bluuebunny/crossref_metadata_2025 huggingface dataset:
A Tumorigenic MLL-Homeobox Network in Human Glioblastoma Stem Cells
Authors: Gallo Marco , Ho Jenny , Coutinho Fiona J. , Vanner Robert , Lee Lilian , Head Renee , Ling Erick K. M. , Clarke Ian D. , Dirks Peter B.
Published: October 2012

Glioblastoma growth is driven by cancer cells that have stem cell properties, but molecular determinants of their tumorigenic behavior are poorly defined. In cancer, altered activity of the epigenetic modifiers Polycomb and Trithorax complexes may contribute to the neoplastic phenotype. Here, we provide the first mechanistic insights into the role of the Trithorax protein mixed lineage leukemia (MLL) in maintaining cancer stem cell characteristics in human glioblastoma. We found that MLL directly activates the Homeobox gene HOXA10. In turn, HOXA10 activates a downstream Homeobox network and other genes previously characterized for their role in tumorigenesis. The MLL–Homeobox axis we identified significantly contributes to the tumorigenic potential of glioblastoma stem cells. Our studies suggest a role for MLL in contributing to the epigenetic heterogeneity between tumor-initiating and non–tumor-initiating cells in glioblastoma. Cancer Res; 73(1); 417–27. ©2012 AACR.
Treatment Strategy for Superficial Pharyngeal Squamous Cell Carcinoma Synchronously Combined with Esophageal Cancer
Authors: Kaneko Kazuhiro , Yano Tomonori , Minashi Keiko , Kojima Takashi , Ito Miki , Satake Hironaga , Yajima Yoko , Yoda Yusuke , Ikematsu Hiroaki , Oono Yasuhiro , Hayashi Ryuichi , Onozawa Masakatsu , Ohtsu Atsushi
Published: October 2012

Background: Esophageal squamous cell carcinoma (ESCC) is often synchronously accompanied by pharyngeal squamous cell carcinoma (PSCC). However, treatment strategies for these synchronous cancers have not been established. Aim: To evaluate retrospectively the effects of both chemoradiotherapy (CRT) targeted for invasive ESCC on synchronous superficial PSCC and additional endoscopic resection (ER) for PSCC. Patients and Methods: Screening endoscopy in the pharynx was performed in newly diagnosed ESCC patients. CRT combined with 5-fluorouracil (5-FU) and cisplatin (CDDP) was administered to all patients. The effect on superficial PSCC was only evaluated for 5-FU-CDDP chemotherapy that excluded the pharynx from the radiation field. When PSCC was remnant or recurrent in patients evaluated at complete response (CR) of ESCC, ER was performed on the PSCC. Results: Fourteen cases of superficial PSCC (4.0%) were detected in 348 ESCC patients. Three PSCC reached CR in 8 ESCC-CR patients, while all 3 lesions recurred. No treatment response was found in the remaining 11 PSCC. As a second treatment, ER for 8 PSCC was completed in the 8 ESCC-CR patients, with one complication due to pneumonia. Conclusions: Standard 5-FU-CDDP CRT targeted for invasive ESCC did not demonstrate a sufficient efficacy for superficial PSCC, while ER even for PSCC after chemotherapy was curative.
Prevalence, Treatment and Control of Hypertension in a Croatian Endemic Nephropathy Area
Authors: Dika Živka , Juras Josip , Kos Jelena , Edwards Karen , Fištrek Margareta , Premužić Vedran , Laganović Mario , Abramović-Baríc Mirta , Cvitković Ante , Vuković Lela Ivana , Karanović Sandra , Jurić Dragana , Bitunjac Milan , Teskera Tomislav , Jelaković Bojan
Published: October 2012

Background: Hypertension is not considered to be a characteristic of endemic nephropathy (EN). Recent observations suggested that it might be more prevalent than it was reported before. Aim: The aim of our study was to analyze prevalence, treatment and control of hypertension in a Croatian endemic area. Methods: In the present cross-sectional study, 1,602 farmers were enrolled, 1,246 from EN and 356 from control villages. Epidemiological and medical histories were taken and clinical and laboratory examinations performed for kidney function. Blood pressure was measured following the ESH/ESC guidelines. Results: The prevalence of hypertension in EN villages was higher than in control (50.8 vs. 46.5%, p = 0.005). There was no difference in overall treatment, control of all and treated hypertensives between the villages. In all villages, women were treated more than men (EN 41.6 vs. 28.4%, p < 0.001; control 46.4 vs. 27.3%, p < 0.001), but better control of treated was achieved in men (EN 24.7 vs. 17.4%, p = 0.002; control 29.6 vs. 15.5%, p = 0.002). Women had lower income and level of education than men (p < 0.01). Conclusion: Hypertension is highly prevalent in endemic villages. In all villages, men had better blood pressure control despite being treated less. This finding could be explained by poorer education and income in women.
Changing Profile of 7,519 Neurologic Outpatients Evaluated over 20 Years
Authors: Del Brutto Victor J. , Tettamanti Daniel , Del Brutto Oscar H.
Published: October 2012

Introduction: There is scarce information on the demographic profile and diseases affecting neurologic outpatients. Methods: We evaluated 7,519 neurologic outpatients over 20 years at the outpatient clinic of the Department of Neurological Sciences, Hospital-Clínica Kennedy, Guayaquil, Ecuador. Results: Mean age was 48 ± 19.4 years, and 57.8% were women. Common reasons for consultation included headache (33.2%), focal deficits (10.7%), and seizures (9%). The most common categories of neurologic diseases were cerebrovascular (10.6%), degenerative (7.6%), and traumatic (7.1%). Diseases of uncertain/unknown etiology accounted for 50.2% of cases. Young patients were most often evaluated for headache and seizures, while elderly patients usually presented with focal deficits, movement disorders, or cognitive decline. We also found significant variations in the prevalence of neurologic diseases over the study years. While the prevalence of degenerative diseases increased from 5.7% in 1990–1994 to 10.2% in 2005–2009, that of infectious diseases steadily decreased from 3.7 to 2.1% over the study years. Conclusion: There was a dynamic pattern of neurologic diseases over the years. Nowadays, distribution of neurologic symptoms and diseases in our population is more similar to that reported from the developed world than it was 20 years ago.
TNF-Dependent Signaling Pathways in Liver Cancer: Promising Targets for Therapeutic Strategies?
Authors: Roderburg Christoph , Gautheron Jeremie , Luedde Tom
Published: October 2012

Liver cancer represents a growing health burden worldwide, and treatment options are still limited. Hepatocellular carcinoma (HCC), the most frequent primary hepatic malignancy, arises in most instances in chronically inflamed and fibrotic livers. However, current systemic molecular therapies against HCC are mainly focusing on tyrosine kinases involved in angiogenic and oncogenic signaling pathways, whereas the knowledge on the unique association between inflammation and carcinogenesis in the liver has not yet translated into preventive or therapeutic concepts against HCC. Tumor necrosis factor (TNF) is a cytokine derived from monocytes and various other immunological and parenchymal cells. Upon binding to its receptors, TNF activates different signaling cascades including the pro-apoptotic caspase cascade as well as inflammatory and stress-related pathways such as the NF-ĸB, p38MAPK, and Jun-(N)-terminal kinase (JNK) pathways. The role of TNF in cancer is controversial, since it was attributed both pro- and anti-carcinogenic functions. Its potential function in hepatocarcinogenesis has lately been investigated using genetically modified mouse models. These studies have highlighted that the various TNF-dependent signaling pathways withhold distinct functions in hepatocarcinogenesis, which are in part controversial and strongly depend on the experimental model system. Nevertheless, careful interpretation of findings in mouse models and critical consideration of their limitations might result in a new understanding of this complex pathway in hepatocarcinogenesis and thus might help identify the most promising targets in the TNF pathway and the appropriate clinical settings for future chemo-preventive or therapeutic strategies against HCC.
Tissue Composition of the Vaginal Wall in Women with Pelvic Organ Prolapse
Authors: Meijerink Aukje M. , van Rijssel Reinier H. , van der Linden Paul J.Q.
Published: October 2012

Background/Aims: To determine the composition of the vaginal wall and to explore the connective tissue layer, muscularis and basement membrane in relation to the pathogenesis of pelvic organ prolapse (POP). Methods: We performed a histopathological study with respect to the composition of the vaginal wall of 33 patients and 9 controls. Tissue samples from the vaginal wall were analysed for collagens II and IV, desmin, elastin, fibronectin, smooth muscle actin (SMA) and transforming growth factor (TGF)-β1 using (immuno)histochemistry. Morphometric analyses were also performed. Results: Morphometric characteristics and expression of SMA, TGF-β1, elastin and collagen II were significantly altered in women with POP. Conclusion: Our results suggest that there could be an altered tissue composition of the vaginal wall in women with POP. SMA expression could play a role in the pathogenesis of POP. The alterations in elastin and TGF-β1 expression are likely a result of POP.
Psoriasis Comorbidities: Results from the National Psoriasis Foundation Surveys 2003 to 2011
Authors: Armstrong April W. , Schupp Clayton , Bebo Bruce
Published: October 2012

Background: Studies examining comorbidities among psoriasis patients with varying disease severities measured by body surface area (BSA) are lacking. Objective: To examine the association between psoriasis severity and comorbid conditions, including rheumatologic, cardiovascular and other immune-mediated diseases. Methods: From 2003 to 2011, the National Psoriasis Foundation conducted surveys among 5,604 psoriasis patients. The combined surveys represented the largest study to date that used BSA as a direct measure of psoriasis severity for comorbidity assessment. Results: Over 86% of psoriatic arthritis (PsA) patients reported presenting with psoriasis prior to PsA; the diagnosis of psoriasis preceded that of PsA by a mean period of 14.6 years. Compared to those with mild psoriasis, patients with moderate-to-severe psoriasis had significantly increased adjusted odds of PsA (moderate: odds ratio, OR: 1.21, 95% confidence interval, CI: 1.04–1.41; severe: OR: 2.32, 95% CI: 1.98–2.70). Patients with severe psoriasis had increased adjusted odds of diabetes (OR: 1.5, 95% CI: 1.08–2.08) and cardiovascular disease (OR: 1.5, 95% CI: 1.01–2.24) compared to those with mild-to-moderate psoriasis. Odds of rheumatoid arthritis, ankylosing spondylitis, lupus, Crohn’s disease and multiple sclerosis were not significantly increased in patients with severe psoriasis. Conclusion: Compared to those with mild-to-moderate psoriasis, patients with severe psoriasis are at increased odds of PsA, diabetes and cardiovascular diseases.
Age-Related Aspects of Cutaneous Wound Healing: A Mini-Review
Authors: Sgonc Roswitha , Gruber Johann
Published: October 2012

As the aging population in developed countries is growing in both numbers and percentage, the medical, social, and economic burdens posed by nonhealing wounds are increasing. Hence, it is all the more important to understand the mechanisms underlying age-related impairments in wound healing. The purpose of this article is to give a concise overview of (1) normal wound healing, (2) alterations in aging skin that have an impact on wound repair, (3) alterations in the repair process of aged skin, and (4) general factors associated with old age that might impair wound healing, with a focus on the literature of the last 10 years.
Inherent Grading Characteristics of Individual Pathologists Contribute to Clinically and Prognostically Relevant Interobserver Discordance Concerning Broders' Grading of Penile Squamous Cell Carcinomas
Authors: Gunia Sven , Burger Maximilian , Hakenberg Oliver W. , May Dieter , Koch Stefan , Jain Anjun , Birnkammer Kristina , Wieland Wolf F. , Otto Wolfgang , Hofstädter Ferdinand , Fritsche Hans-Martin , Denzinger Stefan , Gilfrich Christian , Brookman-May Sabine , May Matthias
Published: October 2012

Introduction: We assessed the reproducibility and prognostic impact of the Broders' grading system (BGS) in a cohort of 147 patients with surgically treated penile squamous cell carcinomas. Materials and Methods: Conventionally stained histology slides were graded according to the BGS in two rounds by two study pathologists. Reproducibility was assessed using ĸ statistics. Multivariable analyses were calculated to predict cancer-specific survival (CSS). The ‘mean grade' per pathologist per round was calculated by allocating grade points to each study case (G1-G4: 1-4 points) and dividing the sum of all grade points by the number of cases examined. Results: The BGS showed substantial interobserver variation (59-87% with ĸ = 0.38-0.69) but almost perfect intraobserver reproducibility (91% with ĸ = 0.86 and 96% with ĸ = 0.94, respectively). The ‘mean grade' per pathologist remained nearly constant in both rounds of examination (differences ≤0.05 grade points) but differed between the two pathologists (up to 0.4 grade points). In multivariable analyses, the prognostic impact of the BGS in terms of CSS was strongly pathologist-dependent. Conclusions: Clinically and prognostically relevant interobserver discordance concerning the BGS seems, at least in part, to be attributable to inherent ‘aggressive' versus ‘reserved' grading characteristics of individual pathologists.
A Natural Tetrahydropyrimidine, Ectoine, Ameliorates Ischemia Reperfusion Injury after Intestinal Transplantation in Rats
Authors: Pech Thomas , Ohsawa Ichiro , Praktiknjo Michael , Overhaus Marcus , Wehner Sven , von Websky Martin , Abu-Elmagd Kareem , van Echten-Deckert Gerhild , Kalff Joerg C. , Schaefer Nico
Published: October 2012

Background/Aims: Ischemia reperfusion (I/R) injury after small bowel transplantation leads to inflammatory reactions and loss of structural integrity with subsequent graft contractile dysfunction in the early postoperative phase. The natural tetrahydropyrimidine ectoine (1-,4-,5-,6-tetrahydro-2-methyl-4-pyrimidine carboxylic acid; THP) protects the ileal mucosa and muscularis against effects of I/R injury in an experimental model of isolated graft reperfusion. The effects of THP treatment were evaluated in an established experimental intestinal transplant model. Methods: Isogenic, orthotopic small bowel transplantation was performed in Lewis rats (6 h cold ischemia time). Perioperative THP treatment (intraluminal/intravascular) groups were compared to vehicle-treated animals (after 3 and 24 h) and non-transplanted controls (n = 5/group). Park’s score defined the effects of I/R injury. The infiltration of neutrophils, monocytes and macrophages, mRNA expression of IL-6 and TNF-α, serum levels of IL-6 and NO and smooth muscle contractility were evaluated. Results: Improved graft outcome after intraluminal and intravascular THP treatment was defined by considerably ameliorated neutrophil infiltration and less histological signs of I/R injury (p ≤ 0.05). In the presence of THP, mRNA expression of IL-6 and TNF-α and IL-6 and NO serum levels were reduced and smooth muscle function was improved. Conclusion: THP treatment offers protection against the effects of I/R injury in intestinal transplantation in vivo, however, only as supplementary treatment option.
Retinoids Augment the Expression of Podocyte Proteins by Glomerular Parietal Epithelial Cells in Experimental Glomerular Disease
Authors: Zhang Jiong , Pippin Jeffrey W. , Vaughan Michael R. , Krofft Ronald D. , Taniguchi Yoshinori , Romagnani Paola , Nelson Peter J. , Liu Zhi-Hong , Shankland Stuart J.
Published: October 2012

Background/Aims: A decrease in glomerular podocyte number in membranous nephropathy and focal segmental glomerulosclerosis (FSGS) ultimately underlines glomerulosclerosis and the decrease in kidney function. Recent studies have shown that in these diseases, glomerular parietal epithelial cells begin to express proteins considered unique to podocytes, and that these glomerular epithelial transition cells might serve as podocyte progenitors. Because retinoids improve many forms of experimental glomerular disease characterized by podocyte injury and loss, we asked if all-trans retinoic acid (ATRA) induces parietal epithelial cells to express podocyte proteins. Methods: ATRA or vehicle was administered to rats with experimental membranous nephropathy (passive Heymann nephritis model) and mice with experimental FSGS (anti-glomerular antibody model) following the onset of proteinuria. Immunohistochemistry staining of PAX2 (parietal epithelial cell marker), WT-1 (podocyte cell marker), and Ki-67 (proliferation marker) were performed on kidney tissues. Results: Compared to diseased animals receiving vehicle, ATRA statistically significantly increased the number of glomerular transition cells, defined as cells double-staining for PAX2 and WT-1, in membranous nephropathy at weeks 2, 5 and 16, and in FSGS at weeks 1 and 2. This was accompanied by an increase in the number of podocytes compared to diseased controls receiving vehicle. Conclusion: ATRA increases the number of glomerular epithelial transition cells in experimental proteinuric glomerular diseases. Thus, ATRA may provide a useful pharmacologic approach to decipher the mechanisms underlying the possible progenitor role of parietal epithelial cells.
Mammalian Target of Rapamycin as a Rational Therapeutic Target for Breast Cancer Treatment
Authors: LoRusso Patricia Mucci
Published: October 2012

Therapies directed at endocrine receptors and human epidermal growth factor receptor 2 are important treatment options for patients with breast cancer; however, drug resistance and subsequent disease progression in patients with advanced disease is inevitable. The mammalian target of rapamycin (mTOR) is a key regulator of cell growth and proliferation implicated in the cellular processes that lead to the uncontrolled growth of cancer cells. Hence, overactivation of the mTOR pathway may also represent a key process in the development of resistance to these therapies, and interrupting this signaling cascade may alleviate resistance and help restore drug sensitivity. A number of agents that target the mTOR pathway have shown potent antitumorigenic effects in vitro, and several agents have also shown promise in treating patients with breast cancer. Everolimus and temsirolimus are the most clinically advanced agents in this class, with recent data from the BOLERO-2 study indicating significant benefit associated with everolimus when added to endocrine therapy in patients with endocrine therapy-resistant disease. In this review, we consider the translation of mTOR inhibitors from laboratory studies to large clinical trials, driven by a rational understanding of the role of mTOR in the processes that underlie breast cancer tumorigenesis.
Fluidics in a Dual Pneumatic Ultra High-Speed Vitreous Cutter System
Authors: Diniz Bruno , Ribeiro Ramiro M. , Fernandes Rodrigo B. , Lue Jaw-Chyng , Teixeira Anderson G. , Maia Mauricio , Humayun Mark S.
Published: October 2012

Background: Dual pneumatic systems use two separate air line tubes to open and close the cutter and can achieve high cut rates. The purpose of this study is to evaluate the influence of gauge size, cut rate and aspiration on the flow rate performance of ultra high-speed cutters operated with a commercially available dual pneumatic vitrectomy system. Methods: Analysis of a high-speed video was used to determine duty cycle. Flow rates from 20-, 23- and 25-gauge cutters were calculated in predetermined conditions of aspiration levels and cut rates; water and fresh porcine vitreous samples were studied. Results: For all three gauges of cutters, the duty cycle and water flow showed an inverse correlation with increasing cut rates and a direct correlation with increasing aspiration levels (p < 0.05). Vitreous flow rates from all gauges increased with increasing aspiration and cut rates (p < 0.05). Conclusion: Larger gauges of the cutters as well as higher aspiration and cut rate levels resulted in improvement of the vitreous flow rates. A good understanding of the different flow rate settings is essential for the surgeon and optimizes the safety of surgical procedures.
Obesity Interacts with Cerebral Hypoperfusion to Exacerbate Cognitive Impairment in Older Adults with Heart Failure
Authors: Alosco Michael L. , Spitznagel Mary Beth , Raz Naftali , Cohen Ronald , Sweet Lawrence H. , Colbert Lisa H. , Josephson Richard , van Dulmen Manfred , Hughes Joel , Rosneck Jim , Gunstad John
Published: October 2012

Background: Cerebral hypoperfusion accompanies heart failure (HF) and is associated with reduced cognitive performance. Obesity is prevalent in persons with HF and is also a likely contributor to cognitive function, as it has been independently linked to cognitive impairment in healthy individuals. The current study examined the association between obesity and cognitive performance among older adults with HF and whether obesity interacts with cerebral hypoperfusion to exacerbate cognitive impairment. Methods: Patients with HF (n = 99, 67.46 ± 11.36 years of age) completed neuropsychological testing and impedance cardiography. Cerebral blood flow velocity (CBF-V) measured by transcranial Doppler sonography quantified cerebral perfusion and body mass index (BMI) operationalized obesity. Results: A hierarchical regression analysis showed that lower CBF-V was associated with reduced performance on tests of attention/executive function and memory. Elevated BMI was independently associated with reduced attention/executive function and language test performance. Notably, a significant interaction between CBF-V and BMI indicated that a combination of hypoperfusion and high BMI has an especially adverse influence on attention/executive function in HF patients. Conclusions: The current findings suggest that cerebral hypoperfusion and obesity interact to impair cognitive performance in persons with HF. These results may have important clinical implications, as HF patients who are at high risk for cerebral hypoperfusion may benefit from weight reduction.
Effects of Different Suture Materials Used for the Repair of Hypospadias: A Stereological Study in a Rat Model
Authors: Shirazi Mehdi , Noorafshan Ali , Serhan Ali
Published: October 2012

Introduction: Repair of the penile urethra in hypospadias is done with different suture materials. The aim of this study was to quantify the impact of different suture threads on histological parameters of the penis and urethra following hypospadias repair in rats. Materials and Methods: Six groups of the rats, except for the control group, underwent incision and repair of the penis and urethra in the ventral line using different suture materials including Chromic, Vicryl (polyglactic acid), PDS (polydioxanone), Rapid Vicryl (polyglactin 910), Monocryl (poliglecaprone 25) and control groups. After 3 weeks the body of the penis was excised and histological sections were studied using stereological methods. Results: Monocryl (poliglecaprone 25) was associated with a higher percentage of vessel density, higher volume of urethral lumen and lower lymphocyte infiltration. Volume of urethral epithelium was highest in the PDS group compared to the other operated groups. There was no significant difference regarding collagen deposition and fibroblast infiltration among the operated groups. Conclusions: The Monocryl and PDS groups showed better results.
Response to Vitamin D3 Supplementation in Obese and Non-Obese Caucasian Adolescents
Authors: Aguirre Castaneda Roxana , Nader Nicole , Weaver Amy , Singh Ravinder , Kumar Seema
Published: October 2012

Background/Aims: Vitamin D deficiency is highly prevalent in obese children, and obese children tend to respond poorly to vitamin D supplementation. The objective of the study was to compare the response to vitamin D3 supplementation (2,000 IU once daily for 12 weeks) between obese and non-obese Caucasian adolescents. Methods: The study design was open label non-randomized. It was carried out at a single center. Eighteen obese adolescents (aged 12–18 years) and the same number of age-, gender- and season-matched non-obese adolescents received vitamin D3 (2,000 IU/day) orally for 12 weeks. Total serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone, calcium and phosphorus were measured at baseline and at the end of the 12-week period. Results: The mean baseline 25(OH)D level was higher in the non-obese compared to the obese subjects (mean 28.9 vs. 25.2 ng/ml; p = 0.029). The increment in 25(OH)D levels following vitamin D supplementation was significantly lower in the obese adolescents (mean change 5.8 vs. 9.8 ng/ml; p = 0.019). Conclusions: Higher doses of vitamin D are required to treat vitamin D deficiency in obese adolescents compared to their non-obese peers.
Loss of Penumbra by Impaired Oxygen Supply Decreasing Hemoglobin Levels Predict Infarct Growth after Acute Ischemic Stroke
Authors: Kellert L. , Herweh C. , Sykora M. , Gussmann P. , Martin E. , Ringleb P.A. , Steiner T. , Bösel J.
Published: October 2012

Background: The association of mortality and poor outcome with reduced levels of hemoglobin (Hb) and hematocrit (Hct) in patients admitted for ischemic stroke was recently demonstrated. The mechanisms behind this have remained unclear. Aims: Here, we aimed to investigate a putative association between low Hb and Hct levels and infarct growth. Methods: All consecutive patients who received intravenous thrombolysis based on multimodal magnetic resonance imaging during the years 1998–2009 were screened. Laboratory data as well as admission magnetic resonance images and follow-up computed tomography scans of 257 patients were assessed. Overall, data of 100 patients were of sufficient quality and further analyzed. Results: Decrease in Hb and Hct as well as perfusion-weighted imaging volume, mismatch volume, and final infarct size on follow-up computed tomography were associated with infarct growth. A linear regression model revealed Hb decrease (β = 0.23, p = 0.02) to be a predictor of infarct growth, independent of mismatch volume (β = 0.27, p = 0.004) and minimum sodium (β = -0.21, p = 0.03), and adjusted to the non-predicting variables age, National Institute of Health Stroke Scale score, maximum leucocytes and C-reactive protein, blood glucose, and Hct decrease. Conclusion: Hb levels that decrease after admission independently predict infarct growth in thrombolyzed stroke patients. The clinical implications of this relationship remain to be investigated.
Pressure Overload Regulates Expression of Cytokines, γH2AX, and Growth Arrest- and DNA-Damage Inducible Protein 153 via Glycogen Synthase Kinase-3β in Ischemic-Reperfused Hearts
Authors: Baban Babak , Liu Jun Yao , Mozaffari Mahmood S.
Published: October 2012

The growth arrest- and DNA-damage inducible protein 153 (GADD153) regulates both apoptosis and inflammatory response. Importantly, glycogen synthase kinase-3β (GSK-3β) may provide a mechanistic link for cellular expression of GADD153, inflammatory response, and cell death. We previously showed that pressure overload exacerbates myocardial ischemia reperfusion injury associated with significant reduction in phosphorylated (inactive) GSK-3β. This raises the possibility that pressure overload, through a GSK-3β-dependent mechanism, increases GADD153 expression, thereby upregulating inflammatory cytokine production and contributing to worsening of myocardial ischemia reperfusion injury. Accordingly, Langendorff-perfused rat hearts were subjected to global ischemia reperfusion protocol in the absence or presence of the GSK-3β inhibitor, lithium chloride (1 mmol/L), with perfusion pressure set at 80 or 160 cmH
2
O; normoxic hearts served as controls. Compared with normoxia, an ischemia reperfusion insult increased expressions of proinflammatory cytokines, γH2AX, and GADD153 in association with increased cell death. In the ischemic-reperfused hearts, pressure overload did the following: (1) reduced interleukin-10 but increased interleukin-17 (cardiomyocytes), without affecting interleukin-23; (2) increased expressions of γH2AX and GADD153; (3) decreased 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) aggregates but increased JC-1 monomers (suggestive of reduced mitochondrial membrane potential, ψ
m
); and (4) increased annexin V immunostaining as well as apoptotic and necrotic cell death. Treatment with lithium chloride caused a robust increase in interleukin-10, preserved ψ
m
, and markedly decreased all other parameters with the effect being most prominent for hearts perfused at the high pressure. In conclusion, pressure overload, via a GSK-3β-dependent mechanism, exacerbates cell death in the isolated ischemic-reperfused heart involving regulation of inflammatory response, DNA injury, and GADD153 expression.
Interferon-γ Signaling Inhibition Ameliorates Angiotensin II–Induced Cardiac Damage
Authors: Markó Lajos , Kvakan Heda , Park Joon-Keun , Qadri Fatimunnisa , Spallek Bastian , Binger Katrina J. , Bowman Edward P. , Kleinewietfeld Markus , Fokuhl Verena , Dechend Ralf , Müller Dominik N.
Published: October 2012

Angiotensin (Ang) II induces vascular injury in part by activating innate and adaptive immunity; however, the mechanisms are unclear. We investigated the role of interferon (IFN)-γ and interleukin (IL)-23 signaling. We infused Ang II into IFN-γ receptor (IFN-γR) knockout mice and wild-type controls, as well as into mice treated with neutralizing antibodies against IL-23 receptor and IL-17A. Ang II–treated IFN-γR knockout mice exhibited reduced cardiac hypertrophy, reduced cardiac macrophage and T-cell infiltration, less fibrosis, and less arrhythmogenic electric remodeling independent of blood pressure changes. In contrast, IL-23 receptor antibody treatment did not reduce cardiac hypertrophy, fibrosis, or electric remodeling despite mildly reduced inflammation. IL-17A antibody treatment behaved similarly. In the kidney, IFN-γR deficiency reduced inflammation and tubulointerstitial damage and improved glomerular filtration rate. Nonetheless, albuminuria was increased compared with Ang II–treated wild-type controls. The glomeruli of Ang II–treated IFN-γR knockout mice exhibited fewer podocytes, less nephrin and synaptopodin staining, and impaired podocyte autophagy. Thus, IFN-γ blockade, but not IL-23 receptor antibody treatment, protects from Ang II–induced cardiac damage and electric remodeling. In the kidney, IFN-γ signaling acts in a cell type–specific manner. Glomerular filtration rate is preserved in the absence of the IFN-γR, whereas podocytes may require the IFN-γR in the presence of Ang II for normal integrity and function.
Unraveling Life's Building Blocks: Sculpture Inspired by Proteins
Authors: Voss-Andreae Julian
Published: October 2012

Inspired by proteins, the molecular building blocks of life, the author's presented work re-creates the first step of the emergence of three-dimensional bodies from one-dimensional DNA. Utilizing an algorithmic approach as his point of departure, the artist follows his vision freely, creating sculptures that bring life's isolated components emotionally back to life. In this sequel to an earlier Leonardo article on the inception of his protein-inspired sculptures, the author presents the unfolding of his vision: Large-scale works of increasing formal and conceptual complexity display the emergence of an organic aesthetic from geometric elements and inspire a more holistic view of nature than that provided by reductionist science alone.
The Veiled Christ of Cappella Sansevero: On Art, Vision and Reality
Authors: Albright Thomas D.
Published: October 2012

A celebrated marble sculpture of the body of Jesus, known as Cristo Velato (Veiled Christ), by the 18th-century Neapolitan artist Giuseppe Sanmartino offers a dramatic demonstration of art as all-encompassing illusion. As such, Sanmartino's masterpiece provides a rare opportunity to deconstruct a multifaceted and richly deceptive perceptual experience into a collection of simple sensory elements. This analysis both yields insights into the visual tools of the artist and reveals how an empirical understanding of sensory processes can illuminate complex perceptual experiences.
Mobiles, Molecules and the Coalescence of Processes
Authors: Kawai Stephen H.
Published: October 2012

The author provides an account of his development and experiences as both a visual (mobile) artist and a chemist. He describes the surprising similarities between the planning of the construction of a mobile and the execution of retrosynthetic analysis used to chemically create a particular molecule. The fusion of these two independently initiated mental processes into a common creative act can be referred to as a coalescence of processes. The present article discusses the consequences of this merging for both artistic and scientific practices, as well as its relevance to the artscience concept of idea translation.
Dynamic Sites: Learning to Design in Techno-Social Landscapes
Authors: McMeel Dermott , Speed Chris
Published: October 2012

This paper investigates interdisciplinary research through an urban design project and explores the creation of broader architectural representations of place. It advances the case made by McCarthy and Wright for developing deeper associations between experience and technology. Drawing on artist Janet Cardiff's media representations of space, design students were challenged to represent richer descriptions of place that include factors such as temporal and spatial resistance, experiential laminations, and social linkages and their gaps. Findings support a view of design and transdisciplinarity as potentially compelling modalities for research in these complex contexts, discourage bringing technology to center stage and encourage propositions that recommend looking beyond the functional and attending to personal and social facets of our interaction with technology.
Relative Roles of Circumnavigating Waves and Extratropics on the MJO and Its Relationship with the Mean State*
Authors: Ray Pallav , Li Tim
Published: October 2012

A set of atmospheric general circulation model (GCM) experiments is designed to explore the relative roles of the circumnavigating waves and the extratropics on the Madden–Julian oscillation (MJO). In a “control” simulation, the model is forced by the climatological monthly sea surface temperature for 20 yr. In the first sensitivity experiment, model prognostic variables are relaxed in the tropical Atlantic region (20°S–20°N, 80°W–0°) toward the “controlled” climatological annual cycle to suppress the influences from the circumnavigating waves. In the second sensitivity experiment, model prognostic variables are relaxed in the 20°–30° latitude zones toward the controlled climatological annual cycle to suppress the influences from the extratropics (or the tropics–extratropics interactions). The numerical results demonstrate that the extratropics play a more important role in maintaining the MJO variance than the circumnavigating waves.

The simulations further show that both the tropical mean precipitation and the intraseasonal precipitation variability are reduced when the extratropical influences are suppressed. The in-phase relationship is primarily attributed to the effect of the mean state on perturbations. A moisture budget analysis indicates that a positive feedback to the mean precipitation by the anomalous moisture convergence is offset by a negative feedback due to the anomalous moisture advection. The change in the mean precipitation in the absence of extratropical influences is primarily determined by the change in the mean moisture convergence, which in turn is due to the change in circulation. This study is the first attempt to quantitatively separate the effects of the circumnavigating waves and the extratropics on the MJO. Implications and limitations of this study are discussed.
Groundwater Constraints on Simulated Transpiration Variability over Southeastern Australian Forests
Authors: Decker M. , Pitman A. J. , Evans J. P.
Published: October 2012

A land surface scheme with and without groundwater–vegetation interactions is used to explore the impact of rainfall variability on transpiration over drought-vulnerable regions of southeastern Australia. The authors demonstrate that if groundwater is included in the simulations, there is a low correlation between rainfall variability and the response of transpiration to this variability over forested regions. Groundwater reduces near-surface water variability, enabling forests to maintain transpiration through several years of low rainfall, in agreement with independent observations of vegetation greenness. If groundwater is not included, the transpiration variability matches the rainfall variability independent of land cover type. The authors’ results suggest that omitting groundwater in regions where groundwater sustains forests will 1) probably overestimate the likelihood of forest dieback during drought, 2) overestimate a positive feedback linked with declining transpiration and a drying boundary layer, and 3) underestimate the impact of land cover change due to inadequately simulating the different responses to drought for different land cover types.
Internal Wave Reflection on Shelf Slopes with Depth-Varying Stratification
Authors: Hall Rob A. , Huthnance John M. , Williams Richard G.
Published: October 2012

Reflection of internal waves from sloping topography is simple to predict for uniform stratification and linear slope gradients. However, depth-varying stratification presents the complication that regions of the slope may be subcritical and other regions supercritical. Here, a numerical model is used to simulate a mode-1, M2 internal tide approaching a shelf slope with both uniform and depth-varying stratifications. The fractions of incident internal wave energy reflected back offshore and transmitted onto the shelf are diagnosed by calculating the energy flux at the base of slope (with and without topography) and at the shelf break. For the stratifications/topographies considered in this study, the fraction of energy reflected for a given slope criticality is similar for both uniform and depth-varying stratifications. This suggests the fraction reflected is dependent only on maximum slope criticality and independent of the depth of the pycnocline. The majority of the reflected energy flux is in mode 1, with only minor contributions from higher modes due to topographic scattering. The fraction of energy transmitted is dependent on the depth-structure of the stratification and cannot be predicted from maximum slope criticality. If near-surface stratification is weak, transmitted internal waves may not reach the shelf break because of decreased horizontal wavelength and group velocity.
Contrast-Induced Nephropathy in Patients With ST Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention
Authors: Elbasan Zafer , Şahin Durmuş Yıldıray , Gür Mustafa , Kuloğlu Osman , Kıvrak Ali , İçen Yahya Kemal , Türkoğlu Caner , Yıldırım Arafat , Özdoğru İbrahim , Çaylı Murat
Published: October 2012

We assessed the relationship between contrast-induced nephropathy (CIN) and SYNTAX score (SS) and serum uric acid (SUA) levels in patients with ST elevation myocardial infarction (STEMI). A total of 835 STEMI patients in whom primary percutaneous coronary intervention was performed in our cardiology clinic were included in this study (615 male, 220 female; mean age 58.1 ± 12.2 years). The patients were divided into 2 groups (CIN and non-CIN). Contrast-induced nephropathy was observed in 9.6% (80) of patients; SS (13.9 ± 6.2/22.1 ± 5.8) and SUA (5.1 ± 0.9/6.2 ± 0.9) values in the CIN group were higher compared with the non-CIN group ( P < .001, for all). All SS (95% confidence interval [CI] = 1.136-1.250, P = .001), SUA (95% CI = 1.877-3.236, P = .002), and diabetes (95% CI = 0.998-1.039, P = .026) were independent predictors of CIN in logistic regression analysis. Procedures that can prevent CIN may be beneficial in patients at high risk as identified by the SS and SUA levels.
The Ethnicity–Policy Preference Link in Sub-Saharan Africa
Authors: Lieberman Evan S. , McClendon Gwyneth H.
Published: October 2012

Scholars have begun to investigate the mechanisms that link ethnic diversity to low levels of public goods provision but have paid only minimal attention to the role of preferences for public policies. Some argue that ethnic groups hold culturally distinctive preferences for goods and policies, and that such differences impede effective policy making, but these studies provide little evidence to support this claim. Others argue that preferences do not vary systematically across ethnic groups, but again the evidence is limited. In this article, we engage in a systematic exploration of the link between ethnic identity and preferences for public policies through a series of individual and aggregated analyses of Afrobarometer survey data from 18 sub-Saharan African countries. We find that in most countries, preferences do vary based on ethnic group membership. This variation is not merely an expression of individual-level socioeconomic differences or of group-level cultural differences. Instead, we suggest that citizens use ethnicity as a group heuristic for evaluating public policies in a few predictable ways: We find more persistent disagreement about public policies between politically relevant ethnic groups and where group disparities in wealth are high.
Campaign Spending in Proportional Electoral Systems
Authors: Johnson Joel W.
Published: October 2012

This article (a) argues that campaign spending is no more effective for challengers than incumbents in congressional elections using candidate-centered forms of proportional representation (PR), (b) develops a new method to estimate spending effects in poly-candidate elections, and (c) demonstrates that spending benefits incumbents as much as challengers in the congressional elections of three separate countries (Brazil, Ireland, and Finland). This article also offers a theory of campaign spending effectiveness that emphasizes a candidate’s relative potential to attract new electoral support as determined by both precampaign familiarity and personal, partisan, and ideological attributes. Challengers and incumbents obtain similar returns to spending under PR because its permissiveness encourages challengers who are limited in their abilities to build electoral support, even when they spend heavily. The theory and findings have important implications for understanding the effects of campaign finance and campaign finance regulations.
Unions Against Governments
Authors: Hamann Kerstin , Johnston Alison , Kelly John
Published: October 2012

Across Western Europe, unions have increasingly engaged in staging general strikes against governments since 1980. This increase in general strikes is puzzling as it has occurred at the same time as economic strikes have been on the decline. We posit that theories developed to explain economic strikes hold little explanatory power in accounting for variation in general strikes across countries and over time. Instead, we develop a framework based on political variables; in particular, whether governments have included or excluded unions in framing policy reforms; the party position of the government; and the type of government. Our empirical analysis, based on a conditional fixed-effects logit estimation of 84 general strikes between 1980 and 2006, shows that union exclusion from the process of reforming policies, government strength, and the party position of the government can provide an initial explanation for the occurrence of general strikes.
Individual Identity Attachments and International Conflict
Authors: Gibler Douglas M. , Hutchison Marc L. , Miller Steven V.
Published: October 2012

This article provides some of the first individual-level evidence for the domestic salience of territorial issues. Using survey data from more than 80,000 individual respondents in 43 separate countries, we examine how conflict affects the content of individual self-identification. We find that international conflict exerts a strong influence on the likelihood and content of individual self-identification, but this effect varies with the type of conflict. Confirming nationalist theories of territorial salience, territorial conflict leads the majority of individuals in targeted countries to identify themselves as citizens of their country. However, individuals in countries that are initiating territorial disputes are more likely to self-identify as members of a particular ethnicity, which provides support for theories connecting domestic salience to ethnic politics. That conflict has variegated effects on identity formation suggests the relationship is not endogenous. Our within-case analysis of changes in Nigerian self-identifications further demonstrates that individuals are quite susceptible to the types and locations of international conflict.
Self-esteem, oral health behaviours, and clinical oral health status in Chinese adults: An exploratorystudy
Authors: Chin Luzy Siu-Hei , Chan Joanne Chung-Yan
Published: October 2012

Objectives:

This is an exploratory study to examine the relations among self-esteem, oral health behaviours and clinical oral health status in Chinese adults. In addition, gender differences in clinical oral health status and oral health behaviours were explored.

Methods:

Participants were 192 patients from a private dental clinic in Hong Kong aged between 18 and 67 years. Prior to oral health examination, participants completed a questionnaire about their oral health behaviours and the Rosenberg’s Self-Esteem Scale. A dentist and a registered dental hygienist examined their tooth condition and clinical oral health status.

Results:

Participants with high self-esteem had better clinical oral health status than participants with low self-esteem despite no difference in their oral health behaviours. Male participants flossed less frequently than female participants but there was no difference in their clinical oral health status. Linear regression analyses showed that only self-esteem was, but gender, age, and tooth conditions were not, a significant predictor of clinical oral health status.

Conclusions:

In general, Chinese adults in Hong Kong had satisfactory oral health behaviours. Chinese adults with high self-esteem had better clinical oral health status than those with low self-esteem. However, oral health behaviours did not differ by level of self-esteem. Implications for implementing psychosocial elements in oral health education were discussed.