bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional spectral domain optical coherence tomography in X linked foveal retinoschisis
Authors: Saxena Sandeep , Manisha  , Meyer Carsten H
Published: April 2013

Spectral domain optical coherence tomography (SD-OCT) was performed in two cases of bilateral X linked foveal retinoschisis of different age groups. On fundus examination spoke wheel and honeycomb pattern of cysts were observed along with retinal nerve fibre layer (RNFL) defects. On SD-OCT, schisis was observed in the outer plexiform layer. External limiting membrane disruption was observed in the subfoveal area, along with disruption of outer nuclear layer (ONL) and inner–outer segment junction. Elevation of ONL due to tractional pull of central palisade was a novel observation. Retinoschisis extended beyond the optic disc up to the nasal region. Extracted RNFL tomogram presented an unprecedented visualisation of schisis along 360° of the optic disc. Tractional elevation in the foveal area and schisis involving nasal region, not observed upon clinical examination, was highlighted on SD-OCT. This investigative modality is an important adjunct in the assessment of foveal retinoschisis.
Charcot foot associated with chronic alcohol abuse
Authors: Arapostathi Christina , Tentolouris Nicholas , Jude Edward B
Published: April 2013

Two patients without a history of diabetes mellitus but with a history of chronic alcohol abuse were referred to our foot clinic due to pain and deformity of the midfoot. On examination both of the feet of the first patient and the left foot of the second patient were swollen and warm but all the inflammatory markers were negative. Subsequent imaging revealed Charcot deformity and the patients were treated with casting and special shoes. The temperature and the swelling of the feet after the offloading improved. x-Rays which were performed 1 and 2 years after the diagnosis did not show any progression of the Charcot deformity.
Isolated laryngeal amyloidosis in a patient with a hoarse voice
Authors: Park Jae Hong , Cheng Hui Mei
Published: April 2013

We present a case of a 59-year-old woman with a hoarse voice of 3 weeks duration. A polypoid lesion involving the anterior aspect of the left vocal cord was detected by flexible fibreoptic endoscopic examination. Flexible bronchoscopic examination was unremarkable. Microlaryngoscopy and excisional biopsy of the laryngeal lesion were carried out. Histology of the biopsy showed stroma exhibiting birefringence under polarised light and a diagnosis of laryngotracheal amyloidosis was made. Systemic amyloidosis was ruled out by further investigations including positron emission tomography scan. Her hoarse voice improved following the excisional biopsy and regular follow-up was arranged for early diagnosis of recurrence.
Unilateral cacosmia: a presentation of maxillary fungal infestation
Authors: Erskine Sally E , Schelenz Silke , Philpott Carl M
Published: April 2013

We present a case of long-standing unilateral cacosmia in a healthy 67-year-old man due to maxillary fungal infestation. Treatment with septoplasty had been attempted 10 years prior but no further investigation or management undertaken and symptoms continued. Subsequent MRI scan revealed significant opacification of the left maxillary sinus. This was readily amenable to treatment by balloon sinuplasty. This yielded viscous grey mucus which grewScedosporium apiospermum. The case highlights the need for careful investigation of olfactory symptoms, including blood tests to exclude systemic causes, endoscopy and imaging where indicated.
Symptomatic bilateral testicular metastasis from carcinoma of the prostate
Authors: Upchurch Emma Ann , Khan Faisal , Okeke Aloysius
Published: April 2013

A man in his late 70s, on hormonal treatment for prostatic adenocarcinoma, presented with bilateral enlarged and painful testes. Bilateral orchidectomy was undertaken and subsequent histological examination revealed both testes completely infiltrated with metastatic prostatic carcinoma.
Peripheral neuropathy induced by red yeast rice in a patient with a known small bowel gastrointestinal tumour
Authors: Kumari Sonia , Sherriff Jennifer M , Spooner David , Beckett Robert
Published: April 2013

Peripheral neuropathy is a well-recognised side effect of the cholesterol-lowering statins. Red yeast rice (RYR) is a traditional Chinese herb, widely available over-the-counter that has also been found to reduce cholesterol. Little data is available regarding its side effect profile. We report a case of a 60-year-old male receiving therapeutic imatinib for metastatic gastrointestinal tumour (GIST), who developed peripheral neuropathy while also taking RYR. The symptoms completely settled following withdrawal of the RYR and he has subsequently continued to take imatinib for over 2 years with no adverse effects. Further research into the safety profile of RYR is needed. The importance of questioning patients about over the counter medications and herbal remedies cannot be overemphasised.
ECG and morphologic adaptations in Arabic athletes: are the European Society of Cardiology's recommendations for the interpretation of the 12-lead ECG appropriate for this ethnicity?
Authors: Riding Nathan R , Salah Othman , Sharma Sanjay , Carré François , George Keith P , Farooq Abdulaziz , Hamilton Bruce , Chalabi Hakim , Whyte Gregory P , Wilson Mathew G
Published: April 2013

Aims

To examine the cardiac structure and function of Arabic athletes and to establish if the European Society of Cardiology (ESC) guidelines for the interpretation of an athlete's ECG are applicable to this ethnicity.

Methods

600 high-level Arabic, 415 Black African, 160 Caucasian male athletes (exercising ≥6 h/week) and 201 Arabic controls presented for ECG and echocardiographic screening.

Results

9 athletes (0.7%) were identified with a cardiac pathology associated with sudden cardiac death. Two Arabics (0.3%) and five Black Africans (1.2%) were diagnosed with hypertrophic cardiomyopathy; a prevalence four times greater in Black African compared to Arabic athletes. Arabic athletes had significantly greater (p<0.05) left ventricular (LV) end-diastolic diameters, maximal LV wall thicknesses and LV mass compared with controls; yet were significantly smaller than Black African and Caucasian athletes. The percentage of athletes demonstrating LV hypertrophy (≥12 mm) was comparable between Arabic, Black African and Caucasian populations (0.5%, 0.5% and 0.6%, respectively). There was no difference in the frequency of an uncommon and training-unrelated ECG between Arabic and Caucasian. However, Black Africans demonstrated a significantly greater prevalence than Arabic and Caucasian athletes (20% vs 8.4% and 6.9%, p<0.001); specifically more right/left atrial enlargement and T wave inversion.

Conclusions

Arabic athletes present significantly smaller cardiac dimensions than Black African and Caucasian athletes. There was no significant difference between the frequency of an uncommon and training-unrelated ECG between Arabic and Caucasian athletes. Therefore, the use of ESC guidelines for the interpretation of an athlete's ECG is clinically relevant and acceptable for use within Arabic athletes.
Cost-effectiveness and quality of life in surgeon versus general practitioner-organised colon cancer surveillance: a randomised controlled trial
Authors: Augestad Knut Magne , Norum Jan , Dehof Stefan , Aspevik Ranveig , Ringberg Unni , Nestvold Torunn , Vonen Barthold , Skrøvseth Stein Olav , Lindsetmo Rolv-Ole
Published: April 2013

Objective

To assess whether colon cancer follow-up can be organised by general practitioners (GPs) without a decline in the patient's quality of life (QoL) and increase in cost or time to cancer diagnoses, compared to hospital follow-up.

Design

Randomised controlled trial.

Setting

Northern Norway Health Authority Trust, 4 trusts, 11 hospitals and 88 local communities.

Participants

Patients surgically treated for colon cancer, hospital surgeons and community GPs.

Intervention

24-month follow-up according to national guidelines at the community GP office. To ensure a high follow-up guideline adherence, a decision support tool for patients and GPs were used.

Main outcome measures

Primary outcomes were QoL, measured by the global health scales of the European Organisation for Research and Treatment of Cancer QoL Questionnaire (EORTC QLQ C-30) and EuroQol-5D (EQ-5D). Secondary outcomes were cost-effectiveness and time to cancer diagnoses.

Results

110 patients were randomised to intervention (n=55) or control (n=55), and followed by 78 GPs (942 follow-up months) and 70 surgeons (942 follow-up months), respectively. Compared to baseline, there was a significant improvement in postoperative QoL (p=0.003), but no differences between groups were revealed (mean difference at 1, 3, 6, 9, 12, 15, 18, 21 and 24-month follow-up appointments): Global Health; Δ−2.23, p=0.20; EQ-5D index; Δ−0.10, p=0.48, EQ-5D VAS; Δ−1.1, p=0.44. There were no differences in time to recurrent cancer diagnosis (GP 35 days vs surgeon 45 days, p=0.46); 14 recurrences were detected (GP 6 vs surgeon 8) and 7 metastases surgeries performed (GP 3 vs surgeon 4). The follow-up programme initiated 1186 healthcare contacts (GP 678 vs surgeon 508), 1105 diagnostic tests (GP 592 vs surgeon 513) and 778 hospital travels (GP 250 vs surgeon 528). GP organised follow-up was associated with societal cost savings (£8233 vs £9889, p<0.001).

Conclusions

GP-organised follow-up was associated with no decline in QoL, no increase in time to recurrent cancer diagnosis and cost savings.

Trial registration

ClinicalTrials.gov identifierNCT00572143.
Contractile protein phosphorylation predicts human heart disease phenotypes
Authors: Walker Lori A. , Fullerton David A. , Buttrick Peter M.
Published: April 2013

Human heart failure has been associated with a low level of thin-filament protein phosphorylation and an increase in calcium sensitivity of contraction relative to both “control” human heart tissue and tissue from small animal models. However, diverse strategies of human tissue procurement and the reliance on tissue obtained from subjects with end-stage heart failure suggest this may be an incomplete characterization. Therefore, we evaluated cardiac left ventricular (LV) biopsy samples from patients with aortic stenosis undergoing valve replacement who presented either with LV hypertrophy and preserved systolic function (Hyp) or with LV dilation and reduced ejection fraction (Dil). In Hyp, total troponin I (TnI) phosphorylation was markedly increased and myosin light chain 2 (MLC2) phosphorylation was unchanged relative to a control group of patients with normal LV function. Conversely, in Dil, total TnI phosphorylation was significantly reduced compared with control subjects and MLC2 phosphorylation was increased. Site-specific analysis of TnI phosphorylation revealed phenotype-specific differences such that Hyp samples demonstrated significant increases in phosphorylation at serine 22/23 and Dil samples had significant decreases at serine 43. The ratio of phosphorylation at the two sites was biased toward serine 22/23 in Hyp and toward serine 43/45 in Dil. Western blot analysis showed that protein phosphatase-1 was reduced in Hyp and protein phosphatase-2 was reduced in Dil. These data suggest that posttranslational modifications of sarcomeric proteins, both singly and in combination, are stage specific. Defining these changes in progressive heart disease may provide important diagnostic and treatment information.
Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system
Authors: Rittirsch Daniel , Flierl Michael A. , Nadeau Brian A. , Day Danielle E. , Huber-Lang Markus S. , Grailer Jamison J. , Zetoune Firas S. , Andjelkovic Anuska V. , Fasano Alessio , Ward Peter A.
Published: April 2013

Zonulin is a protein involved in the regulation of tight junctions (TJ) in epithelial or endothelial cells. Zonulin is known to affect TJ in gut epithelial cells, but little is known about its influences in other organs. Prehaptoglobin2 has been identified as zonulin and is related to serine proteases (MASPs, C1qrs) that activate the complement system. The current study focused on the role of zonulin in development of acute lung injury (ALI) in C57BL/6 male mice following intrapulmonary deposition of IgG immune complexes. A zonulin antagonist (AT-1001) and a related peptide with permeability agonist activities (AT-1002) were employed and given intratracheally or intravenously. Also, zonulin was blocked in lung with a neutralizing antibody. In a dose-dependent manner, AT-1001 or zonulin neutralizing antibody attenuated the intensity of ALI (as quantitated by albumin leak, neutrophil accumulation, and proinflammatory cytokines). A similar pattern was found using the bacterial lipopolysaccharide model of ALI. Using confocal microscopy on sections of injured lungs, staining patterns for TJ proteins were discontinuous, reduced, and fragmented. As expected, the leak of blood products into the alveolar space confirmed the passage of 3 and 20 kDa dextran, and albumin. In contrast to AT-1001, application of the zonulin agonist AT-1002 intensified ALI. Zonulin both in vitro and in vivo induced generation of complement C3a and C5a. Collectively, these data suggest that zonulin facilitates development of ALI both by enhancing albumin leak and complement activation as well as increased buildup of neutrophils and cytokines during development of ALI.
Simultaneous inactivation of GSK-3β suppresses quercetin-induced apoptosis by inhibiting the JNK pathway
Authors: Lee Kyoung-Hee , Yoo Chul-Gyu
Published: April 2013

Quercetin, a ubiquitous bioactive plant flavonoid, has shown to exert a broad range of activities, such as apoptotic, antioxidant, and anti-inflammatory effects. Thus, flavonoids can mediate both cell protection and cell injury. Recently, quercetin has been reported to prevent the progression of emphysema in animal models through antioxidant and anti-inflammatory actions. These findings suggest that quercetin could be a potential treatment option for chronic obstructive pulmonary disease. Its clinical application, however, could be limited by the cytotoxicity of quercetin, and understanding of the apoptotic mechanisms of quercetin is a prerequisite to develop a therapeutic strategy with minimal cytotoxicity. We evaluated the apoptotic effect of quercetin and its molecular mechanisms in normal bronchial epithelial cells (BEAS-2B cells). Quercetin decreased the viability of BEAS-2B cells via apoptosis in a dose- and time-dependent manner. Quercetin activated JNK and increased the expression levels of c-Jun and p53-dependent Bax. Blockade of JNK activation by overexpression of dominant negative JNK1 suppressed apoptosis by quercetin via inhibition of caspase-3 activation and reduction of p53 and Bax expression. Simultaneously, quercetin inactivated glycogen synthase kinase (GSK)-3β, which is phosphatidylinositol 3-kinase/Akt dependent. Overexpression of a constitutively active GSK-3β mutant enhanced quercetin-induced JNK activation. In contrast, overexpression of enzymatically inert GSK-3β inhibited JNK activation, resulting in a suppression of apoptosis by quercetin. Taken together, the JNK-p53 pathway is involved in quercetin-induced apoptosis, and simultaneous inactivation of GSK-3β can attenuate apoptosis in normal bronchial epithelial cells.
Attenuation of inflammatory mediator production by the NF-κB member RelB is mediated by microRNA-146a in lung fibroblasts
Authors: McMillan David H. , Woeller Collynn F. , Thatcher Thomas H. , Spinelli Sherry L. , Maggirwar Sanjay B. , Sime Patricia J. , Phipps Richard P.
Published: April 2013

Lung inflammation can result from exposure to multiple types of inflammatory stimuli. Fibroblasts, key structural cells in the lung that are integral to inflammation and wound healing, produce inflammatory mediators after exposure to stimuli such as IL-1β. We and others have shown that the NF-κB member RelB has anti-inflammatory properties in mice. Little is known, however, about the anti-inflammatory role of RelB in human cells and how it functions. MicroRNAs (miRNAs), a novel class of small, noncoding RNAs, can mediate inflammatory signaling pathways, including NF-κB, through regulation of target gene expression. Our goal was to analyze the anti-inflammatory properties of RelB in human lung fibroblasts. We hypothesized that RelB regulates inflammatory mediator production in lung fibroblasts in part through a mechanism involving miRNAs. To accomplish this, we transfected human lung fibroblasts with a plasmid encoding RelB and small interfering (si)RNA targeting RelB mRNA to overexpress and downregulate RelB, respectively. IL-1β, a powerful proinflammatory stimulus, was used to induce NF-κB-driven inflammatory responses. RelB overexpression reduced IL-1β-induced cyclooxygenase (Cox)-2, PGE2, and cytokine production, and RelB downregulation increased Cox-2 expression and PGE2production. Furthermore, RelB overexpression increased IL-1β-induced expression of miRNA-146a, an NF-κB-dependent miRNA with anti-inflammatory properties, whereas RelB downregulation reduced miRNA-146a. miR-146a overexpression ablated the effects of RelB downregulation on IL-1β-induced Cox-2, PGE2, and IL-6 production, suggesting that RelB mediates IL-1β-induced inflammatory mediator production in lung fibroblasts through miRNA-146a. RelB and miRNA-146a may therefore be new therapeutic targets in the treatment of lung inflammation caused by various agents and conditions.
Cervical Intraepithelial Neoplasia Grade 3 and Adenocarcinoma In Situ: Comparison of ICD-9 Codes and Pathology Results—Kaiser Permanente, United States, 2000–2005
Authors: Surie Diya , Dunne Eileen F. , Naleway Allison L. , Weinmann Sheila , Klein Nicola P. , Baxter Roger , Hutchins Kathleen , Gee Julianne , Markowitz Lauri
Published: April 2013

Background: Cervical intraepithelial neoplasia grade 3+ (CIN3+) and adenocarcinoma in situ incidence will be an important measure of HPV vaccine impact. Integrated healthcare delivery systems, such as Kaiser Permanente, could be used to monitor CIN3+ trends; however, limited evaluations of data from healthcare delivery systems for CIN3+ surveillance exist.

Methods: We compared CIN3+ diagnoses by ICD-9 code with CIN3+ diagnoses by pathology results among 121,211 females aged 11 to 30 years who were continuously enrolled from 2000 to 2005 in either Kaiser Permanente Northern California or Kaiser Permanente Northwest. We calculated sensitivity and positive predictive value of diagnosis by ICD-9 codes using pathology CIN3+ diagnosis as the gold standard.

Results: There were 1,090 women with at least one CIN3+ diagnosis by ICD-9 code 233.1 and 1,200 women with at least one CIN3+ diagnosis by pathology results. The sensitivity of the ICD-9 code for detecting a woman with at least one pathology diagnosis for CIN3+ was 62% (740/1,200); positive predictive value was 68% (740/1,090). Among women with at least one CIN3+ diagnosis by ICD-9 code, 679 (62%) had more than one visit with this code; whereas, among women with at least one CIN3+ diagnosis by pathology, 466 (39%) had more than one CIN3+ pathology result.

Conclusions: ICD-9 codes may underestimate the number of women with at least one CIN3+ diagnosis.

Impact: Pathology results, when available, may provide better estimates of CIN3+ incidence. Cancer Epidemiol Biomarkers Prev; 22(6); 1129–32. ©2013 AACR.
Vitamin D and the Epidemiology of Upper Gastrointestinal Cancers: A Critical Analysis of the Current Evidence
Authors: Trowbridge Ryan , Mittal Sumeet K. , Agrawal Devendra K.
Published: April 2013

Prospective analyses have yet to uncover a consistent relationship between vitamin D status and incidence and mortality of rarer cancers including esophageal and upper gastrointestinal cancers. We searched PubMed for literature about the epidemiology of upper gastrointestinal cancers and vitamin D published over the last decade and then summarized and critiqued the results of these studies in this review. The search yielded nine relevant studies. Overall, no consistent relationship was reported between serum vitamin D levels or a surrogate and upper gastrointestinal cancers. Four studies reported negative correlations between vitamin D status and upper gastrointestinal cancer, three reported positive correlations, one reported no correlation, and one reported both positive and negative correlations. No relationship has been established on the basis of epidemiologic data, but studies examining sun exposure consistently report an inverse association with esophageal cancer. The current literature is limited by the methods used to assess vitamin D status, lack of specific data for the types of upper gastrointestinal cancer, and failure to establish a temporal relationship between vitamin D status assessment and presentation of upper gastrointestinal cancer. It is possible that the lack of a consistent relationship is a consequence of inaccurate and imprecise assessment of vitamin D status. Cancer Epidemiol Biomarkers Prev; 22(6); 1007–14. ©2013 AACR.
Let-7c Governs the Acquisition of Chemo- or Radioresistance and Epithelial-to-Mesenchymal Transition Phenotypes in Docetaxel-Resistant Lung Adenocarcinoma
Authors: Cui Shi-Yun , Huang Jia-Yuan , Chen Yi-Tian , Song Hai-Zhu , Feng Bing , Huang Gui-Chun , Wang Rui , Chen Long-Bang , De Wei
Published: April 2013

MicroRNA (miRNA) expression and functions have been reported to contribute to phenotypic features of tumor cells. Although targets and functional roles for many miRNAs have been described in lung adenocarcinoma (LAD), their pathophysiologic roles in phenotypes of chemoresistant LAD cells are still largely unclear. Previously, docetaxel (DTX)-resistant LAD cell lines (SPC-A1/DTX and H1299/DTX) were established by our laboratory and displayed chemo- or radioresistance and mesenchymal features with enhanced invasiveness and motility. Unbiased miRNA profiling indicated that let-7c (MIRLET7C) was significantly downregulated in SPC-A1/DTX cells. Ectopic let-7c expression increased the in vitro and in vivo chemo- or radiosensitivity of DTX-resistant LAD cells through enhanced apoptosis, reversal of epithelial-to-mesenchymal phenotypes, and inhibition of in vivo metastatic potential via inactivation of Akt phosphorylation, whereas a let-7c inhibitor decreased the chemo- or radiosensitivity of parental cells. Further investigation suggested that let-7c significantly reduced the luciferase activity of a Bcl-xL 3′-UTR-based reporter, concordant with reduced Bcl-xL protein levels. Additionally, siRNA-mediated Bcl-xL knockdown mimicked the same effects of let-7c precursor, and enforced Bcl-xL expression partially rescued the effects of let-7c precursor in DTX-resistant LAD cells. Furthermore, we found that Bcl-xL was significantly upregulated in DTX-nonresponding LAD tissues, and its expression was inversely correlated with let-7c expression. This study suggests an important role for let-7c in the molecular etiology of chemoresistant lung adenocarcinoma. Mol Cancer Res; 11(7); 699–713. ©2013 AACR.
Chronic Therapy With a Partial Adenosine A1-Receptor Agonist Improves Left Ventricular Function and Remodeling in Dogs With Advanced Heart Failure
Authors: Sabbah Hani N. , Gupta Ramesh C. , Kohli Smita , Wang Mengjun , Rastogi Sharad , Zhang Kefei , Zimmermann Katja , Diedrichs Nicole , Albrecht-Küpper Barbara E.
Published: April 2013

Background—

Adenosine elicits cardioprotection through A1-receptor activation. Therapy with adenosine A1-receptor agonists, however, is limited by undesirable actions of full agonism, such as bradycardia. This study examined the effects of capadenoson (CAP), a partial adenosine A1-receptor agonist, on left ventricular (LV) function and remodeling in dogs with heart failure.

Methods and Results—

Twelve dogs with microembolization-induced heart failure were randomized to 12 weeks oral therapy with CAP (7.5 mg BID; n=6) or to no therapy (control; n=6). LV end-diastolic and end-systolic volumes, ejection fraction, plasma norepinephrine, and n-terminal pro–brain natriuretic peptide were measured before (pre) and 1 and 12 weeks after therapy (post). LV tissue obtained at post was used to assess volume fraction of interstitial fibrosis, sarcoplasmic reticulum calcium ATPase-2a activity, expression of mitochondria uncoupling proteins (UCP) and glucose transporters (GLUT). In controls, end-diastolic and end-systolic volumes increased and ejection fraction decreased significantly from pre to post (ejection fraction, 30±2 versus 27±1%;
P
<0.05). In CAP-treated dogs, end-diastolic volume was unchanged; ejection fraction increased significantly after 1 week (36±2 versus 27±2%;
P
<0.05) with a further increase at post (39±2%;
P
<0.05), whereas end-systolic volume decreased. CAP significantly decreased volume fraction of interstitial fibrosis, normalized sarcoplasmic reticulum calcium ATPase-2a activity and expression of UCP-2 and UCP-3, and GLUT-1 and GLUT-2 and significantly decreased plasma norepinephrine and n-terminal pro–brain natriuretic peptide.

Conclusions—

In heart failure dogs, CAP improves LV function and prevents progressive remodeling. Improvement of LV systolic function occurs early after initiating therapy. The results support development of partial adenosine A1-receptor agonists for the treatment of chronic heart failure.
Cezanne Regulates Inflammatory Responses to Hypoxia in Endothelial Cells by Targeting TRAF6 for Deubiquitination
Authors: Luong Le A. , Fragiadaki Maria , Smith Jennifer , Boyle Joseph , Lutz Jens , Dean Jonathan L.E. , Harten Sarah , Ashcroft Margaret , Walmsley Sarah R. , Haskard Dorian O. , Maxwell Patrick H. , Walczak Henning , Pusey Charles , Evans Paul C.
Published: April 2013

Rationale:

Hypoxia followed by reoxygenation promotes inflammation by activating nuclear factor κB transcription factors in endothelial cells (ECs). This process involves modification of the signaling intermediary tumor necrosis factor receptor–associated factor 6 with polyubiquitin chains. Thus, cellular mechanisms that suppress tumor necrosis factor receptor–associated factor 6 ubiquitination are potential therapeutic targets to reduce inflammation in hypoxic tissues.

Objective:

In this study, we tested the hypothesis that endothelial activation in response to hypoxia-reoxygenation can be influenced by Cezanne, a deubiquitinating enzyme that cleaves ubiquitin from specific modified proteins.

Methods and Results:

Studies of cultured ECs demonstrated that hypoxia (1% oxygen) induced Cezanne via p38 mitogen–activated protein kinase–dependent transcriptional and post-transcriptional mechanisms. Hypoxia-reoxygenation had minimal effects on proinflammatory signaling in unmanipulated ECs but significantly enhanced Lys63 polyubiquitination of tumor necrosis factor receptor–associated factor 6, activation of nuclear factor κB, and expression of inflammatory genes after silencing of Cezanne. Thus, although hypoxia primed cells for inflammatory activation, it simultaneously induced Cezanne, which impeded signaling to nuclear factor κB by suppressing tumor necrosis factor receptor–associated factor 6 ubiquitination. Similarly, ischemia induced Cezanne in the murine kidney in vascular ECs, glomerular ECs, podocytes, and epithelial cells, and genetic deletion of Cezanne enhanced renal inflammation and injury in murine kidneys exposed to ischemia followed by reperfusion.

Conclusions:

We conclude that inflammatory responses to ischemia are controlled by a balance between ubiquitination and deubiquitination, and that Cezanne is a key regulator of this process. Our observations have important implications for therapeutic targeting of inflammation and injury during ischemia-reperfusion.
Spacetime as a Multicursal Labyrinth in Literature with Application to Philip K. Dick’s The Man in the High Castle
Authors: Everett Justin , Halpern Paul
Published: April 2013

Abstract

We examine the narrative structure of The Man in the High Castle by Philip K. Dick. We place the novel in the context of the alternate history genre of speculative fiction. Noting its complex plot with multiple timelines, we apply the theoretical ideas of Mikhail Bakhtin and Umberto Eco and show how its chronotope, or relationship between space and time, resembles that of a multicursal labyrinth. We connect this analysis with ideas in quantum physics, particularly the Many Worlds Interpretation, and show how it explains the ambiguity of the novel’s ending, and the failure of the characters to reach their goals. In particular, the characters’ search for truth is thwarted by the existence of multiple truths in a maze of competing realities.
Emergences in Quantum Measurement Processes
Authors: Balian Roger
Published: April 2013

Abstract

Quantum mechanics is acknowledged as the fundamental theory on which the whole fabric of physics is supposed to rely. And yet, the features of quantum measurements, processes that provide information about microscopic objects, seem to contradict the principles of quantum mechanics. We make a qualitative presentation of this long standing problem and give an idea of recent progress in the elucidation of the paradox. Although governed solely by the quantum equations of motion, the dynamical process involving the tested system and the measuring apparatus veils the quantum oddities that oppose our standard logic and gives rise to the expected properties of measurements. In spite of the irreducibly probabilistic nature of the underlying quantum physics, classical concepts emerge, such as standard probabilities, ordinary correlations, disappearance of quantum fluctuations, and the possibility of making statements about individual systems.
The Emergence of Time: Kant, Bergson, and Modern Physics
Authors: Bouton Christophe
Published: April 2013

Abstract

This paper deals with the problem of the emergence of time in three different ways, at the intersection of the history of philosophy and the history of science: 1) the emergence of time with subjectivity examined on the basis of Kant’s idealism; 2) the emergence of time with life, considered in the light of the work of Bergson; 3) the emergence of time with the Universe, in relation to the notions of ‘The Big Bang’ and ‘The Planck Wall’. It concludes that the idea of the emergence of time is inconsistent in a diachronic sense, and problematic in a synchronic sense. One meaning could, however, be accorded to this notion: with life, a new relation to time has emerged and has attained one of its most developed forms with the human being.
The Emergence of Theatrical Praxis as a Mediative Technology for Individual Consciousness
Authors: Magnus Erica W.
Published: April 2013

Abstract

Most theatre histories attest the seemingly sudden appearance in ancient Greece of a theatrical form in full bloom. If, as critic Joseph Frank suggests, major changes in aesthetic forms “always involve major changes in the sensibility of a particular cultural period,” the emergence of a new aesthetic form leads us to examine the historical record for transitions of some magnitude. The 5th century BCE was a period of radical change, particularly with regard to ideas about time.

I propose that western theatre emerged in answer to psychic needs engendered by the new experience of time in the 5th century BCE. Through performance and the thematic concerns of the plays, the time and space of individual life was measured in relation to the demands of collective and cosmic concerns. I contend that theatrical praxis is, in Foucault’s phrase, a “technology of the self ” through which human beings learn the parameters of identity and personal agency.1
Thresholds of Emergence
Authors: Turner Frederick
Published: April 2013

Abstract

Pascal’s wager implies the incommensurability of quality and quantity, but the emergence of new order with qualitatively unprecedented states upon the quantitative crossing of natural thresholds questions any simple dualism and points to special characteristics of time. The presence of natural thresholds requires that the universe cannot be understood in a purely analog fashion, as composed of smooth gradients analysable by probabilistic and statistical means. It must also be seen as constitutively granular and quantized, like the counters and turns of a game, and capable of unpredictable creativity. Mathematics implies a threshold between the computable and the uncomputable. Physics requires quanta and a distinction between the reversible and the irreversible. Chemistry dictates catastrophic changes of state. Evolutionary biology requires distinct competing individuals. Neuroscience requires the emergence of qualitatively irreducible cognitive capacities. Economic activity implies unpredictable financial crises. Information theory requires distinct signals distinguishable from noise. Freedom and responsibility, art and poetry can be understood in the light of threshold-crossing. American pragmatism, French evolutionary philosophy, chaos and complexity theory, game theory and the framework provided by J.T. Fraser’s work can guide future investigations of natural thresholds.
Locations of Mythical Exile: Two Mythical Models Accounting for the Phenomenon of the Diurnal Solar Movement
Authors: Bilić Tomislav
Published: April 2013

Abstract

Various mythical ‘exiles’, gods (Cronus), heroes (Cadmus), and other individuals (Ophion, Typhon, Ogygus, Briareus) or groups (Cyclopes) were conceived as exiled for various reasons, but mainly because of a struggle with Zeus. Locations of their mythical exile were regularly conceived as distant, extreme, inaccessible, and, sometimes, out of this world. Consequently, the terms sometimes associated with those mythical exiles are ἔσχατα, ἄκρος, and πέρατα. Most of the exiles were at some point placed in Tartarus, a term more or less applicable to a section of Hades; but they were regularly conceived as continuing their existence by the shore of the mythical Oceanus, most probably in the farthest West. In a number of cases, both versions of the story existed, and they probably referred to the same thing: one can be at the ἔσχατα, ἄκρος, or πέρατα both under earth and at its western extremity. This fact is explained by the existence of two mythical models accounting for the diurnal solar movement.
Binarism in the Disticha Catonis
Authors: Connolly Serena
Published: April 2013

Abstract

Thematic and structural binarism pervades the Disticha Catonis. It appeals to a fundamental mode of cognition rooted in an early and critical stage of human cognitive development that uses pairs to structure and organize our thinking and perceptions. Partly as a result of its binarism, the collection’s maxims are easily understood and remembered, which explains why they were read or quoted by adults in the Classical and post-Classical periods and were important in the education of children in the medieval period and later.
The Untold Death of Laertes. Revaluating Odysseus’s Meeting with His Father
Authors: Sels Nadia
Published: April 2013

Abstract

This article discusses the narrative function and symbolism of the Laertes scene in the twenty-fourth book of the Odyssey. By pointing out the scene’s connections to other passages (the story of Penelope’s web, the first and second nekuia, the farewell to the Phaeaceans, the Argus scene, but also the twenty-fourth book of the Iliad) and by tackling some of the textual problems that it poses (the apparent cruelty of Odysseus’s lies to his father, the double layers of meaning in his fictions, the significance of the sêma of the trees), this article aims to point out how the Laertes scene is tightly woven into the larger thematic and symbolical tissue of the Odyssey. Odysseus’s reunion with his father is conclusive to the treatment of some important themes such as death and burial, reciprocal sense of love and duty and the succession of generations. It will be argued that the untold death of Laertes becomes paradigmatic for the fate Odysseus himself chooses, and for the way in which the epic as a whole deals with the problem of mortality.
Comparison of Therapeutic Lipid Target Achievements Among High-Risk Patients in Oman
Authors: Al-Waili Khalid , Al-Zakwani Ibrahim , Al-Dughaishi Tamima , Baneerje Yajnavalka , Al-Sabti Hilal , Al-Hashmi Khamis , Farhan Hatem , Habsi Khadija Al , Al-Hinai Ali T. , Al-Rasadi Khalid
Published: April 2013

We compared therapeutic lipid target achievements among patients with diabetes or coronary heart disease (CHD) in Oman. A retrospective chart review of 94 patients was conducted at an outpatient clinic in Sultan Qaboos University Hospital, Muscat, Oman. The variables included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (apo B). The overall mean age of the cohort was 59 ± 12 years, 54% were male, 66% were diabetic, 48% hypertensive, 45% had CHD, 94% were on simvastatin, 4% were on fenofibrate, and 2% were on both simvastatin and fenofibrate. Lipid goal attainments of calculated LDL-C (<2.6 mmol/L), apo B (<0.9 g/L), and non-HDL-C (<3.36 mmol/L) were reached in 52%, 39%, and 53% of the patients, respectively. A significant proportion of high-risk patients treated with lipid-lowering agents reach LDL-C but not the apo B treatment targets, suggesting that the use of apo B target values should also be considered.
Increased Mean Platelet Volume in Hypertrophic Cardiomyopathy
Authors: Icli Atilla , Aksoy Fatih , Dogan Abdullah , Arslan Akif , Akcay Salaheddin , Yücel Habil , Ersoy Ibrahim , Gorgulu Ozkan
Published: April 2013

Thromboembolic events may be seen in patients with hypertrophic cardiomyopathy (HCM). We investigated the mean platelet volume (MPV), an indicator of platelet activation in patients with HCM. This study included 112 patients with HCM, in which 40 were patients with hypertrophic obstructive cardiomyopathy (HOCM), and 106 were control participants. The MPV was significantly higher in patients with HCM than in controls (9.1 ± 0.3 vs 7.9 ± 0.3 fL, P = .01). In the subgroup analyses, MPV was also higher in patients with HOCM compared to those with hypertrophic nonobstructive cardiomyopathy (HNCM; 9.3 ± 0.3 vs 9.0 ± 0.2 fL, P = .01). Similarly, patients with HNCM had higher MPV values than controls (9.0 ± 0.2 vs 7.9 ± 0.3 fL, P = .01). The MPV was significantly and positively correlated with left ventricular outflow tract (LVOT) obstruction ( r = .42, P = .001) and septal thickness ( r =.62, P = .001). In linear regression analysis, MPV was independently associated only with septal thickness (β = .07, 95% confidence interval: 0.04-0.09, P = .001). The MPV can be elevated in patients with HCM regardless of the obstruction of LVOT and may be associated with the severity of septal thickness.
Symptomatic Atlantoaxial Instability in an Adolescent with Trisomy 21 (Down’s syndrome)
Authors: Dedlow E. Rosellen , Siddiqi Siraj , Fillipps Donald J. , Kelly Maria N. , Nackashi John A. , Tuli Sanjeev Y.
Published: April 2013

Atlantoaxial instability (AAI) occurs in 15% of children with Trisomy 21. Health supervision guidelines were revised by the American Academy of Pediatrics in 2011 to reflect advances in care for children with special health care needs (CSHCN). Previous guidelines recommended cervical spine radiological screenings in preschool years to evaluate for atlantoaxial instability. For patients with negative screening, re-screening was recommended if they wished to compete in the Special Olympics, or became symptomatic. We present the case of an adolescent who developed a symptomatic atlantoaxial dislocation despite previous negative radiological screening at the age three (under the 2001 guidelines). This case report highlights the revisions in the 2011 guidelines for health supervision and anticipatory guidance. It underlines the need for a high index of suspicion if symptoms develop. It also addresses the need for a medical home for CSHCN, with health care providers who know the child’s baseline health status.
Diaspora
Authors: Ben-Rafael Eliezer
Published: April 2013

Contemporary diasporas are studied from many different perspectives. One widely acknowledged aspect is their capacity to illustrate dual homeness, and their challenging national cultures’ aspiration to sociocultural unity. Insertion into new societies tends today to erode the singularity of diasporic communities, but the symbols they retain or create may still warrant cultural reproduction as transnational entities. The conceptual distinction between collective identity, identification, and identifying is helpful when considering how diasporas have become a factor in the multiculturalization of present-day societies, while themselves becoming multicultural entities through the influence of the cultures prevailing in the diverse environments of their dispersed communities. The incoherent – even chaotic – realities these contradictory tendencies generate for analysts are not necessarily perceived in these terms by the actors. Their presence in societies, their impact on non-diasporic populations, the new relations they create between original and new homelands, and above all their endeavor as interconnected cross-national spaces, represent developments that contribute to moving society towards a new era.
Recent progress in understanding marine-terminating Arctic outlet glacier response to climatic and oceanic forcing
Authors: Carr J. Rachel , Stokes Chris R. , Vieli Andreas
Published: April 2013

Until relatively recently, it was assumed that Arctic ice masses would respond to climatic/oceanic forcing over millennia, but observations made during the past two decades have radically altered this viewpoint and have demonstrated that marine-terminating outlet glaciers can undergo dramatic dynamic change at annual timescales. This paper reviews the substantial progress made in our understanding of the links between marine-terminating Arctic outlet glacier behaviour and the ocean-climate system during the past 20 years, when many ice masses have rapidly lost mass. Specifically, we assess three primary climatic/oceanic controls on outlet glacier dynamics, namely air temperature, ocean temperature and sea ice concentrations, and discuss key linkages between them. Despite recent progress, significant uncertainty remains over the response of marine-terminating outlet glaciers to these forcings, most notably: (1) the spatial variation in the relative importance of each factor; (2), the contribution of glacier-specific factors to glacier dynamics; and (3) the limitations in our ability to accurately model marine-terminating outlet glacier behaviour. Our present understanding precludes us from identifying patterns of outlet glacier response to forcing that are applicable across the Arctic and we underscore the potential danger of extrapolating rates of mass loss from a small sample of study glaciers.
A numerical method for elasto-plastic notch-root stress–strain analysis
Authors: Ince Ayhan , Glinka Grzegorz
Published: April 2013

In this article, a computational modeling method of the multiaxial stress–strain notch analysis has been developed to compute elasto-plastic notch-tip stress–strain responses using linear elastic finite element results of notched components. Application and validation of the multiaxial stress–strain notch analysis model were presented by comparing computed results of the model to the experimental data of SAE 1070 steel notched shaft subjected to several nonproportional load paths. Based on the comparison between the experimental and computed strain histories, the elasto-plastic stress–strain model predicted notch strains with reasonable accuracy using linear elastic finite element stress histories. The elasto-plastic stress–strain notch analysis model provides an efficient and simple analysis method preferable to expensive experimental component tests and more complex and time-consuming incremental nonlinear finite element analysis. The elasto-plastic stress–strain model can thus be employed to perform fatigue life and fatigue damage estimates associated with the local material deformation.
An effective means for evaluating mixed-mode I/III stress intensity factors using single-edge notch beam specimen
Authors: Ahmadi-Moghadam Babak , Taheri Farid
Published: April 2013

The main objective of this study is to produce a set of practical equations, by which one could evaluate mixed-mode I/III stress intensity factors by conducting a simple mode I single-edge notch bend specimen test as per ASTM D5054. To establish the proposed equations, a comprehensive finite element analysis is conducted to map the stress intensity factors’ distribution through the thickness of the specimen with the aim of establishing the most effective loading condition for evaluating the mode stress intensity factors. An experimental investigation is also conducted to obtain the ultimate fracture load and establish the fracture mechanism under the mixed-mode loading state. A set of correction factors is also proposed, which accounts for the influence of orientation of the initial crack and the applied load on the stress intensity factors.
Treatment of orthostatic headache without intracranial hypotension: A case report
Authors: Gil-Gouveia Raquel
Published: April 2013

Introduction:

Orthostatic headache is very suggestive of intracranial hypotension. It has a good prognosis as it usually responds to conservative treatment or epidural blood patches.

Case report:

A 36-year-old female presented with severe and prolonged orthostatic headache starting after a seizure. No stigma of intracranial hypotension was detected on brain MRI, and intracranial pressure was within normal range. No imaging evidence of a fistula was found. She was refractory to symptomatic treatment including five epidural blood patches. Progressive improvement occurred simultaneously to the introduction of vitamin A supplementation.

Discussion:

A series of six similar patients is discussed, in which five patients remained severely symptomatic and workdisabled at an average follow-up of four years. It is proposed that the pathophysiological mechanism producing orthostatic headache might not be dependent on intracranial hypotension and could respond to vitamin A.