bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic Ethanol Consumption Modulates Growth Factor Release, Mucosal Cytokine Production, and MicroRNA Expression in Nonhuman Primates
Authors: Asquith Mark , Pasala Sumana , Engelmann Flora , Haberthur Kristen , Meyer Christine , Park Byung , Grant Kathleen A. , Messaoudi Ilhem 
Published: December 2013

BackgroundChronic alcohol consumption has been associated with enhanced susceptibility to both systemic and mucosal infections. However, the exact mechanisms underlying this enhanced susceptibility remain incompletely understood.MethodsUsing a nonhuman primate model of ethanol (EtOH) self‐administration, we examined the impact of chronic alcohol exposure on immune homeostasis, cytokine, and growth factor production in peripheral blood, lung, and intestinal mucosa following 12 months of chronic EtOH exposure.ResultsEtOH exposure inhibited activation‐induced production of growth factors hepatocyte growth factor (HGF), granulocyte colony‐stimulating factor (G‐CSF), and vascular‐endothelial growth factor (VEGF) by peripheral blood mononuclear cells (PBMC). Moreover, EtOH significantly reduced the frequency of colonic Th1 and Th17 cells in a dose‐dependent manner. In contrast, we did not observe differences in lymphocyte frequency or soluble factor production in the lung of EtOH‐consuming animals. To uncover mechanisms underlying reduced growth factor and Th1/Th17 cytokine production, we compared expression levels of microRNAs in PBMC and intestinal mucosa. Our analysis revealed EtOH‐dependent up‐regulation of distinct microRNAs in affected tissues (miR‐181a and miR‐221 in PBMC; miR‐155 in colon). Moreover, we were able to detect reduced expression of the transcription factors STAT3 and ARNT, which regulate expression of VEGF, G‐CSF, and HGF and contain targets for these microRNAs. To confirm and extend these observations, PBMC were transfected with either mimics or antagomirs of miR‐181 and miR‐221, and protein levels of the transcription factors and growth factors were determined. Transfection of microRNA mimics led to a reduction in both STAT3/ARNT as well as VEGF/HGF/G‐CSF levels. The opposite outcome was observed when microRNA antagomirs were transfected.ConclusionsChronic EtOH consumption significantly disrupts both peripheral and mucosal immune homeostasis, and this dysregulation may be mediated by changes in microRNA expression.
Greater externalizing personality traits predict less error‐related insula and anterior cingulate cortex activity in acutely abstinent cigarette smokers
Authors: Carroll Allison J. , Sutherland Matthew T. , Salmeron Betty Jo , Ross Thomas J. , Stein Elliot A. 
Published: December 2013

AbstractAttenuated activity in performance‐monitoring brain regions following erroneous actions may contribute to the repetition of maladaptive behaviors such as continued drug use. Externalizing is a broad personality construct characterized by deficient impulse control, vulnerability to addiction and reduced neurobiological indices of error processing. The insula and dorsal anterior cingulate cortex (dACC) are regions critically linked with error processing as well as the perpetuation of cigarette smoking. As such, we examined the interrelations between externalizing tendencies, erroneous task performance, and error‐related insula and dACC activity in overnight‐deprived smokers (n = 24) and non‐smokers (n = 20). Participants completed a self‐report measure assessing externalizing tendencies (Externalizing Spectrum Inventory) and a speeded Flanker task during functional magnetic resonance imaging scanning. We observed that higher externalizing tendencies correlated with the occurrence of more performance errors among smokers but not non‐smokers. Suggesting a neurobiological contribution to such suboptimal performance among smokers, higher externalizing also predicted less recruitment of the right insula and dACC following error commission. Critically, this error‐related activity fully mediated the relationship between externalizing traits and error rates. That is, higher externalizing scores predicted less error‐related right insula and dACC activity and, in turn, less error‐related activity predicted more errors. Relating such regional activity with a clinically relevant construct, less error‐related right insula and dACC responses correlated with higher tobacco craving during abstinence. Given that inadequate error‐related neuronal responses may contribute to continued drug use despite negative consequences, these results suggest that externalizing tendencies and/or compromised error processing among subsets of smokers may be relevant factors for smoking cessation success.
Expression and in situ localization of GATA4, 5 and 6 mRNAs in ovine conceptuses and uterine endometria during the peri‐implantation period
Authors: Bai Hanako , Sakurai Toshihiro , Godkin James D. , Imakawa Kazuhiko 
Published: December 2013

AbstractIn vertebrates, six GATA transcription factors, GATA1 through GATA6, have been identified and GATA1‐3 is known to be involved in hematopoietic developments, while GATA4‐6 play roles in cardiac and endoderm developments. Recently, we and others have found that GATA2 and GATA3 found in the trophectoderm plays a role in gene expression specific to this cell type, but GATA4‐6 have not been well characterized in early embryonic developments. Using quantitative polymerase chain reaction (qPCR) and in situ hybridization, we examined the expression of GATA4, 5 and 6 messenger RNAs (mRNAs) in ovine conceptuses and uteri during the peri‐implantation period. In ovine conceptuses, GATA4, 5 and 6 transcripts were present on days 15, 17 and 21 (day 0 = day of mating), and high GATA5 and 6 mRNAs were found on day 21, most of which were localized in the trophectoderm and endoderm. Moreover, minute and substantial GATA4 and 5 mRNAs were found in days 15 and 21 uterine endometria, respectively. Increase in GATA4‐6 transcripts in day 21 uteri indicates that in addition to GATA1‐3, GATA4‐6 may also play a potentially novel role in the development of ovine trophectoderm, endoderm and/or uterine endometria following conceptus attachment to the uterine epithelium.
Genetic selection for resistance to mycoplasmal pneumonia of swine (MPS) in the Landrace line influences the expression of soluble factors in blood after MPS vaccine sensitization
Authors: Shimazu Tomoyuki , Borjigin Liushiqi , Katayama Yuki , Li Meihua , Satoh Takumi , Watanabe Kouichi , Kitazawa Haruki , Roh Sang‐gun , Aso Hisashi , Kazuo Katoh , Suda Yoshihito , Sakuma Akiko , Nakajo Mituru , Suzuki Keiichi 
Published: December 2013

AbstractWe recently developed a Landrace line that is resistant to mycoplasmal pneumonia of swine (MPS) infection by genetic selection for five generations, and we reported that the immunophenotype of this line is different from that of the non‐selected line in terms of changes in peripheral blood leukocyte population after MPS vaccination. This study followed up previous findings demonstrating changes in soluble factors in blood, namely, hormones, Mycoplasma hyopneumoniae‐specific immunoglobulin G (IgG), and cytokines. These two lines were injected with MPS vaccine on days −7 and 0 after blood sampling on those days, and blood samples were collected on days −14, −7, 0, 2, 7 and 14. We found changes in the levels of many hormones and cytokines in both lines. However, we found that only growth hormone (GH) and interferon (IFN)‐γ levels were statistically different between these two lines. GH concentration was reduced (day 0) and IFN‐γ concentration was increased (day 14) in the MPS‐selected line compared with the non‐selected line, despite unchanged IFN‐γ messenger RNA expression in blood cells. Although detailed mechanisms underlying these phenotypes remain unsolved, these traits would be useful to improve MPS resistance in pig production and provide an insight into MPS infection.
Immunomodulatory agents lenalidomide and pomalidomide co‐stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4CRBN
Authors: Gandhi Anita K. , Kang Jian , Havens Courtney G. , Conklin Thomas , Ning Yuhong , Wu Lei , Ito Takumi , Ando Hideki , Waldman Michelle F. , Thakurta Anjan , Klippel Anke , Handa Hiroshi , Daniel Thomas O. , Schafer Peter H. , Chopra Rajesh 
Published: December 2013

SummaryCereblon (CRBN), the molecular target of lenalidomide and pomalidomide, is a substrate receptor of the cullin ring E3 ubiquitin ligase complex, CRL4CRBN. T cell co‐stimulation by lenalidomide or pomalidomide is cereblon dependent: however, the CRL4CRBN substrates responsible for T cell co‐stimulation have yet to be identified. Here we demonstrate that interaction of the transcription factors Ikaros (IKZF1, encoded by the IKZF1 gene) and Aiolos (IKZF3, encoded by the IKZF3 gene) with CRL4CRBN is induced by lenalidomide or pomalidomide. Each agent promotes Aiolos and Ikaros binding to CRL4CRBN with enhanced ubiquitination leading to cereblon‐dependent proteosomal degradation in T lymphocytes. We confirm that Aiolos and Ikaros are transcriptional repressors of interleukin‐2 expression. The findings link lenalidomide‐ or pomalidomide‐induced degradation of these transcriptional suppressors to well documented T cell activation. Importantly, Aiolos could serve as a proximal pharmacodynamic marker for lenalidomide and pomalidomide, as healthy human subjects administered lenalidomide demonstrated Aiolos degradation in their peripheral T cells. In conclusion, we present a molecular model in which drug binding to cereblon results in the interaction of Ikaros and Aiolos to CRL4CRBN, leading to their ubiquitination, subsequent proteasomal degradation and T cell activation.
Decline in usually visiting the dentist for a problem in Australia, 1994 to 2010: an age–period–cohort analysis
Authors: Luzzi Liana , Chrisopoulos Sergio , Brennan David S. 
Published: December 2013

AbstractObjectivesTo determine the extent to which age, period and cohort factors have contributed to variation in problem‐oriented dental visiting over time.MethodsData were obtained from four National Dental Telephone Interview Surveys of Australian residents aged 5 years and over conducted in 1994, 1999, 2004 and 2010 (response rates 48–72%). The trend in the percentage of persons usually visiting the dentist for a problem was analysed by means of a standard cohort table and by a nested models framework for age–period–cohort analyses.ResultsThe percentage of persons usually visiting the dentist for a problem generally decreased over the periods examined (from 42.5% in 1994 to 31.5% in 2010). Problem visiting tended to be lower for children and adolescents compared with adult age groups at each point in time. Model fit tests revealed that the age–period–cohort model provided the best fit for the data (Hosmer–Lemeshow test statistic = 5.3; d.f. = 8; P‐value = 0.72), indicating that both period and cohort factors were influential in problem visiting.ConclusionThis study found similar, consistent stories for both the age–period and age–cohort models, with usually visiting for a problem tending to be higher in older age groups and older cohorts. Problem visiting tended to decline over time for most age groups and most age cohorts. Understanding patterns of dental service use over time can be used to help inform service delivery policies that promote and facilitate appropriate use of dental services.
The BRAFV600E mutation in papillary thyroid microcarcinoma: does the mutation have an impact on clinical outcome?
Authors: Walczyk Agnieszka , Kowalska Aldona , Kowalik Artur , Sygut Jacek , Wypiórkiewicz Elżbieta , Chodurska Renata , Pięciak Liliana , Góźdź Stanisław 
Published: December 2013

SummaryContextAn activating mutation in the gene BRAF has been correlated with poorer prognosis and more aggressive clinical course in papillary thyroid carcinoma (PTC). We therefore hypothesized that the good prognosis, high 5‐year disease‐free rate and high survival rate of patients with less aggressive papillary thyroid microcarcinoma (pT1aNo‐x) would be associated with a lower incidence of the BRAFV600E mutation.ObjectivesTo evaluate the frequency of the activating mutation BRAFV600E in low‐risk papillary thyroid microcarcinoma (pT1aNo‐x at the moment of diagnosis) and the association of the mutation with the clinical outcome in a retrospective analysis.Study DesignBRAFV600E was characterized in 113 PTC patients diagnosed with pT1aNo‐x (one PTC focus with a diameter <1 cm, without lymph node or distant metastases according to IUCC/AJCC TNM staging system 2010). Genotyping was performed on DNA extracted from thyroid tumour tissue using direct capillary sequencing, and allele‐specific amplification PCR was used to resolve equivocal results. Retrospective analysis of the clinical course of PTC was then correlated with BRAF status in the primary tumour tissue.ResultsThe BRAFV600E mutation was detected in 78 of the 113 pT1aNo‐x patients (69·0%). We observed no persistence, locoregional recurrence, lymph node or distant metastases or deaths in the study group during the 12‐year study (January 2001 to December 2012).ConclusionsThe presence of the activating BRAFV600E mutation in a significant percentage of papillary thyroid microcarcinoma indicates that further analyses are required to verify its usefulness as a predictor of clinical outcome in PTC. In this study, there was no correlation between BRAF‐positive primary focus of papillary microcarcinoma and more aggressive or recurrent disease.
Single incision laparoscopic right colectomy: a systematic review and meta‐analysis
Authors: Vettoretto N. , Cirocchi R. , Randolph J. , Parisi A. , Farinella E. , Romano G. 
Published: December 2013

AbstractAimA meta‐analysis was performed to compare the outcome of single incision laparoscopic right hemicolectomy with standard multiport laparoscopic right hemicolectomy.MethodA systematic search of databases was carried out to extract comparative studies (randomized and non‐randomized, prospective and retrospective). Data were analysed according to Cochrane Collaboration guidelines. A meta‐analysis was performed when the data permitted this form of analysis.ResultsNine comparative studies were retrieved comprising 241 patients with single incision and standard laparoscopy. None of these was randomized. There was no significant difference between the two methods for the primary end‐points of mortality, morbidity and cancer‐specific parameters and for the secondary end‐points of operation time, blood loss, ileus, hospital stay and conversion. It was not possible to analyse pain and cosmetics data owing to insufficient information.ConclusionSingle incision laparoscopic right hemicolectomy is comparable with standard multiport laparoscopic right hemicolectomy in primary and secondary outcomes. Given current information it is justified to use single incision laparoscopic right hemicolectomy, but there is a need for a prospective randomized study.
Barriers and facilitators to attending pre‐pregnancy care services: the ATLANTIC‐DIP experience
Authors: O'Higgins S. , McGuire B. E. , Mustafa E. , Dunne F. 
Published: December 2013

AbstractAimsPre‐pregnancy care programmes can help to reduce morbidity and mortality associated with pregnancy in women with diabetes. However, uptake of a free pre‐pregnancy care programme along the Irish Atlantic seaboard was only 30%. This study sought to better understand why women with diabetes mellitus (Type 1 and Type 2) choose to attend pre‐pregnancy care services and to identify perceived barriers to attendance.MethodsA participative health research method called the participative research process was used to facilitate 14 women with diabetes mellitus to create ‘webs of ideas’ on the reasons for attendance and non‐attendance at a pre‐pregnancy care programme, and potential solutions for each obstacle.ResultsThe participants identified information on the risks of pregnancy as crucial for all childbearing women with diabetes, as lack of information was a major obstacle to attendance at pre‐pregnancy care programmes. Practical constraints such as childcare difficulties and work commitments were also identified. Participants stressed that health practitioners need to focus on positive aspects of pregnancy and childbearing rather than focusing solely on the problematic aspects for women with diabetes mellitus.ConclusionsWomen with diabetes need support and reassurance about their ability to control blood glucose and have a successful pregnancy while coping with the multiple challenges inherent in diabetes management and pregnancy. To increase uptake of pre‐pregnancy care, a norm needs to be established that situates pre‐pregnancy care as something every woman with diabetes will do, whether or not she is actively contemplating becoming a mother at the time. Active use of social media and facilitating peer support should be encouraged in pre‐pregnancy services to facilitate attendance. The time has come to incorporate the skills of a clinical psychologist in the delivery of a pre‐pregnancy service.
Systems biology of human epilepsy applied to patients with brain tumors
Authors: Mittal Sandeep , Shah Aashit K. , Barkmeier Daniel T. , Loeb Jeffrey A. 
Published: December 2013

SummaryEpilepsy is a disease of recurrent seizures that can be associated with a wide variety of acquired and developmental brain lesions. Current medications for patients with epilepsy can suppress seizures; they do not cure or modify the underlying disease process. On the other hand, surgical removal of focal brain regions that produce seizures can be curative. This surgical procedure can be more precise with the placement of intracranial recording electrodes to identify brain regions that generate seizure activity as well as those that are critical for normal brain function. The detail that goes into these surgeries includes extensive neuroimaging, electrophysiology, and clinical data. Combined with precisely localized tissues removed, these data provide an unparalleled opportunity to learn about the interrelationships of many “systems” in the human brain not possible in just about any other human brain disorder. Herein, we describe a systems biology approach developed to study patients who undergo brain surgery for epilepsy and how we have begun to apply these methods to patients whose seizures are associated with brain tumors. A central goal of this clinical and translational research program is to improve our understanding of epilepsy and brain tumors and to improve diagnosis and treatment outcomes of both.
MRI in the diagnosis and management of epileptomas
Authors: Duncan John S. , de Tisi Jane 
Published: December 2013

SummaryHigh‐resolution magnetic resonance imaging (MRI) is invaluable for identifying cerebral tumors that cause epilepsy. Serial voxel‐based automated quantitative analyses are more sensitive than visual reading for detecting change in a lesion. Eloquent cortex can be identified with functional MRI (fMRI), with cautions about the precise location and extent of critical cortex. Tractography is useful for delineating critical white matter tracks as are MR venography and computerized tomography (CT) angiography for displaying veins and arteries. These data may be combined into a three‐dimensional (3D) multimodal MR data presentation and displayed interoperatively to increase the precision and minimize the risk of neurosurgical treatment, and for the illustrations.
Depths and grids in brain tumors: Implantation strategies, techniques, and complications
Authors: Sweet Jennifer A. , Hdeib Alia M. , Sloan Andrew , Miller Jonathan P. 
Published: December 2013

SummaryPatients with intracranial mass lesions are at increased risk of intractable epilepsy even after tumor resection due to the potential epileptogenicity of lesional and perilesional tissue. Risk factors for tumoral epilepsy include tumor location, histology, and extent of tumor resection. In epilepsy that occurs after tumor resection, the epileptogenic zone often does not correspond precisely with the area of abnormality on imaging, and seizures often arise from a relatively restricted area despite widespread changes on imaging. Invasive monitoring via subdural grids and/or depth electrodes can therefore be helpful to delineate areas of eloquence and localize the epileptogenic zone for subsequent resection. Subdural grids offer excellent contiguous coverage of superficial cortex and allow resection using the same craniotomy, facilitating understanding of anatomic relationships. Depth electrodes offer superior coverage of deep structures, are easier to use in cases where a previous craniotomy is present, are not associated with anatomic distortion due to brain shift, and may be associated with a lower complication rate. We review the biology of focal postoperative epilepsy and invasive diagnostic strategies for the surgical evaluation of medically refractory epilepsy in patients who have undergone resection of intracranial mass lesions.
Choosing the tumoral epilepsy surgery candidate
Authors: Rheims Sylvain , Ducray François , Ryvlin Philippe 
Published: December 2013

SummaryThe management of epilepsy is an essential clinical issue in many patients with brain tumors. Tumoral epilepsy is often drug resistant and is associated with poor quality of life. Surgery represents a key therapeutic option in the management of patients with refractory tumoral epilepsy, with high rates of postoperative seizure freedom, especially when gross total resection can be performed. The selection of surgical candidates first requires extrapolation of the presumed underlying pathology and its potential for malignant transformation from clinical and imaging data, especially MRI characteristics. These data determine the decision for surgery, as well as its timing and technical aspects in relation to the risk of postoperative deficit. In glioneuronal tumors, where seizures are often drug‐resistant and risk of malignant transformation is very low, epilepsy surgery is usually recommended to alleviate disabling seizures and side effects of antiepileptic drugs. However, the risk of postoperative deficit may outweigh potential benefits of surgery in tumors located within eloquent cortex. This issue is particularly relevant for glioneuronal tumors located within the dominant mesial temporal structures in patients in whom seizure control might require additional hippocampectomy, associated with a high risk of memory decline. In contrast, in patients with low‐grade gliomas or aggressive brain neoplasms, both the decision to perform surgery and selection of the best surgical approach primarily rely on the oncologic imperative rather than epileptologic considerations. In these patients, the extent of tumor resection correlates with improved survival, progression‐free survival, as well as with the chances of postoperative seizure control.