bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expansion of cardiac ischemia/reperfusion injury after instillation of three forms of multi-walled carbon nanotubes
Authors: Urankar Rakhee N , Lust Robert M , Mann Erin , Katwa Pranita , Wang Xiaojia , Podila Ramakrishna , Hilderbrand Susana C , Harrison Benjamin S , Chen Pengyu , Ke Pu Chun , Rao Apparao M , Brown Jared M , Wingard Christopher J 
Published: October 2012

Abstract

Background
The exceptional physical-chemical properties of carbon nanotubes have lead to their use in diverse commercial and biomedical applications. However, their utilization has raised concerns about human exposure that may predispose individuals to adverse health risks. The present study investigated the susceptibility to cardiac ischemic injury following a single exposure to various forms of multi-walled carbon nanotubes (MWCNTs). It was hypothesized that oropharyngeal aspiration of MWCNTs exacerbates myocardial ischemia and reperfusion injury (I/R injury).

Methods
Oropharyngeal aspiration was performed on male C57BL/6J mice with a single amount of MWCNT (0.01 - 100 μg) suspended in 100 μL of a surfactant saline (SS) solution. Three forms of MWCNTs were used in this study: unmodified, commercial grade (C-grade), and functionalized forms that were modified either by acid treatment (carboxylated, COOH) or nitrogenation (N-doped) and a SS vehicle. The pulmonary inflammation, serum cytokine profile and cardiac ischemic/reperfusion (I/R) injury were assessed at 1, 7 and 28 days post-aspiration.

Results
Pulmonary response to MWCNT oropharyngeal aspiration assessed by bronchoalveolar lavage fluid (BALF) revealed modest increases in protein and inflammatory cell recruitment. Lung histology showed modest tissue inflammation as compared to the SS group. Serum levels of eotaxin were significantly elevated in the carboxylated MWCNT aspirated mice 1 day post exposure. Oropharyngeal aspiration of all three forms of MWCNTs resulted in a time and/or dose-dependent exacerbation of myocardial infarction. The severity of myocardial injury varied with the form of MWCNTs used. The N-doped MWCNT produced the greatest expansion of the infarct at any time point and required a log concentration lower to establish a no effect level. The expansion of the I/R injury remained significantly elevated at 28 days following aspiration of the COOH and N-doped forms, but not the C-grade as compared to SS.

Conclusion
Our results suggest that oropharyngeal aspiration of MWCNT promotes increased susceptibility of cardiac tissue to ischemia/reperfusion injury without a significant pulmonary inflammatory response. The cardiac injury effects were observed at low concentrations of MWCNTs and presence of MWCNTs may pose a significant risk to the cardiovascular system.
Surgical trial in traumatic intracerebral hemorrhage (STITCH(Trauma)): study protocol for a randomized controlled trial
Authors: Gregson Barbara A , Rowan Elise N , Mitchell Patrick M , Unterberg Andy , McColl Elaine M , Chambers Iain R , McNamee Paul , Mendelow A David 
Published: October 2012

Abstract

Background
Intracranial hemorrhage occurs in over 60% of severe head injuries in one of three types: extradural (EDH); subdural (SDH); and intraparenchymal (TICH). Prompt surgical removal of significant SDH and EDH is established and widely accepted. However, TICH is more common and is found in more than 40% of severe head injuries. It is associated with a worse outcome but the role for surgical removal remains undefined. Surgical practice in the treatment of TICHs differs widely around the world. The aim of early surgery in TICH removal is to prevent secondary brain injury. There have been trials of surgery for spontaneous ICH (including the STICH II trial), but none so far of surgery for TICH.

Methods/Design
The UK National Institutes of Health Research has funded STITCH(Trauma) to determine whether a policy of early surgery in patients with TICH improves outcome compared to a policy of initial conservative treatment. It will include a health economics component and carry out a subgroup analysis of patients undergoing invasive monitoring. This is an international multicenter pragmatic randomized controlled trial.
Patients are eligible if: they are within 48 h of injury; they have evidence of TICH on CT scan with a confluent volume of attenuation significantly raised above that of the background white and grey matter that has a total volume >10 mL; and their treating neurosurgeon is in equipoise.
Patients will be ineligible if they have: a significant surface hematoma (EDH or SDH) requiring surgery; a hemorrhage/contusion located in the cerebellum; three or more separate hematomas fulfilling inclusion criteria; or severe pre-existing physical or mental disability or severe co-morbidity which would lead to poor outcome even if the patient made a full recovery from the head injury.
Patients will be randomized via an independent service. Patients randomized to surgery receive surgery within 12 h. Both groups will be monitored according to standard neurosurgical practice. All patients have a CT scan at 5 days (+/−2 days) to assess changes in hematoma size. Follow-up is by postal questionnaire at 6 and 12 months. The recruitment target is 840 patients.

Trial registration
Current Controlled Trials ISRCTN19321911
Histotype-specific copy-number alterations in ovarian cancer
Authors: Huang Ruby YunJu , Chen Geng Bo , Matsumura Noriomi , Lai Hung-Cheng , Mori Seiichi , Li Jingjing , Wong Meng Kang , Konishi Ikuo , Thiery Jean-Paul , Goh Liang 
Published: October 2012

Abstract

Background
Epithelial ovarian cancer is characterized by multiple genomic alterations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and can be broadly categorized into 4 main histotypes of clear cell, endometrioid, mucinous, and serous. To date, histotype-specific copy number alterations have been difficult to elucidate. The difficulty lies in having sufficient sample size in each histotype for statistical analyses.

Methods
To dissect the heterogeneity of ovarian cancer and identify histotype-specific alterations, we used an in silico hypothesis-driven approach on multiple datasets of epithelial ovarian cancer.

Results
In concordance with previous studies on global copy number alterations landscape, the study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here significant histotype-specific copy number alterations in ovarian cancer and showed that there is genomic diversity amongst the histotypes. 76 cancer genes were found to be significantly altered with several as potential copy number drivers, including ERBB2 in mucinous, and TPM3 in endometrioid histotypes. ERBB2 was found to have preferential alterations, where it was amplified in mucinous (28.6%) but deleted in serous tumors (15.1%). Validation of ERBB2 expression showed significant correlation with microarray data (p=0.007). There also appeared to be reciprocal relationship between KRAS mutation and copy number alterations. In mucinous tumors where KRAS mutation is common, the gene was not significantly altered. However, KRAS was significantly amplified in serous tumors where mutations are rare in high grade tumors.

Conclusions
The study demonstrates that the copy number landscape is specific to the histotypes and identification of these alterations can pave the way for targeted drug therapy specific to the histotypes.
Child- and family impacts of infants’ oral conditions in Tanzania and Uganda– a cross sectional study
Authors: Masumo Ray , Bardsen Asgeir , Mashoto Kijakazi , Åstrøm Anne Nordrehaug 
Published: October 2012

Abstract

Background
Early childhood dental caries impacts on the quality of life of children and their families. This study set out to assess the psychometric properties of an oral health related quality of life, OHRQoL, measure, based on items emanating from the Child-and Family impact sections of the Early Childhood Oral Health Impact Scale (ECOHIS), in Kiswahili and Luganda speaking communities. It was hypothesized that the Child- and Family impact scores would discriminate between children with and without clinically defined dental problems and reported good and bad oral health.

Method
Kiswahili and Luganda versions of the Child- and Family impact scores were derived through translation in pilot studies. Totals of 1221 and 816 child/caretaker pairs attending health care facilities in Manyara, Tanzania and Kampala, Uganda, were recruited into the study. After caretakers completed the interview, their children underwent oral clinical examination.

Results
Internal consistency reliability (Cronbach’s alpha) was > 0.80 with respect to the Child impact score and 0.79 regarding the Family impact score. Multiple variable logistic- and Poisson regression analyses revealed that the Kiswahili and Luganda versions of the Child- and Family impact score associated in the expected direction with child’s oral diseases as with their reported health and oral health status. In Manyara, multiple logistic regression revealed that the ORs of reporting Child impacts were 1.8 (95% CI 1.0-3.4) and 2.2 (1.3-3.4) among caretakers who confirmed linear hypoplasia and teething symptoms, respectively. In Kampala, the ORs for reporting Child impacts were 2.3 (95% CI 1.3-3.9), 1.7 (95% CI 1.1-2.5), 1.6 (95% CI 1.2-2.3) and 2.7 (95% CI 1.3-5.8) among those who confirmed teeth present, hypoplasia, teething symptoms and tooth bud extractions, respectively. The odds ratios for reporting Family impacts were 2.7 (95% CI 1.5-4.7), 1.5 (95% CI 1.1- 2.1) and 4.6 (95% CI 2.0-10.7) if reporting LEH, teething symptoms and toothbud experience, respectively.

Conclusion
The Child and Family impact scores demonstrated acceptable internal consistency reliability and reproducibility whereas the discriminative validity was more ambiguous. The OHRQoL scores should be developed further and tested among Kiswahili and Luganda speaking caretakers.
Evaluation of recurrent hyphema after trabeculectomy with ultrabiomicroscopy 50-80 MHz: a case report
Authors: Mannino Giuseppe , Verrilli Sara , Calafiore Silvia , Ciarnella Angela , Cutini Alessandro , Mannino Cristina , Perdicchi Andrea , Recupero Santi Maria 
Published: October 2012

Abstract

Background
Hyphema is a complication that can occur after glaucoma filtering surgery. Biomicroscopic examination of the anterior segment is commonly used to diagnose it and gonioscopy may provide a useful support to find the source of the haemorrhage. Unfortunately, when the blood hides the structure of the anterior segment the gonioscopic examination fails. In this case we performed ultrabiomiscroscopy with 50–80 MHz probes to overcome the limits of gonioscopy. The use of this technique to study the anterior segment of the eye has previously been reported in literature, but we illustrates its importance for performing a correct diagnosis in a specific case of hyphema.

Case presentation
We report a case of a sixty-year-old caucasian male with recurrent hyphema in the left eye. The episodes of hyphema were four in two years and the patient came to the hospital for the first time in the last occasion. The past episodes were managed with topical corticosteroids and mydriatic drops. He referred surgical trabeculectomy in both eyes 5 years before the first symptoms and no specific eye trauma before the first episode. The examination of the anterior segment revealed a 2 mm hyphema in the left eye due to blood leakage through the superior iridectomy. Gonioscopy could not identify the source of the haemorrhage. B-scan ultrasound and ultrabiomiscroscopy, with 50–80 MHz probes, were performed. Ultrabiomiscroscopy, mainly with the probe of 80 MHz, provided images of high resolution of the structures of the anterior segment and it allowed the visualization of an abnormal vessel at the inner margin of the trabeculectomy opening, probably responsible of the recurrent hyphema.

Conclusion
Ultrabiomicroscopy proved to be a useful diagnostic technique for identifying the cause of the recurrent hyphema when other examination techniques are not applicable.
Glycodelin A is a prognostic marker to predict poor outcome in advanced stage ovarian cancer patients
Authors: Scholz Christoph , Heublein Sabine , Lenhard Miriam , Friese Klaus , Mayr Doris , Jeschke Udo 
Published: October 2012

Abstract

Background
Glycodelin is a cell surface glycoprotein offering a unique gender specific carbohydrate configuration. Sialylated carbohydrate structures, which are unusual for mammals, characterize Glycodelin isolated from amniotic fluid (Glycodelin A, GdA). Glycodelin in general exerts multiple, partly opposing functions ranging from immunosuppression to cell differentiation. As these markedly influence tumorigenesis, this study aimed to clarify whether expression of different Glycodelin isoforms is related to clinicopathological characteristics and prognosis of ovarian cancer patients. Further the use of Glycodelin as a serum marker in benign and malignant ovarian diseases was evaluated.

Methods
Ovarian cancer specimens (n = 152) were stained for Glycodelin with carbohydrate and peptide specific antibodies. Associations between Glycodelin expression and histological grading, FIGO stage as well as patient’s prognosis were examined. Glycodelin was correlated to expression of gonadotropin receptors and mucin-1, which are discussed as ovarian cancer tissue markers. In addition, Glycodelin serum concentrations were analyzed in patients suffering from benign (n = 73) or malignant (n = 38) ovarian neoplasias.

Results
Glycodelin A was found to be an independent prognostic marker for poor prognosis in advanced ovarian cancer patients. GdA staining correlated with gonadotropin receptor (FSHR and LHCGR) and with hCG expression. Gd expression showed a positive correlation with a tumour-associated epitope of mucin 1 (TA-MUC1). Further, compared to ovarian cancer, serum Gd was increased in patients with benign ovarian tumors.

Conclusion
Glycodelin A might be related to tumor aggressiveness and poor clinical outcome in advanced epithelial ovarian cancer. Glycodelin serum levels found in patients suffering from benign ovarian tumors, might contribute to a more global attenuation during progression of these precursor lesions.
Sulforaphane has opposing effects on TNF-alpha stimulated and unstimulated synoviocytes
Authors: Fragoulis Athanassios , Laufs Jendrik , Müller Susanna , Soppa Ulf , Siegl Stephanie , Reiss Lucy Kathleen , Tohidnezhad Mersedeh , Rosen Christian , Tenbrock Klaus , Varoga Deike , Lippross Sebastian , Pufe Thomas , Wruck Christoph Jan 
Published: October 2012

Abstract
Introduction
Rheumatoid arthritis (RA) is characterized by progressive inflammation associated with rampantly proliferating synoviocytes and joint destruction due to oxidative stress. Recently, we described nuclear factor erythroid 2-related factor 2 (Nrf2) as a major requirement for limiting cartilage destruction. NF-κB and AP-1 are the main transcription factors triggering the inflammatory progression in RA. We used sulforaphane, an isothiocyanate, which is both an Nrf2 inducer and a NF-κB and AP-1 inhibitor.

Methods
Cultured synoviocytes were stimulated with sulforaphane (SFN) with or without TNF-α pre-treatment. NF-κB, AP-1, and Nrf2 activation was investigated via dual luciferase reporter gene assays. Matrix metalloproteinases (MMPs) were measured via zymography and luminex technique. Cytokine levels were detected using ELISA. Cell viability, apoptosis and caspase activity were studied. Cell proliferation was analysed by real-time cell analysis.

Results
SFN treatment decreased inflammation and proliferation dose-dependently in TNF-α-stimulated synoviocytes. SFN did not reduce MMP-3 and MMP-9 activity or expression significantly. Interestingly, we demonstrated that SFN has opposing effects on naïve and TNF-α-stimulated synoviocytes. In naïve cells, SFN activated the cytoprotective transcription factor Nrf2. In marked contrast to this, SFN induced apoptosis in TNF-α-pre-stimulated synoviocytes.

Conclusions
We were able to show that SFN treatment acts contrary on naïve and inflammatory synoviocytes. SFN induces the cytoprotective transcription factor Nrf2 in naïve synoviocytes, whereas it induces apoptosis in inflamed synoviocytes. These findings indicate that the use of sulforaphane might be considered as an adjunctive therapeutic strategy to combat inflammation, pannus formation, and cartilage destruction in RA.
Parent-Reported Social Outcomes After Treatment for Pediatric Embryonal Tumors: A Prospective Longitudinal Study
Authors: Brinkman Tara M. , Palmer Shawna L. , Chen Si , Zhang Hui , Evankovich Karen , Swain Michelle A. , Bonner Melanie J. , Janzen Laura , Knight Sarah , Armstrong Carol L. , Boyle Robyn , Gajjar Amar 
Published: October 2012

Purpose To examine longitudinal parent-reported social outcomes for children treated for pediatric embryonal brain tumors. Patients and Methods Patients (N = 220) were enrolled onto a multisite clinical treatment protocol. Parents completed the Child Behavior Checklist/6-18 at the time of their child's diagnosis and yearly thereafter. A generalized linear mixed effects model regression approach was used to examine longitudinal changes in parent ratings of social competence, social problems, and withdrawn/depressed behaviors with demographic and treatment factors as covariates. Results During the 5-year period following diagnosis and treatment, few patients were reported to have clinically elevated scores on measures of social functioning. Mean scores differed significantly from population norms, yet remained within the average range. Several factors associated with unfavorable patterns of change in social functioning were identified. Patients with high-risk treatment status had a greater increase in parent-reported social problems (P = .001) and withdrawn/depressed behaviors (P = .01) over time compared with average-risk patients. Patients with posterior fossa syndrome had greater parent-reported social problems over time (P = .03). Female patients showed higher withdrawn/depressed scores over time compared with male patients (P < .001). Patient intelligence, age at diagnosis, and parent education level also contributed to parent report of social functioning. Conclusion Results of this study largely suggest positive social adjustment several years after diagnosis and treatment of a pediatric embryonal tumor. However, several factors, including treatment risk status and posterior fossa syndrome, may be important precursors of long-term social outcomes. Future research is needed to elucidate the trajectory of social functioning as these patients transition into adulthood.
Adjuvant Procarbazine, Lomustine, and Vincristine Chemotherapy in Newly Diagnosed Anaplastic Oligodendroglioma: Long-Term Follow-Up of EORTC Brain Tumor Group Study 26951
Authors: van den Bent Martin J. , Brandes Alba A. , Taphoorn Martin J.B. , Kros Johan M. , Kouwenhoven Mathilde C.M. , Delattre Jean-Yves , Bernsen Hans J.J.A. , Frenay Marc , Tijssen Cees C. , Grisold Wolfgang , Sipos László , Enting Roelien H. , French Pim J. , Dinjens Winand N.M. , Vecht Charles J. , Allgeier Anouk , Lacombe Denis , Gorlia Thierry , Hoang-Xuan Khê 
Published: October 2012

Purpose Anaplastic oligodendroglioma are chemotherapy-sensitive tumors. We now present the long-term follow-up findings of a randomized phase III study on the addition of six cycles of procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiotherapy (RT). Patients and Methods Adult patients with newly diagnosed anaplastic oligodendroglial tumors were randomly assigned to either 59.4 Gy of RT or the same RT followed by six cycles of adjuvant PCV. An exploratory analysis of the correlation between 1p/19q status and survival was part of the study. Retrospectively, the methylation status of the methyl-guanine methyl transferase gene promoter and the mutational status of the isocitrate dehydrogenase (IDH) gene were determined. The primary end points were overall survival (OS) and progression-free survival based on intent-to-treat analysis. Results A total of 368 patients were enrolled. With a median follow-up of 140 months, OS in the RT/PCV arm was significantly longer (42.3 v 30.6 months in the RT arm, hazard ratio [HR], 0.75; 95% CI, 0.60 to 0.95). In the 80 patients with a 1p/19q codeletion, OS was increased, with a trend toward more benefit from adjuvant PCV (OS not reached in the RT/PCV group v 112 months in the RT group; HR, 0.56; 95% CI, 0.31 to 1.03). IDH mutational status was also of prognostic significance. Conclusion The addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors. 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non–1p/19q-deleted tumors.
Single-Cell Analyses Reveal That KISS1R-Expressing Cells Undergo Sustained Kisspeptin-Induced Signaling That Is Dependent upon An Influx of Extracellular Ca2+
Authors: Babwah Andy V. , Pampillo Macarena , Min Le , Kaiser Ursula B. , Bhattacharya Moshmi 
Published: October 2012

Abstract
The kisspeptin receptor (KISS1R) is a Gαq/11-coupled seven-transmembrane receptor activated by a group of peptides referred to as kisspeptins (Kps). The Kp/KISS1R signaling system is a powerful regulator of GnRH secretion, and inactivating mutations in this system are associated with hypogonadotropic hypogonadism. A recent study revealed that Kp triggers prolonged signaling; not from the inability of the receptor to undergo rapid desensitization, but instead from the maintenance of a dynamic and active pool of KISS1R at the cell surface. To investigate this further, we hypothesized that if a dynamic pool of receptor is maintained at the cell surface for a protracted period, chronic Kp-10 treatment would trigger the sustained activation of Gαq/11 as evidenced through the prolonged activation of phospholipase C, protein kinase C, and prolonged mobilization of intracellular Ca2+. Through single-cell analyses, we tested our hypothesis in human embryonic kidney (HEK) 293 cells and found that was indeed the case. We subsequently determined that prolonged KISS1R signaling was not a phenomenon specific to HEK 293 cells but is likely a conserved property of KISS1R-expressing cells because evidence of sustained KISS1R signaling was also observed in the GT1–7 GnRH neuronal and Chinese hamster ovary cell lines. While exploring the regulation of prolonged KISS1R signaling, we identified a critical role for extracellular Ca2+. We found that although free intracellular Ca2+, primarily derived from intracellular stores, was sufficient to trigger the acute activation of a major KISS1R secondary effector, protein kinase C, it was insufficient to sustain chronic KISS1R signaling; instead extracellular Ca2+ was absolutely required for this.