary vasculature. We have extended this knowledge to a number of other heart malformations.
Urine iodine measurements, creatinine adjustment, and thyroid deficiency in an adult United States population.

PURPOSE The purpose of the study was to explore the relationships between urine iodine, creatinine, serum TSH, and total T(4) in a diverse population of U.S. adults with the aim of determining whether low urine iodine is associated with thyroid deficiency. METHODS Using the Health and Nutrition Surveys III data set, we examined median TSH and total T(4) values according to deciles of urine iodine (with and without creatinine correction). Stepwise regression analysis was used to further explore these relationships in the context of possible confounding variables. Exclusion criteria included age less than 21 yr, pregnancy, and the presence of thyroid antibodies. RESULTS Among the 5963 men and 5722 women, median urine iodine concentrations do not vary with increasing age, whereas median creatinine levels decrease (P < 0.001). Urine iodine and creatinine concentrations are lower among women (P < 0.001). TSH increases with age (P < 0.001), whereas total T(4) decreases (P < 0.001). Neither TSH nor total T(4) median values are associated with urine iodine. If the urine iodine to creatinine ratio is used instead, an extensive redistribution of study subjects occurs that results in an apparent positive relationship between this ratio and TSH measurements. A multivariate regression analysis that accounts for age, body mass index, race, creatinine, iodine, estrogen use, smoking, and gender reveals only a weak association between levels of urine iodine and markers of thyroid function. CONCLUSIONS Our analyses indicate that the U.S. nonpregnant adult population is iodine sufficient.
Clathrin localization and dynamics in Aspergillus nidulans

Cell growth necessitates extensive membrane remodeling events including vesicle fusion or fission, processes that are regulated by coat proteins. The hyphal cells of filamentous fungi concentrate both exocytosis and endocytosis at the apex. This investigation focuses on clathrin in Aspergillus nidulans, with the aim of understanding its role in membrane remodeling in growing hyphae. We examined clathrin heavy chain (ClaH‐GFP) which localized to three distinct subcellular structures: late Golgi (trans‐Golgi equivalents of filamentous fungi), which are concentrated just behind the hyphal tip but are intermittently present throughout all hyphal cells; the region of concentrated endocytosis just behind the hyphal apex (the “endocytic collar”); and small, rapidly moving puncta that were seen trafficking long distances in nearly all hyphal compartments. ClaH localized to distinct domains on late Golgi, and these clathrin “hubs” dispersed in synchrony after the late Golgi marker PHOSBP. Although clathrin was essential for growth, ClaH did not colocalize well with the endocytic patch marker fimbrin. Tests of FM4‐64 internalization and repression of ClaH corroborated the observation that clathrin does not play an important role in endocytosis in A. nidulans. A minor portion of ClaH puncta exhibited bidirectional movement, likely along microtubules, but were generally distinct from early endosomes.
Role of Magnetic Resonance Imaging in the Assessment of Pediatric Cervical Spine Injuries

The purpose of this study was to determine the role of magnetic resonance imaging (MRI) in the evaluation of children with suspected cervical spine injury (CSI). The authors studied 237 consecutive children, 74 of whom were evaluated by MRI based on a trauma protocol of the authors' institution. The criteria for MRI were: (1) an obtunded or nonverbal child suspected of having CSI, (2) equivocal plain films, (3) neurologic symptoms without radiographic findings, or (4) an inability to clear the cervical spine within 3 days, based on testing. The average age of the evaluated children was 8 years. MRI confirmed the plain radiography diagnosis in 66% of children and altered the diagnosis in 34%. MRI is valuable in the evaluation of potential CSI, especially in obtunded children or children with equivocal plain radiographs.