bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pearls and pitfalls in experimental models of spreading depression
Authors: Ayata Cenk 
Published: May 2013

Background Spreading depression (SD) is the electrophysiological substrate of migraine aura and a potential trigger for headache. Since its discovery by Leão in 1944, SD has transformed from being viewed as an epiphenomenon into a therapeutic target relevant in the pathophysiology of migraine and brain injury. Aim Despite decades of research, the underpinnings of SD are still poorly understood, hampering our efforts to selectively block its initiation and spread. Experimental models have nevertheless been useful to measure the likelihood of SD occurrence (i.e. SD susceptibility) and characterize genetic, physiological and pharmacological modulation of SD in search of potential therapies, such as in migraine prophylaxis and stroke. Here, I review experimental SD susceptibility endpoints and surrogates, and minimum essential model requirements to improve their utility in drug screening. Conclusion A critical reappraisal of strengths and caveats of experimental models of SD susceptibility is needed to set standards and improve data quality, interpretation and reconciliation.
Pearls and pitfalls in human pharmacological models of migraine: 30 years' experience
Authors: Ashina Messoud , Hansen Jakob Møller , Olesen Jes 
Published: May 2013

In vitro studies have contributed to the characterization of receptors in cranial blood vessels and the identification of new possible anti-migraine agents. In vivo animal models enable the study of vascular responses, neurogenic inflammation, peptide release and genetic predisposition and thus have provided leads in the search for migraine mechanisms. All animal-based results must, however, be validated in human studies because so far no animal models can predict the efficacy of new therapies for migraine. Given the nature of migraine attacks, fully reversible and treatable, the headache- or migraine-provoking property of naturally occurring signaling molecules can be tested in a human model. If such an endogenous substance can provoke migraine in human patients, then it is likely, although not certain, that blocking its effect will be effective in the treatment of acute migraine attacks. To this end, a human in vivo model of experimental headache and migraine in humans has been developed. Human models of migraine offer unique possibilities to study mechanisms responsible for migraine and to explore the mechanisms of action of existing and future anti-migraine drugs. The human model has played an important role in translational migraine research leading to the identification of three new principally different targets in the treatment of acute migraine attacks and has been used to examine other endogenous signaling molecules as well as genetic susceptibility factors. New additions to the model, such as advanced neuroimaging, may lead to a better understanding of the complex events that constitute a migraine attack, and better and more targeted ways of intervention.
Deletion of the NF-κB subunit p65/RelA in the hematopoietic compartment leads to defects in hematopoietic stem cell function
Authors: Stein Sarah J. , Baldwin Albert S. 
Published: May 2013

Key Points
p65 is an important factor in hematopoiesis through the regulation of hematopoietic stem cell function and lineage commitment. p65 controls the expression of genes encoding key factors that promote hematopoietic stem cell homeostasis.
Genetic analysis and epidemiology of Crimean Congo hemorrhagic fever viruses in Baluchistan province of Pakistan
Authors: Alam Muhammad Masroor , Khurshid Adnan , Sharif Salmaan , Shaukat Shahzad , Rana Muhammad Suleman , Angez Mehar , Zaidi Syed Sohail Zahoor 
Published: May 2013

AbstractBackgroundPakistan is considered as an endemic country for Crimean-Congo Hemorrhagic fever with numerous outbreaks and sporadic cases reported during the past two decades. Majority of cases are reported from Baluchistan province with subsequent transmissions to non-endemic regions mainly through infected animals directly or via infested ticks. We hereby describe the molecular investigations of CCHF cases reported during 2008 in Quetta city of Baluchistan province.MethodsSerum Samples from 44 patients, with clinical signs of hemorrhagic fever attending a tertiary care hospital in Quetta city, were collected and tested for CCHF virus antigen and genomic RNA, using capture IgM EIA kit and standard RT-PCR assay, respectively. The partial S-gene fragments were directly sequenced to get information related to the prevailing CCHFV genotypes and their molecular epidemiology in Pakistan.ResultsOut of the total forty four, sixteen (36%) samples were found positive for CCHF IgM. Similarly, viral RNA was detected in six (16%) samples. Phylogenetic analysis revealed that all study viruses belong to genotype Asia-1 with closest similarity (99-100%) to the previously reported strains from Pakistan, Afghanistan and Iran.ConclusionWe conclude that CCHF virus remains endemic within Baluchistan and its neighboring regions of Afghanistan warranting a need of incessant surveillance activities.
Methods to increase participation in organised screening programs: a systematic review
Authors: Camilloni Laura , Ferroni Eliana , Cendales Beatriz Jimenez , Pezzarossi Annamaria , Furnari Giacomo , Borgia Piero , Guasticchi Gabriella , Rossi Paolo Giorgi ,   the Methods to increase participation Working Group
Published: May 2013

AbstractBackgroundThe European Community recommends the implementation of population-based screening programmes for cervical, breast, and colorectal cancers. This recommendation is supported by many observational studies showing that organised programmes effectively reduce mortality and control the inappropriate use of screening tests. We conducted a systematic review of studies assessing the efficacy of interventions to increase participation in organised population-based screening programs.MethodsWe included all studies on interventions aimed at increasing screening participation published between 1/1999 and 7/2012. For those published before 1999, we considered the Jepson et al. (2000) review (Health Technol Assess 4:1-133, 2000).ResultsIncluding studies from the Jepson review, we found 69 with quantitative information on interventions in organised screening: 19 for cervical, 26 for breast, 20 colorectal cancers, and 4 for cervical and breast cancer together.Effective interventions were: postal (breast RR = 1,37 95% Confidence Interval (95% CI): 1.25-1.51; cervical RR = 1.71 95% CI: 1.60-1.83; colorectal RR = 1.33 95% CI: 1.17-1.51) and telephone reminders (with heterogeneous methods for implementation); GP’s signature on invitation letter (breast RR = 1.13 95% CI: 1.11-1.16; cervical RR = 1.20 95% CI: 1.10-1.30; colorectal RR = 1.15 95% CI: 1.07-1.24); scheduled appointment instead of open appointment (breast RR = 1.26 95% CI: 1.02-1.55; cervical RR = 1.49 95% CI: 1.27-1.75; colorectal RR = 1.79 95% CI: 1.65-1.93). Mailing a kit for self-sampling cervical specimens increased participation in non-responders (RR = 2.37 95% CI: 1.44-3.90).ConclusionAlthough some interventions did prove to be effective, some specific variables may influence their effectiveness in and applicability to organised population-based screening programs.
The impact of discrete modes of spinal cord injury on bladder muscle contractility
Authors: Seth Abhishek , Chung Yeun Goo , Kim Daniel , Ramachandran Aruna , Cristofaro Vivian , Gomez III Pablo , Tu Duong , Huang Lin , Benowitz Larry I , Di Vizio Dolores , Sullivan Maryrose P , Adam Rosalyn M 
Published: May 2013

AbstractBackgroundPrior studies have compared the effect of spinal cord injury elicited using distinct approaches on motor and visceral function. However, the impact of such discrete modes of injury specifically on bladder muscle contractility has not been explored in detail. The goal of this study is to compare the impact of complete spinal cord transection versus clip compression at thoracic vertebra eight (T8) on bladder muscle contractility.MethodsRats underwent no treatment (Control), laminectomy (Sham, SH); complete extradural transection (TX); or cord compression with an aneurysm clip (CX). Bladders and spinal cords were harvested at 6 wk for contractility studies or histological analysis.ResultsDetrusor strips from TX and CX rats showed higher spontaneous activity than those from SH rats. Furthermore, the duration of the neurally-mediated contractile response was longer in TX and CX rats compared to controls and showed attenuated relaxation. No significant differences were observed between muscle strips from SH, TX or CX rats in response to KCl, ATP or phenylephrine. However, tissues from TX and CX rats showed a higher sensitivity to carbachol compared to that from SH animals.ConclusionsComplete SCI in rats either by cord transection or compression elicits qualitatively similar changes in bladder muscle contractility. Whereas cord transection is arguably easier to perform experimentally, cord compression better models the situation observed clinically, such that each approach has clear advantages and limitations.
Genome scan study of prostate cancer in Arabs: identification of three genomic regions with multiple prostate cancer susceptibility loci in Tunisians
Authors: Shan Jingxuan , Al-Rumaihi Khalid , Rabah Danny , Al-Bozom Issam , Kizhakayil Dhanya , Farhat Karim , Al-Said Sami , Kfoury Hala , Dsouza Shoba P , Rowe Jillian , Khalak Hanif G , Jafri Shahzad , Aigha Idil I , Chouchane Lotfi 
Published: May 2013

Abstract

Background
Large databases focused on genetic susceptibility to prostate cancer have been accumulated from population studies of different ancestries, including Europeans and African-Americans. Arab populations, however, have been only rarely studied.

Methods
Using Affymetrix Genome-Wide Human SNP Array 6, we conducted a genome-wide association study (GWAS) in which 534,781 single nucleotide polymorphisms (SNPs) were genotyped in 221 Tunisians (90 prostate cancer patients and 131 age-matched healthy controls). TaqMan® SNP Genotyping Assays on 11 prostate cancer associated SNPs were performed in a distinct cohort of 337 individuals from Arab ancestry living in Qatar and Saudi Arabia (155 prostate cancer patients and 182 age-matched controls). In-silico expression quantitative trait locus (eQTL) analysis along with mRNA quantification of nearby genes was performed to identify loci potentially cis-regulated by the identified SNPs.

Results
Three chromosomal regions, encompassing 14 SNPs, are significantly associated with prostate cancer risk in the Tunisian population (P = 1 × 10-4 to P = 1 × 10-5). In addition to SNPs located on chromosome 17q21, previously found associated with prostate cancer in Western populations, two novel chromosomal regions are revealed on chromosome 9p24 and 22q13. eQTL analysis and mRNA quantification indicate that the prostate cancer associated SNPs of chromosome 17 could enhance the expression of STAT5B gene.

Conclusion
Our findings, identifying novel GWAS prostate cancer susceptibility loci, indicate that prostate cancer genetic risk factors could be ethnic specific.
Positive solutions for Sturm-Liouville BVPs on time scales via sub-supersolution and variational methods
Authors: Zhang Quan-Guo , He Xi-Ping , Sun Hong-Rui 
Published: May 2013

Abstract
This paper is concerned with the existence of one and two positive solutions for the following Sturm-Liouville boundary value problem on time scales

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MSC:34B10, 34B18.
TGF-β1 Sensitizes TRPV1 through Cdk5 Signaling in Odontoblast-Like Cells
Authors: Utreras Elias , Prochazkova Michaela , Terse Anita , Gross Jacklyn , Keller Jason , Iadarola Michael J , Kulkarni Ashok B 
Published: May 2013

Background Odontoblasts are specialized cells that form dentin and they are believed to be sensors for tooth pain. Transforming growth factor-β1 (TGF-β1), a pro-inflammatory cytokine expressed early in odontoblasts, plays an important role in the immune response during tooth inflammation and infection. TGF-β1 is also known to participate in pain signaling by regulating cyclin-dependent kinase 5 (Cdk5) in nociceptive neurons of the trigeminal and dorsal root ganglia. However, the precise role of TGF-β1 in tooth pain signaling is not well characterized. The aim of our present study was to determine whether or not in odontoblasts Cdk5 is functionally active, if it is regulated by TGF-β1, and if it affects the downstream pain receptor, transient receptor potential vanilloid-1 (TRPV1). Results We first determined that Cdk5 and p35 are indeed expressed in an odontoblast-enriched primary preparation from murine teeth. For the subsequent analysis, we used an odontoblast-like cell line (MDPC-23) and found that Cdk5 is functionally active in these cells and its kinase activity is upregulated during cell differentiation. We found that TGF-β1 treatment potentiated Cdk5 kinase activity in undifferentiated MDPC-23 cells. SB431542, a specific inhibitor of TGF-β1 receptor 1 (Tgfbr1), when co-administered with TGF-β1, blocked the induction of Cdk5 activity. TGF-β1 treatment also activated the ERK1/2 signaling pathway, causing an increase in early growth response-1 (Egr-1), a transcription factor that induces p35 expression. In MDPC-23 cells transfected with TRPV1, Cdk5-mediated phosphorylation of TRPV1 at threonine-407 was significantly increased after TGF-β1 treatment. In contrast, SB431542 co-treatment blocked TRPV1 phosphorylation. Moreover, TGF-β1 treatment enhanced both proton- and capsaicin-induced Ca2+ influx in TRPV1-expressing MDPC-23 cells, while co-treatment with either SB431542 or roscovitine blocked this effect. Conclusions Cdk5 and p35 are expressed in a murine odontoblast-enriched primary preparation of cells from teeth. Cdk5 is also functionally active in odontoblast-like MDPC-23 cells. TGF-β1 sensitizes TRPV1 through Cdk5 signaling in MDPC-23 cells, suggesting the direct involvement of odontoblasts and Cdk5 in dental nociceptive pain transduction.
Necrotizing sarcoid granulomatosis with hemoptysis: a case report and literature review
Authors: Huang Haidong , Li Chen , Bai Chong , Li Qiang , Zheng Weiqiang , Zhu Zhi , Zarogoulidis Paul , Zarogoulidis Konstantinos , Gschwendtner Andreas , Hohenforst-Schmidt Wolfgang , Simoff Michael 
Published: May 2013

Abstract

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1955868163936338

We present a case of 39-year-old male with the symptoms of fever, cough, chest pain and bloody phlegm, whose chest CT showed multiple subpleural nodules and inflammatory infiltration. Video-Assisted Thoracic Surgery ( VATS ) for right subplural nodule was performed and confirmed the diagnosis of necrotizing sarcoid granulomatosis. Prednisolone was administered and the symptoms were under control untill the occurrence of intermittent hemoptysis after 10 months. Chest CT and bronchoscope revealed the right lower lobe nodule with intraluminal necrotic tissue in the right lower lobe posterior basal segment respectively. Fatal hemoptysis happened during endobronchial biopsy by flexible bronchoscope forcep. Based on this case, we reviewed the relevant literature and discussed the clinical features, pathological changes and prognosis of the disease.
Congenital asymptomatic diaphragmatic hernias in adults: a case series
Authors: Bianchi Enrica , Mancini Paola , De Vito Stefania , Pompili Elena , Taurone Samanta , Guerrisi Isabella , Guerrisi Antonino , D’Andrea Vito , Cantisani Vito , Artico Marco 
Published: May 2013

Abstract

Introduction
Congenital diaphragmatic hernia is a major malformation occasionally found in newborns and babies. Congenital diaphragmatic hernia is defined by the presence of an orifice in the diaphragm, more often to the left and posterolateral, that permits the herniation of abdominal contents into the thorax. The aim of this case series is to provide information on the presentation, diagnosis and outcome of three patients with late-presenting congenital diaphragmatic hernias. The diagnosis of congenital diaphragmatic hernia is based on clinical investigation and is confirmed by plain X-ray films and computed tomography scans.

Case presentations
In the present report three cases of asymptomatic abdominal viscera herniation within the thorax are described. The first case concerns herniation of some loops of the large intestine into the left hemi-thorax in a 75-year-old Caucasian Italian woman. The second case concerns a rare type of herniation in the right side of the thorax of the right kidney with a part of the liver parenchyma in a 57-year-old Caucasian Italian woman. The third case concerns herniation of the stomach and bowel into the left side of the chest with compression of the left lung in a 32-year-old Caucasian Italian man. This type of hernia may appear later in life, because of concomitant respiratory or gastrointestinal disease, or it may be an incidental finding in asymptomatic adults, such as in the three cases featured here.

Conclusions
Patients who present with late diaphragmatic hernias complain of a wide variety of symptoms, and diagnosis may be difficult. Additional investigation and research appear necessary to better explain the development and progression of this type of disease.
Induction of long intergenic non-coding RNA HOTAIR in lung cancer cells by type I collagen
Authors: Zhuang Yan , Wang Xiang , Nguyen Hong T , Zhuo Ying , Cui Xinpeng , Fewell Claire , Flemington Erik K , Shan Bin 
Published: May 2013

Abstract

Background
The tumor microenvironment is a crucial determinant in tumor progression. Interstitial extracellular matrix (ECM), such as type I collagen (Col-1), is aberrantly enriched in the tumor microenvironment and promotes tumor progression. Long intergenic non-coding RNAs (lincRNA) are a new family of regulatory RNAs that modulate fundamental cellular processes via diverse mechanisms.

Findings
We investigated whether the expression of lincRNAs was regulated by the tumor promoting Col-1. In a three-dimensional organotypic culture model using the reconstituted basement membrane ECM Matrigel (rBM 3-D), supplementation of Col-1 disrupted acini, a differentiation feature of well-differentiated lung adenocarcinoma cells, and concurrently induced the expression of a tumor-promoting lincRNA, HOX transcript antisense RNA (HOTAIR). Induction of HOTAIR by Col-1 was diminished by a neutralizing antibody against the Col-1 receptor α2β1 integrin. Col-1 activates the expression of a reporter gene controlled by the human HOTAIR promoter. Moreover the expression of HOTAIR and Col-1 was concurrently up-regulated in human non-small cell lung cancer.

Conclusions
Our findings indicate that tumor-promoting Col-1 up-regulates the expression of HOTAIR in NSCLC cells. These initial results warrant further investigation of HOTAIR and other lincRNA genes in lung tumorigenesis.
Anti-Vascular endothelial growth factor therapy impairs endothelial function of retinal microcirculation in colon cancer patients – an observational study
Authors: Reimann Manja , Folprecht Gunnar , Haase Rocco , Trautmann Karolin , Ehninger Gerhard , Reichmann Heinz , Ziemssen Focke , Ziemssen Tjalf 
Published: May 2013

Abstract

Background
To assess acute effects of bevacizumab (anti-VEGF therapy) on cerebral microvessels and systemic cardiovascular regulation.

Design and subjects
20 consecutive patients with colorectal cancer (median age: 60.4 years, range 45.5-73.9 years) received bevacizumab intravenously (5 mg/kg) uncoupled of chemotherapy. Prior to and within the first 24 hours after bevacizumab infusion, patients were investigated for retinal endothelial function. A series of a triple 24-hour ambulatory blood pressure measurement was conducted. Retinal endothelial function was determined as flicker light-induced vasodilation. The integrity of baroreflex arc and autonomic cardiovascular control was examined by stimulatory manoeuvres.

Results
Bevacizumab therapy significantly reduced the vasodilatory capacity of retinal arterioles in response to flicker light. A slight decrease in diastolic pressure and heart rate was observed after bevacizumab infusion but this was unrelated to changes in retinal function. The pressure response upon nitroglycerin was largely preserved after bevacizumab infusion. The proportion of patients with abnormal nocturnal blood pressure regulation increased under anti-angiogenic therapy. Autonomic blood pressure control was not affected by bevacizumab treatment.

Conclusions
Bevacizumab acutely impairs microvascular function independent of blood pressure changes. Imaging of the retinal microcirculation seems a valuable tool for monitoring pharmacodynamic effects of bevacizumab.

Trial registration
NCT ID: NCT00740168
Where is the grass greener? A micro-founded model of migration with application to Guangdong
Authors: Simmons Peter , Xie Yuanyuan 
Published: May 2013

Abstract

Abstract
This paper first develops a structural micro-founded model of aggregate net migration flow using matching ideas to study how migrants choose between multiple locations using multiple criteria. Migration should reduce inequality in the criteria. Most migration models either do not handle multiple criteria and locations or lack micro foundation. The model predicts that migration flows will be out of all but the top two ranked regions. The empirical work, which uses 1990–1999 Guangdong annual data, confirms this proposition and finds a high degree of common marginal effects of the criteria among 18 locations but also finds increasing regional inequalities.

JEL
F22 J61 O15
Preparation, Crystal Structure, and Spectroscopic, Chemical, and Electrochemical Properties of (2E,4E)-1-(3-Guaiazulenyl)-4-(2-thienyl)-1,3-butadiene
Authors: Takekuma Shin-ichi , Kobayashi Norihito , Minematsu Toshie , Takekuma Hideko 
Published: May 2013

Abstract
Wittig reaction of (E)-2-(2-thienyl)ethylene-1-carbaldehyde with [(3-guaiazulenyl)methyl]triphenylphosphonium bromide in ethanol containing sodium ethoxide (=NaOC2H5) at 25 °C for 24 h under argon gives the two (2E,4E)- and (2E,4Z)-geometric isomers of a new compound 1-(3-guaiazulenyl)-4-(2-thienyl)-1,3-butadiene, the only title (2E,4E)-form, of which can be isolated as single crystals. Preparation, chemical and spectroscopic properties, crystal structure, and electrochemical behavior of the target (2E,4E)-form, compared with those of (E)-1-(3-guaiazulenyl)-2-(2-thienyl)ethylene and the structurally related new compound (3-guaiazulenyl)[(E)-2-(2-thienyl)ethenyl]methylium hexafluorophosphate, are documented.