bluuebunny/crossref_metadata_2025 huggingface dataset:
The Global Circulation of Charles Dickens’s Novels
Authors: Gagnier Regenia
Published: January 2013

Following previous contributions on Dickens within the Global Circulation Project, this essay synthesizes research on the global circulation of Dickens in this year of his Bicentenary 2012. It has two sections, beginning with the state of Dickens in the local environment of the UK and moving to the place of Dickens in current debates about World Literatures and Translation Studies. Its second and main section focuses on Dickens outside Britain, Europe, and North America, in terms of geography as well as literary traditions: New Zealand, Australia, Africa, Socialist Poland, Chinese, Japanese, and Arabic, with some reference to more widely studied areas such as Spanish, Russian, and Indian literary traditions. It urges us to think less in terms of originality and derivation than of circulation, appropriation, use, and their corollaries of transculturation, revoicing, mediation, and triangulation. When we consider the role of Dickens in cultural translation and transculturation, he has “meant” both migration and settlement, class warfare, revolution, critique of neocolonial ideological state apparatuses, care of orphans/children, critique of capitalism, socialism, gender and domestic relations, sociology and psychology of crime and deprivation, Christian solutions to social divisions and suffering, dialect, and the vernaculars of the street. He has represented extreme psychology and individual identity, for which themuletilla(in Galdós, “tagging” for Katherine Mansfield in New Zealand), a pet word or phrase repeated inadvertently showing a character’s “tic” or deep psychology, was much adapted. He has also represented the divisions between country and city, as in Henry Lawson’s studies of an Australian national ethos torn between its traditions of the bush and its rapid centralization in cities. Societies caught between traditional cultures and the forces of modernization give rise to “Dickensian” novels, “Dickensian” characters, “Dickensian” affect, “Dickensian” institutions and so forth, showing that comparable conditions give rise to formal resemblances.
Two Paths for Writing by Women in Modernist Studies
Authors: Evans Elizabeth F.
Published: January 2013

In its turn to transnational and interdisciplinary methods and subjects, the field of modernist studies has moved decisively away from gender‐based analyses of literary texts. Because feminist and gender‐focused scholarship played a crucial role in claiming a place for literature by women in the research and teaching of modernism, this expansionist trend raises concerns about the future of women’s literature in modernist studies. This paper argues that this path changes the questions we ask, but energizes more than sidelines the study of writing by women. Not only have expansionist tendencies in modernist studies historically been good for the inclusion of literature by women, but interdisciplinary methodologies and transnational inquiry has both invigorated work on canonical figures and provided new approaches to understudied writers. I follow a brief review of recent contributions to the study of women’s writing that take part in these developments with a more focused treatment of Dorothy Richardson studies, which have blossomed under transnational and interdisciplinary inquiry.

This paper also explores another development, the significance of which for modernist studies (and the humanities more broadly) has hardly begun to be recognized: the increasing availability of digital texts and development of computational methods. We are poised to take advantage of the new accessibility of lesser‐known works, many of which have fallen out of print, in our research and teaching. Further, new technologies promise to revolutionize the ways we study literature. The digitization of literary corpora and the development of methods to mine the digitized texts for information allow us to ask new questions of literature. It remains only for scholars of modernist writing by women to continue asking new questions.
Activity of the mTOR inhibitor RAD001, the dual mTOR and PI3‐kinase inhibitor BEZ235 and the PI3‐kinase inhibitor BKM120 in hepatocellular carcinoma
Authors: Kirstein Martha M. , Boukouris Aristeidis E. , Pothiraju Deepika , Buitrago‐Molina Laura E. , Marhenke Silke , Schütt Jutta , Orlik Johanna , Kühnel Florian , Hegermann Jan , Manns Michael P. , Vogel Arndt
Published: January 2013

Background

Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide with only few therapeutic options for patients with advanced disease. There is growing evidence indicating that activation of the PI3K/Akt/mTOR pathway plays an important role in HCC and therefore represents a promising target for novel therapeutic approaches. The aim of this study was to evaluate and compare the antitumour activity of the mTOR inhibitor RAD001, the dual mTOR and PI3‐kinase inhibitor BEZ235 and the PI3‐kinase inhibitor BKM120 in vitro and in vivo.

Experimental Design

The antitumour effects of RAD001, BEZ235 and BKM120 were analysed in seven hepatoma cell lines as mono and combination therapy with Doxorubicin, Cisplatin, Irinotecan or 5‐Flourouracil in vitro and in xenografts. Cell‐cycle progression, apoptosis, and autophagy were analysed. Furthermore, effects on mitochondrial respiration and glycolysis were assessed.

Results

Treatment with RAD001, BEZ235 and BKM120 markedly reduced tumour cell viability. Combination of PI3K inhibitors with chemotherapy was most effective. RAD001, BEZ235 and BKM120 reduced tumour growth mainly by inhibiting cell‐cycle progression rather than by inducing apoptosis. Interestingly, the antitumour effects were strongly associated with a reduction of mitochondrial respiration. BKM120, which exhibited the strongest antiproliferative effect, most strongly impaired oxidative phosphorylation compared with the other drugs.

Conclusions

In this study, BKM120 showed the strongest antitumour activity. Our findings suggest impairment of mitochondrial function as a relevant mechanism of BKM120. Moreover, combination of PI3K and mTOR inhibitors with cytotoxic agents could be promising option for non‐cirrhotic HCC patients.
The natural history and long‐term outcomes in patients with chronic hepatitis C genotype 4 after interferon‐based therapy
Authors: Alfaleh Faleh Z. , Alswat Khalid , Helmy Ahmed , Al‐hamoudi Waleed , El‐sharkawy Mohamed , Omar Mohanned , Shalaby Ahmed , Bedewi Mohaned A. , Hadad Qais , Ali Safiyya M. , Alfaleh Ahmad , Abdo Ayman A.
Published: January 2013

Background & Aims

Hepatitis C virus (HCV) genotype 4 (G4) infection is common in the Middle East. Post‐treatment long‐term outcomes have not been reported in these patients. This study evaluates these outcomes in patients after interferon‐based therapy.

Patients and methods

A total of 157 patients were followed from June 2001 to February 2012. Descriptive and analytical statistics, cumulative outcomes and the independent predictors of disease progression were calculated.

Results

The overall age was 48.0 ± 11.8 years, 75 (47.8%) were males and 53 (70.7%) of 75 who were genotyped had G4. The follow‐up period was 63.8 ± 32.8 months. Sustained virological response (SVR) was achieved in 62 (39.5%) and 24 (45.3%) patients in the whole group and the G4 subgroup respectively. Among the whole cohort and the G4 subgroup, disease progressed in 59 (37.6%) and 21 (39.6%), respectively, with less progression in the SVR groups; 15/62 (24.2%) and 3/24 (12.5%) compared with non‐responders; 44 (46.3%) and 18 (62.1%) with P = 0.01 and 0.001 respectively. Multivariate logistic regression analysis showed that having diabetes mellitus (P = 0.03), higher baseline APRI score (P = 0.00) and non‐SVR (P = 0.00) were independent predictors of disease progression. G4 patients showed similar results, but ‘non‐SVR’ (P = 0.00) was the only independent predictor of progression. Eight patients died and four developed HCC all among the non‐SVR group only.

Conclusions

This study describes, for the first time, the natural history and demonstrates the beneficial long‐term effects of interferon‐based therapy in HCV G4 patients.
Alteration assemblages in the Miller Range and Elephant Moraine regions of Antarctica: Comparisons between terrestrial igneous rocks and Martian meteorites
Authors: Hallis L. J.
Published: January 2013

The weathering products present in igneous terrestrial Antarctic samples were analyzed, and compared with those found in the four Miller Range nakhlite Martian meteorites. The aim of these comparisons was to determine which of the alteration phases in the Miller Range nakhlites are produced by terrestrial weathering, and what effect rock composition has on these phases. Antarctic terrestrial samples MIL 05031 and EET 96400, along with the Miller Range nakhlites MIL 03346 and 090032, were found to contain secondary alteration assemblages at their externally exposed surfaces. Despite the difference in primary mineralogy, the assemblages of these rocks consist mostly of sulfates (jarosite in MIL 05031, jarosite and gypsum in EET 96400) and iddingsite‐like Fe‐clay. As neither of the terrestrial samples contains sulfur‐bearing primary minerals, and these minerals are rare in the Miller Range nakhlites, it appears that SO42−, possibly along with some of the Na+, K+, and Ca+ in these phases, was sourced from wind‐blown sea spray and biogenic emissions from the southern ocean. Cl enrichment in the terrestrially derived “iddingsite” of MIL 05031 and MIL 03346, and the presence of halite at the exterior edge of MIL 090032, can also be explained by this process. However, jarosite within and around the olivine‐bound melt inclusions of MIL 090136 is present in the interior of the meteorite and, therefore, is probably the product of preterrestrial weathering on Mars.
Replacement versus Historical Cost Profit Rates: What is the Difference? When Does it Matter?
Authors: Basu Deepankar
Published: January 2013

This paper explains the Bureau of Economic Analysis methodology for computing historical cost and replacement cost measures of the net stock of capital in the US economy. It is demonstrated that there exists a threshold rate of inflation in the price of capital goods that keeps the percentage difference between the two capital stock measures constant. Hence, over periods when average inflation in the price index for capital goods is equal to the threshold value, historical cost and replacement cost profit rates would show equal percentage changes; an example of such a period for the US economy is 1946–2010.
Direct evidence for the adaptive role of copy number variation on antifolate susceptibility in Plasmodium falciparum
Authors: Heinberg Adina , Siu Edwin , Stern Chaya , Lawrence Elizabeth A. , Ferdig Michael T. , Deitsch Kirk W. , Kirkman Laura A.
Published: January 2013

Resistance to antimalarials targeting the folate pathway is widespread. GTP‐cyclohydrolase (gch1), the first enzyme in this pathway, exhibits extensive copy number variation (CN) in parasite isolates from areas with a history of longstanding antifolate use. Increased CN of gch1 is associated with a greater number of point mutations in enzymes targeted by the antifolates, pyrimethamine and sulphadoxine. While these observations suggest that increases in gch1 CN are an adaptation to drug pressure, changes in CN have not been experimentally demonstrated to directly alter drug susceptibility. To determine if changes in gch1 expression alone modify pyrimethamine sensitivity, we manipulated gch1 CN in several parasite lines to test the effect on drug sensitivity. We report that increases in gch1 CN alter pyrimethamine resistance in most parasites lines. However we find evidence of a detrimental effect of very high levels of gch1 overexpression in parasite lines with high endogenous levels of gch1 expression, revealing the importance of maintaining balance in the folate pathway and implicating changes in gch1 expression in preserving proper metabolic flux. This work expands our understanding of parasite adaptation to drug pressure and provides a possible mechanism for how specific mutations become fixed within parasite populations.
Effect of inhaled corticosteroids on the microbiology of the respiratory tract
Authors: Martin Matthew , Shaw Dominick
Published: January 2013

See article, page 272
Early knee changes in dancers identified by ultra‐high‐field 7 T MRI
Authors: Chang G. , Diamond M. , Nevsky G. , Regatte R. R. , Weiss D. S.
Published: January 2013

We aimed to determine whether a unique, ultra‐high‐field 7 T magnetic resonance imaging (MRI) scanner could detect occult cartilage and meniscal injuries in asymptomatic female dancers. This study had Institutional Review Board approval. We recruited eight pre‐professional female dancers and nine non‐athletic, female controls. We scanned the dominant knee on a 7 T MRI scanner using a three‐dimensional fast low‐angle shot sequence and a proton density, fast spin‐echo sequence to evaluate cartilage and menisci, respectively. Two radiologists scored cartilage (International Cartilage Repair Society classification) and meniscal (Stoller classification) lesions. We applied two‐tailed z‐ and t‐tests to determine statistical significance. There were no cartilage lesions in dancers or controls. For the medial meniscus, the dancers demonstrated higher mean MRI score (2.38 ± 0.61 vs 1.0 ± 0.97, P < 0.0001) and higher frequency of mean grade 2 lesions (88% vs 11%, P < 0.01) compared with the controls. For the lateral meniscus, there was no difference in score (0.5 ± 0.81 vs 0.5 ± 0.78, P = 0.78) in dancers compared with the control groups. Asymptomatic dancers demonstrate occult medial meniscal lesions. Because this has been described in early osteoarthritis, close surveillance of dancers' knee symptoms and function with appropriate activity modification may help maintain their long‐term knee health.
Dependence on proton energy of degradation of AlGaN/GaN high electron mobility transistors
Authors: Liu Lu , Lo Chien-Fong , Xi Yuyin , Wang Yuxi , Ren Fan , Pearton Stephen J. , Kim Hong-Yeol , Kim Jihyun , Fitch Robert C. , Walker Dennis E. , Chabak Kelson D. , Gillespie James K. , Tetlak Stephen E. , Via Glen D. , Crespo Antonio , Kravchenko Ivan I.
Published: January 2013

The effects of proton irradiation energy on dc, small signal, and large signal rf characteristics of AlGaN/GaN high electron mobility transistors (HEMTs) were investigated. AlGaN/GaN HEMTs were irradiated with protons at fixed fluence of 5 × 1015/cm2 and energies of 5, 10, and 15 MeV. Both dc and rf characteristics revealed more degradation at lower irradiation energy, with reductions of maximum transconductance of 11%, 22%, and 38%, and decreases in drain saturation current of 10%, 24%, and 46% for HEMTs exposed to 15, 10, and 5 MeV protons, respectively. The increase in device degradation with decreasing proton energy is due to the increase in linear energy transfer and corresponding increase in nonionizing energy loss with decreasing proton energy in the active region of the HEMTs. After irradiation, both subthreshold drain leakage current and reverse gate current decreased more than 1 order of magnitude for all samples. The carrier removal rate was in the range 121–336 cm−1 over the range of proton energies employed in this study.
Highly Recurrent
TERT
Promoter Mutations in Human Melanoma
Authors: Huang Franklin W. , Hodis Eran , Xu Mary Jue , Kryukov Gregory V. , Chin Lynda , Garraway Levi A.
Published: January 2013

Promoter Mutations and Cancer

Cancer genome sequencing projects have highlighted the pathogenic role of recurrent mutations within the protein-coding regions of genes. Now, two studies suggest that the scope of mutations in human tumors extends to gene regulatory regions. In a study of 70 melanomas,

Huang
et al.

(p.
957
, published online 24 January) found that 71% harbored one of two specific mutations in the promoter region of
TERT
, the gene coding for the catalytic subunit of telomerase, the enzyme that caps chromosome ends. Independently,

Horn
et al.

(p.
959
, published online 24 January) identified a disease-segregating germline mutation in the
TERT
promoter in a family predisposed to melanoma and found additional
TERT
promoter mutations in a high percentage of sporadic melanomas and melanoma cell lines. The mutations in both studies generated new binding sites for specific transcription factors and, in reporter assays, caused an increase in transcription.
Crystalline Inorganic Frameworks with 56-Ring, 64-Ring, and 72-Ring Channels
Authors: Lin Hsin-Yau , Chin Chih-Yuan , Huang Hui-Lin , Huang Wen-Yen , Sie Ming-Jhe , Huang Li-Hsun , Lee Yuan-Han , Lin Chia-Her , Lii Kwang-Hwa , Bu Xianhui , Wang Sue-Lein
Published: January 2013

Crystalline Pores Writ Large

Porous inorganic materials are often made by using molecular templates that help to maintain internal channels during synthesis. The success with small molecules for creating microporous zeolites and related materials with angstrom-scale channels has been extended with molecular assemblies such as vesicles being used to create mesoporous materials with nanometer-scale channels. However, the walls of these materials are usually amorphous.

Lin
et al.

(p.
811
, published online 24 January) now report that crystalline mesoporous gallium zincophosphites can be made with very large channels (up to 72-membered rings spanning 3.5 nanometers) by using long-chain amine templates. The materials have limited thermal stability that hinders template removal, but when appropriately doped and loaded with chromophores, the materials exhibit broadband photoluminescence.
Coherence and Indistinguishability of Single Electrons Emitted by Independent Sources
Authors: Bocquillon E. , Freulon V. , Berroir J.-M , Degiovanni P. , Plaçais B. , Cavanna A. , Jin Y. , Fève G.
Published: January 2013

Interfering Single Electrons

Quantum information processing requires the generation of indistinguishable and coherent particles. While these have been demonstrated for photons, carrying it over for electrons and the possibility of quantum electronic implementations has been challenging. Using two independent single-electron sources patterned into a two-dimensional electron gas,

Bocquillon
et al.

(p.
1054
, published online 24 January; see the Perspective by

Schönenberger

) performed single-electron interference experiments. The results demonstrate that the generated electrons can possess the desired properties for potential quantum applications.
Genomic Analysis of Non-
NF2
Meningiomas Reveals Mutations in
TRAF7
,
KLF4
,
AKT1
, and
SMO
Authors: Clark Victoria E. , Erson-Omay E. Zeynep , Serin Akdes , Yin Jun , Cotney Justin , Özduman Koray , Avşar Timuçin , Li Jie , Murray Phillip B. , Henegariu Octavian , Yilmaz Saliha , Günel Jennifer Moliterno , Carrión-Grant Geneive , Yılmaz Baran , Grady Conor , Tanrıkulu Bahattin , Bakırcıoğlu Mehmet , Kaymakçalan Hande , Caglayan Ahmet Okay , Sencar Leman , Ceyhun Emre , Atik A. Fatih , Bayri Yaşar , Bai Hanwen , Kolb Luis E. , Hebert Ryan M. , Omay S. Bulent , Mishra-Gorur Ketu , Choi Murim , Overton John D. , Holland Eric C. , Mane Shrikant , State Matthew W. , Bilgüvar Kaya , Baehring Joachim M. , Gutin Philip H. , Piepmeier Joseph M. , Vortmeyer Alexander , Brennan Cameron W. , Pamir M. Necmettin , Kılıç Türker , Lifton Richard P. , Noonan James P. , Yasuno Katsuhito , Günel Murat
Published: January 2013

Genetic Clues to Meningioma

Meningiomas are the most common primary brain tumors in adults. Located within the layer of tissue covering the brain, these tumors are usually slow-growing and benign but can cause serious neurological complications. About half of these tumors have mutations in the
neurofibromin 2
gene (
NF2
). To identify other genes that contribute to meningioma pathogenesis,

Clark
et al.

(p.
1077
, published online 24 January) performed genome sequence analysis on 300 tumors. Meningiomas fell into two general classes: benign tumors located at the skull base—which tend to harbor mutations in the
TRAF7, KLF4, AKT1
, and
SMO
genes—and higher-grade tumors located in the cerebral and cerebellar hemispheres harbor mutations in
NF2.
Draft Genome Sequence of Fructophilic Lactobacillus florum
Authors: Kim Eun Bae , Tyler Charlotte A. , Kopit Lauren M. , Marco Maria L.
Published: January 2013

Herein we report the first genome sequence for
Lactobacillus florum
.
L. florum
2F was isolated from Valencia orange leaves and is fructophilic, like other strains of this species. The draft genome of
L. florum
2F contains 1,261,842 bp with a
G+C
content of 41.5% in 46 contigs (≥500 bp).
Draft Genome Sequence of Rhizobium mesoamericanum STM3625, a Nitrogen-Fixing Symbiont of
Mimosa pudica
Isolated in French Guiana (South America)
Authors: Moulin Lionel , Mornico Damien , Melkonian Rémy , Klonowska Agnieszka
Published: January 2013

Rhizobium mesoamericanum
STM3625 is a
Mimosa pudica
symbiont isolated in French Guiana. This strain serves as a model bacterium for comparison of adaptation to mutualism (symbiotic traits, bacterial genetic programs for plant infection) between alpha and beta rhizobial symbionts of
Mimosa pudica
.
Draft Genome Sequence of
Methanobacterium
sp. Maddingley, Reconstructed from Metagenomic Sequencing of a Methanogenic Microbial Consortium Enriched from Coal-Seam Gas Formation Water
Authors: Rosewarne Carly P. , Greenfield Paul , Li Dongmei , Tran-Dinh Nai , Midgley David J. , Hendry Philip
Published: January 2013

The draft genome of
Methanobacterium
sp. Maddingley was reconstructed from metagenomic sequencing of a methanogenic microbial consortium enriched from coal-seam gas formation water. It is a hydrogenotrophic methanogen predicted to grow using hydrogen and carbon dioxide.
Aborted sudden cardiac death (SCD) in a patient with hypertrophic cardiomyopathy (HCM) with low-risk factors for SCD
Authors: Kaushik Sashank , Subramanian Stalin Ramakrishnan , Rafii Shahrokh , Castillo Ricardo
Published: January 2013

Remarkable advancements have been made in understanding the pathophysiology of hypertrophic cardiomyopathy (HCM), since the first implantable cardioverter defibrillator (ICD) was placed in a human, more than 25 years ago to prevent sudden cardiac death (SCD). ICD has become the cornerstone in the management of HCM, with an ability to change the natural course of this complex disease. American College of Cardiology/American Heart Association guidelines have been charted out to help risk stratify asymptomatic or minimally symptomatic adults with HCM, in order to prevent SCD in such individuals. Our patient with left ventricular outflow tract  gradient <30 mm Hg, left ventricular  wall thickness < 30 mm, negative medical history of syncope and no family history of SCD, would have been at low risk for SCD.
Immunocompetent young man with cerebral abscess and cortical venous infarction mimicking cerebritis caused byGemella morbillorum
Authors: Milnik Annette , Gazis Angelos , Tammer Ina , Bartels Claudius
Published: January 2013

Gemella morbillorumis an anaerobic gram-positive diplococcus and in most cases a harmless commensal, which occasionally causes infections in the central nervous system. We report on an immunocompetent young man with focal neurological symptoms and cephalgia caused by a cerebral abscess. Although successful treatment was done with neurosurgical intervention and antibiotic therapy, he suffered from a venous infarction 5 weeks after first diagnosis, which mimicked cerebritis as an early stage of relapsing abscess. Imaging and investigation of cerebrospinal fluid was necessary for sufficient differential diagnosis and antibiotic therapy could be stopped after altogether 8 weeks of treatment. In summary,G morbillorumcauses not only biphasic infections, but also can be accompanied by infarction in the central nervous system despite sufficient antibiotic therapy.
Acute stroke in a patient with advanced uraemia: should thrombolysis be given?
Authors: McCloskey Marguerite , Masengu Agnes , Shields Joanne , Wiggam M Ivan
Published: January 2013

A 65-year-old gentleman with stage 5 chronic kidney disease developed an acute posterior circulation stroke, which was treated with intravenous thrombolytic therapy. This was complicated by a retroperitoneal haemorrhage. The patient made an excellent neurological recovery and was discharged to home, independently mobile, having been established on haemodialysis. This case highlights the challenges of managing acute ischaemic stroke in patients with advanced uraemia.
Platypnea-Orthodeoxia syndrome after repair of a paraesophageal hernia
Authors: Vallurupalli Sunil , Lodha Ankur , Kupfer Yizhak , Tessler Sidney
Published: January 2013

The Platypnea-Orthodeoxia syndrome is characterised by dyspnoea and deoxygenation accompanying a change from the recumbent to the upright position. An 81-year-old woman had an elective paraesophageal hernia repair. She developed dyspnoea and hypoxemia post-operatively that was worse when upright. An agitated saline echocardiogram revealed a right-to-left shunt through a patent foramen ovale that increased when the patient was upright. Over 3 weeks the patients’ shunt, dyspnoea and hypoxemia improved and she was discharged home.
Enteric adenocarcinoma lung: a rare presentation in an Omani woman
Authors: Qureshi Asim , Furrukh Muhammad
Published: January 2013

Pulmonary adenocarcinoma is a common neoplasm, yet the one with enteric or intestinal differentiation poses a diagnostic challenge to pathologists as it shares a common immunohistochemical profile with metastatic colorectal carcinoma. We report a case of a 61-year-old woman. She was on surveillance when incidentally she was discovered to have multiple bilateral lung nodules on imaging; the largest was surgically removed for histological examination. Morphology was consistent with a moderately differentiated adenocarcinoma .The tumour cells were positive for cytokeratin (CK) 7, CDX2, CK20 and were negative for thyroid transcription factor 1. The morphology and immune histochemical profile raised the differential diagnosis of a metastatic colorectal carcinoma and a primary lung adenocarcinoma with enteric differentiation. On the basis of morphology and CK7 positivity we established the diagnosis of enteric-type adenocarcinoma of primary lung origin. She has completed planned courses of palliative chemotherapy and remains on surveillance.
A child with a long-standing, intensely itching subcutaneous nodule on a thigh: an uncommon (?) reaction to commonly used vaccines
Authors: Bergfors Elisabet , Lundmark Katarzyna , Nyström Kronander Ulla
Published: January 2013

A 2-year-old girl presented with an intensely itching subcutaneous nodule on the front of a thigh. The nodule persisted for 10 months until it was excised. Subsequent investigation for malignancy and systemic disease showed no pathological findings. The diagnosis, persistent itching vaccination granuloma, was revealed by hazard almost 2 years after the onset of symptoms. Persistent itching subcutaneous nodules at the injection site for aluminium containing vaccines (mostly diphtheria-tetanus-pertussis combination vaccines for primary immunisation of infants) may appear with a long delay after the vaccination (months), cause prolonged itching (years) and are often associated with contact allergy to aluminium. The condition is poorly recognised in Health Care which may lead to prolonged symptoms and unnecessary investigations.
Primary abdominal nocardiosis masquerading as tubercular pelvic inflammatory disease in an immunocompetent individual
Authors: Naha Kushal , Dasari Sowjanya , Vivek G , Prabhu Mukhyaprana
Published: January 2013

We report the case of a 30-year-old housewife who presented with fever and lower abdominal pain, and was diagnosed with an adnexal collection. Initial evaluation was suggestive of tubercular pelvic inflammatory disease (PID). Subsequently, from a culture of pus aspirated from the collection grew out Nocardia species. She was treated with amikacin and cotrimoxazole and made a complete recovery. Clinical and laboratory evaluation for immunosuppression was negative. Primary abdominal nocardiosis is an unusual cause for PID and an important differential diagnosis for tuberculosis.
Combined infection of vertebroplasty and aortic graft after intravesical BCG treatment
Authors: Santbergen Bart , Vriens P H W E , de Lange W C M , Van Kasteren M E E
Published: January 2013

We report a 58-year-old man with spondylodiscitis byMycobacterium bovis-BCG3 years after intravesical BCG treatment, and shortly after a vertebroplasty. Further examination showed a psoas abscess and oedema around an endovascular aortic graft, which had been placed 1 year earlier. Puncture of the psoas abscess also grewM bovis-BCG. The patient recovered with a combination of antituberculous treatment and surgery. With hindsight a mycotic aneurysm had been present at the time of aortic graft placement and spondylodiscitis at the time of vertebroplasty. This case shows that low grade and longstanding infections may occur following intravesical BCG installation.
Acute myocardial infarction and heart block: a challenge to emergency physicians
Authors: Bacci Marcelo Rodrigues , Santos Janaina Aparecida Boide , Nogueira Leonardo Fernando Ferrari , Namura José Jorge
Published: January 2013

We present the case of a patient who underwent an acute ST-elevation myocardial infarction of the inferior wall and transitory total heart block in the first hours of his clinical presentation. There was no haemodynamic instability before the thrombolytic therapy was performed 8 h after the onset of pain. There was no block recurrence. The current case shows a possible complication during the thrombolytic therapy and the urge for a quick decision by the emergency physician. Pacemaker implantation should be considered in the event of the patient's haemodynamic worsening once the success of the therapy is a reflex of the arrhythmia reversion most of the times.
Near-fatal small bowel ischaemia secondary to sacrocolpopexy mesh
Authors: Vulliamy Paul , Berner Alison May , Farooq Muhammad Suleman , Srilekha Attavar
Published: January 2013

A 74-year-old woman presenting with acute abdominal pain underwent surgery for suspected small bowel ischaemia. At laparotomy, a sacrocolpopexy mesh in the pelvis, which had been inserted 8 years previously, was found to be causing strangulation of a 2-m length of the small bowel. Following resection and primary anastomosis, the patient spent several days in intensive care before her eventual discharge. This unusual life-threatening complication should be considered in patients presenting with abdominal pain even many years following abdominal sacrocolpopexy.
Catastrophic osteomyelitis following percutaneous wire fixation of a distal radial fracture: a cautionary tale of poor patient selection followed by surgical mishap
Authors: Shields David W , Elson David W , Marsh Martin , Gray Andrew C
Published: January 2013

We present a case of distal radius fracture. Several sequential unfortunate events resulted in a poor outcome. The patient was poorly selected because the degree of early dementia was not fully appreciated, due to intermittent periods of lucidity. Having elected to treat this distal radius fracture with Kirschner wires, a wire snapped during the procedure and was deemed safe to leave within the medullary cavity. Subsequently, the patient was left in a cast for 4 weeks without regular pin site inspection. When the cast was removed a gross osteomyelitis had developed. This series of events, led to unnecessary morbidity and extended the immobilisation time with reduced wrist function. This case highlights the importance of careful patient selection, surgical tactics and continuity of care.
Reversible cerebral vasoconstriction syndrome and bilateral vertebral artery dissection presenting in a patient after cesarean section
Authors: Mitchell Lex A , Santarelli Justin G , Singh Inder Paul , Do Huy M
Published: January 2013

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden-onset thunderclap headache and focal neurologic deficits. Once thought to be a rare syndrome, more advanced non-invasive imaging has led to an increase in RCVS diagnosis. Unilateral vertebral artery dissection has been described in fewer than 40% of cases of RCVS. Bilateral vertebral artery dissection has rarely been reported. We describe the case of a patient with RCVS and bilateral vertebral artery dissection presenting with an intramedullary infarct treated successfully with medical management and careful close follow-up. This rare coexistence should be recognized as the treatment differs.
Features and predictors of myocardial injury in carbon monoxide poisoned patients
Authors: Cha Yong Sung , Cha Kyoung Chul , Kim Oh Hyun , Lee Kang Hyun , Hwang Sung Oh , Kim Hyun
Published: January 2013

Background and purpose

By contrast with neurologic injury, myocardial injury associated with carbon monoxide (CO) poisoning has not been well investigated. Therefore, this study assessed features and predictors of myocardial injury in CO poisoned patients.

Subjects and methods

250 CO poisoning cases that were diagnosed and treated by the emergency department of Wonju Christian Hospital from January 2006 to February 2012 were retrospectively reviewed.

Results

Fifty (20%) out of 250 patients with CO poisoning developed myocardial injury. Among those with elevated troponin I (Tn I), peak levels occurred at 11.0 (IQR, 4.5–18.5) h normalising by 65.0 (IQR 44.0–96.0) h. CO exposure time, and total and ICU admission length was longer (7.5 (IQR 3.7–10.0) h vs 3.0 (IQR 1.0–7.5) h, p<0.001; 3.5 (IQR 0.0–7.0) days and 0.0 (IQR 0.0–1.25) days vs 0.0 (IQR 0.0–2.0) days and 0.0 (IQR 0.0–0.0) days, p<0.001, respectively) in the myocardial vs non-myocardial injury group. The predictors of myocardial injury were male gender, Glasgow Coma Scale (GCS) ≤14, and CO exposure time ≥2 h (OR (95% CI) of 3.341 (1.171 to 9.531), 9.920 (3.763 to 26.150), and 7.743 (1.610 to 37.238), respectively).

Conclusions

Myocardial injury developed in 20% of CO poisoned patients. Time to normalisation and of peak Tn I level in elevated Tn I group was 65.0 (IQR 44.0–96.0) h and 11.0 (IQR 4.5–18.5) h. Presence of myocardial injury was associated with poorer prognosis. Predictors of myocardial injury included male gender, GCS of 14 or less, or CO exposure times greater than 2 h.
The physiological and pathophysiological roles of adipocyte miRNAs
Authors: Ling Hongyan , Li Xing , Yao Chao Hua , Hu Bi , Liao Duanfang , Feng Shuidong , Wen Gebo , Zhang Liang
Published: January 2013

MicroRNAs (miRNAs) are highly conserved, small, noncoding RNAs that regulate gene expression at the posttranscriptional level. Their actions affect numerous important biological processes, including adipocyte differentiation and function, sugar and lipid metabolism, and insulin production and secretion. Recent reports suggest miRNAs may also be involved in the pathogenic processes of obesity, diabetes, and insulin resistance. In this review, we summarize research progresses on adipocyte miRNAs and their physiological and pathological implications.
Research on DNA methylation of human osteosarcoma cell MGMT and its relationship with cell resistance to alkylating agents
Authors: Guo Jun , Cui Qiu , Jiang WeiHao , Liu Cheng , Li DingFeng , Zeng Yanjun
Published: January 2013

The objective of this study was to explore the O6-methylguanine-DNA methyltransferase (MGMT) gene methylation status and its protein expression, as well as the effects of demethylating agent 5-Aza-2′-deoxycytidine (5-Aza-CdR) on MGMT gene expression and its resistance to alkylating agents, and to elucidate MGMT expression mechanism and significance in osteosarcoma. The human osteosarcoma cell lines Saos-2 and MG-63 were collected and treated with 5-Aza-CdR for 6 days. The cells not treated with 5-Aza-CdR were set as a negative control. The genomic DNA was extracted from the Saos-2 and MG-63 cells using methylation-specific PCR to detect the promoter CpG island methylation status of the MGMT gene. Cell sensitivity to alkylating agents before and after drug administration was detected by the MTT method. The variation in MGMT gene mRNA and protein was detected by reverse transcription PCR (RT–PCR) and Western blotting. The MGMT promoter gene of normal Saos-2 cells was methylated, with reduced MGMT mRNA and protein expression; the MGMT mRNA and protein expression of Saos-2 cells treated with 5-Aza-CdR was obviously enhanced, and its sensitivity to alkylating agents was reversed. Meanwhile, with promoter CpG island unmethylation of the MGMT gene, MGMT protein was expressed in the normal MG-63 cells and the MG-63 cells treated with 5-Aza-CdR, and both showed resistance to alkylating agents. The methylation status of the MGMT gene promoter in human osteosarcoma cells reflected the cells’ ability to induce MGMT protein expression and can be used as a molecular marker to project the sensitivity of cancer tissues to alkylating agent drugs.
The spectroscopic NMR analysis of 2-dicyanovinyl-5-phenylthiophene by the density functional method
Authors: Li Xiao-Hong , Zhang Xian-Zhou
Published: January 2013

Quantum chemistry calculations have been performed by using the Gaussian03 program to compute the optimized geometry and harmonic vibrational frequency of 2-dicyanovinyl-5-phenylthiophene (C14H8N2S) in the ground state. Atomic charges at B3LYP/6-311++G(d,p) level are also calculated. Potential energy distributions (PEDs) using MOLVIB program are also used to interpret the theoretical vibrational spectra of the title compound. A detailed interpretation of the infrared spectra of the title compound is reported. The theoretical spectrograms for the IR spectra of the title compound have been constructed. The crystal structure obtained by molecular mechanics belongs to the P21space group, with lattice parameters Z = 2, a = 6.6745 Å, b = 14.7672 Å, c = 11.0986 Å, ρ = 0.921 g cm–3. In addition, the13C and1H NMR are further investigated by the B3LYP/6-311++G(d,p) and B3LYP/6-311++G(2d,2p) methods.
Rauisuchia
Authors: Nesbitt Sterling J. , Brusatte Stephen L. , Desojo Julia B. , Liparini Alexandre , De França Marco A. G. , Weinbaum Jonathan C. , Gower David J.
Published: January 2013

‘Rauisuchia’ comprises Triassic pseudosuchians that ranged greatly in body size, locomotor styles and feeding ecologies. Our concept of what constitutes a rauisuchian is changing as a result of discoveries over the last 15 years. New evidence has shown that rauisuchians are probably not a natural (monophyletic) group, but instead are a number of smaller clades (e.g. Rauisuchidae, Ctenosauriscidae, Shuvosauridae) that may not be each other's closest relatives within Pseudosuchia. Here, we acknowledge that there are still large gaps in the basic understanding in the alpha-level taxonomy and relationships of these groups, but good progress is being made. As a result of renewed interest in rauisuchians, an expanding number of recent studies have focused on the growth, locomotor habits, and biomechanics of these animals, and we review these studies here. We are clearly in the midst of a renaissance in our understanding of rauisuchian evolution and the continuation of detailed descriptions, the development of explicit phylogenetic hypotheses, and explicit palaeobiological studies are essential in advancing our knowledge of these extinct animals.
A simplified method for determining phenotypic traits in patients with obstructive sleep apnea
Authors: Wellman Andrew , Edwards Bradley A. , Sands Scott A. , Owens Robert L. , Nemati Shamim , Butler James , Passaglia Chris L. , Jackson Andrew C. , Malhotra Atul , White David P.
Published: January 2013

We previously published a method for measuring several physiological traits causing obstructive sleep apnea (OSA). The method, however, had a relatively low success rate (76%) and required mathematical modeling, potentially limiting its application. This paper presents a substantial revision of that technique. To make the measurements, continuous positive airway pressure (CPAP) was manipulated during sleep to quantify 1) eupneic ventilatory demand, 2) the level of ventilation at which arousals begin to occur, 3) ventilation off CPAP (nasal pressure = 0 cmH2O) when the pharyngeal muscles are activated during sleep, and 4) ventilation off CPAP when the pharyngeal muscles are relatively passive. These traits could be determined in all 13 participants (100% success rate). There was substantial intersubject variability in the reduction in ventilation that individuals could tolerate before having arousals (difference between ventilations #1 and #2 ranged from 0.7 to 2.9 liters/min) and in the amount of ventilatory compensation that individuals could generate (difference between ventilations #3 and #4 ranged from −0.5 to 5.5 liters/min). Importantly, the measurements accurately reflected clinical metrics; the difference between ventilations #2 and #3, a measure of the gap that must be overcome to achieve stable breathing during sleep, correlated with the apnea-hypopnea index ( r = 0.9, P < 0.001). An additional procedure was added to the technique to measure loop gain (sensitivity of the ventilatory control system), which allowed arousal threshold and upper airway gain (response of the upper airway to increasing ventilatory drive) to be quantified as well. Of note, the traits were generally repeatable when measured on a second night in 5 individuals. This technique is a relatively simple way of defining mechanisms underlying OSA and could potentially be used in a clinical setting to individualize therapy.
Differential effects of aging and exercise on intra-abdominal adipose arteriolar function and blood flow regulation
Authors: Davis Robert T. , Stabley John N. , Dominguez James M. , Ramsey Michael W. , McCullough Danielle J. , Lesniewski Lisa A. , Delp Michael D. , Behnke Brad J.
Published: January 2013

Adipose tissue (AT), which typically comprises an increased percentage of body mass with advancing age, receives a large proportion of resting cardiac output. During exercise, an old age-associated inability to increase vascular resistance within the intra-abdominal AT may compromise the ability of the cardiovascular system to redistribute blood flow to the active musculature, contributing to the decline in exercise capacity observed in this population. We tested the hypotheses that 1) there would be an elevated perfusion of AT during exercise with old age that was associated with diminished vasoconstrictor responses of adipose-resistance arteries, and 2) chronic exercise training would mitigate the age-associated alterations in AT blood flow and vascular function. Young (6 mo; n = 40) and old (24 mo; n = 28) male Fischer 344 rats were divided into young sedentary (YSed), old sedentary (OSed), young exercise trained (YET), or old exercise trained (OET) groups, where training consisted of 10-12 wk of treadmill exercise. In vivo blood flow at rest and during exercise and in vitro α-adrenergic and myogenic vasoconstrictor responses in resistance arteries from AT were measured in all groups. In response to exercise, there was a directionally opposite change in AT blood flow in the OSed group (∼150% increase) and YSed (∼55% decrease) vs. resting values. Both α-adrenergic and myogenic vasoconstriction were diminished in OSed vs. YSed AT-resistance arteries. Exercise training resulted in a similar AT hyperemic response between age groups during exercise (YET, 9.9 ± 0.5 ml·min−1·100−1 g; OET, 8.1 ± 0.9 ml·min−1·100−1 g) and was associated with enhanced myogenic and α-adrenergic vasoconstriction of AT-resistance arteries from the OET group relative to OSed. These results indicate that there is an inability to increase vascular resistance in AT during exercise with old age, due, in part, to a diminished vasoconstriction of AT arteries. Furthermore, the results indicate that exercise training can augment vasoconstriction of AT arteries and mitigate age-related alterations in the regulation of AT blood flow during exercise.
The Insulin Receptor Negatively Regulates the Action of Pseudomonas Toxin-Based Immunotoxins and Native Pseudomonas Toxin
Authors: Liu Xiu Fen , FitzGerald David J. , Pastan Ira
Published: January 2013

SS1P is a recombinant immunotoxin composed of an antimesothelin Fv fragment fused to a truncated portion of Pseudomonas exotoxin A. SS1P targets and kills mesothelin-expressing tumors, which include mesothlioma as well as ovarian, lung, and pancreatic cancers. SS1P is currently in clinical trials in mesothelioma. Because insulin acting through the insulin receptor is a survival factor for many cancer cell lines, we explored how lowering insulin receptor level would affect the cytotoxic action of SS1P. We show here that siRNA knockdown of the insulin receptor enhanced the cytotoxic action of native Pseudomonas exotoxin and enhanced SS1P toxicity on several human cell lines, but did not affect the response to other cytotoxic agents such as TRAIL, etoposide, and cycloheximide. To determine how insulin receptor knockdown enhances SS1P action, we analyzed various steps involved in cell killing. We found that insulin receptor knockdown increases the cleavage of SS1P by furin, which allows more toxin to reach the cytosol and inactivate elongation factor 2. These findings indicate that the insulin receptor negatively regulates immunotoxin action. Cancer Res; 73(7); 2281–8. ©2013 AACR.
Inactivation or Loss of TTP Promotes Invasion in Head and Neck Cancer via Transcript Stabilization and Secretion of MMP9, MMP2, and IL-6
Authors: Van Tubergen Elizabeth A. , Banerjee Rajat , Liu Min , Broek Robert Vander , Light Emily , Kuo Shiuhyang , Feinberg Stephen E. , Willis Amanda L. , Wolf Gregory , Carey Thomas , Bradford Carol , Prince Mark , Worden Francis P. , Kirkwood Keith L. , D'Silva Nisha J.
Published: January 2013

Purpose: Invasion is the critical step in progression of a precancerous lesion to squamous cell carcinoma of the head and neck (HNSCC). Invasion is regulated by multiple proinflammatory mediators. Tristetraprolin (TTP) is an mRNA-degrading protein that regulates multiple proinflammatory mediators. TTP may serve as an excellent treatment target. Rap1 is a ras-like oncoprotein that induces critical signaling pathways. In this study, the role of rap1 in TTP-mediated invasion was investigated.

Experimental Design: Using complementary approaches, we modulated TTP and altered expression of interleukin (IL)-6 and matrix metalloproteinase (MMP) 2/9, which were quantified by ELISA and zymogram. Invasion was evaluated in vitro using the oral-cancer-equivalent (OCE) three-dimensional model and in vivo in the chick chorioallantoic membrane (CAM). The role of rap1 and p38 were established using knockdown strategies.

Results: Downregulation of TTP significantly increased invasion via secretion of MMP9/2 and IL-6. In the novel OCE and CAM invasion models of HNSCC, cells with downregulated TTP destroyed the basement membrane to invade the underlying connective tissue. Rap1 induces p38 mitogen-activated protein kinase (p38)-mediated inactivation of TTP. Inactive TTP enhances transcript stability via binding to the 3′-untranslated region (UTR). High IL-6 and MMP9 are prognostic for poor clinical outcomes in patients with HNSCC.

Conclusions: Targeting the rap1-p38-TTP cascade is an attractive novel treatment strategy in HNSCC to concurrently suppress multiple mediators of invasion. Clin Cancer Res; 19(5); 1169–79. ©2012 AACR.