bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Genomics of Recent Shiga Toxin-Producing Escherichia coli O104:H4: Short-Term Evolution of an Emerging Pathogen
Authors: Grad Yonatan H. , Godfrey Paul , Cerquiera Gustavo C. , Mariani-Kurkdjian Patricia , Gouali Malika , Bingen Edouard , Shea Terrence P. , Haas Brian J. , Griggs Allison , Young Sarah , Zeng Qiandong , Lipsitch Marc , Waldor Matthew K. , Weill François-Xavier , Wortman Jennifer R. , Hanage William P.
Published: January 2013

The large outbreak of diarrhea and hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing
Escherichia coli
O104:H4 in Europe from May to July 2011 highlighted the potential of a rarely identified
E. coli
serogroup to cause severe disease. Prior to the outbreak, there were very few reports of disease caused by this pathogen and thus little known of its diversity and evolution. The identification of cases of HUS caused by
E. coli
O104:H4 in France and Turkey after the outbreak and with no clear epidemiological links raises questions about whether these sporadic cases are derived from the outbreak. Here, we report genome sequences of five independent isolates from these cases and results of a comparative analysis with historical and 2011 outbreak isolates. These analyses revealed that the five isolates are not derived from the outbreak strain; however, they are more closely related to the outbreak strain and each other than to isolates identified prior to the 2011 outbreak. Over the short time scale represented by these closely related organisms, the majority of genome variation is found within their mobile genetic elements: none of the nine O104:H4 isolates compared here contain the same set of plasmids, and their prophages and genomic islands also differ. Moreover, the presence of closely related HUS-associated
E. coli
O104:H4 isolates supports the contention that fully virulent O104:H4 isolates are widespread and emphasizes the possibility of future food-borne
E. coli
O104:H4 outbreaks.

IMPORTANCE
In the summer of 2011, a large outbreak of bloody diarrhea with a high rate of severe complications took place in Europe, caused by a previously rarely seen
Escherichia coli
strain of serogroup O104:H4. Identification of subsequent infections caused by
E. coli
O104:H4 raised questions about whether these new cases represented ongoing transmission of the outbreak strain. In this study, we sequenced the genomes of isolates from five recent cases and compared them with historical isolates. The analyses reveal that, in the very short term, evolution of the bacterial genome takes place in parts of the genome that are exchanged among bacteria, and these regions contain genes involved in adaptation to local environments. We show that these recent isolates are not derived from the outbreak strain but are very closely related and share many of the same disease-causing genes, emphasizing the concern that these bacteria may cause future severe outbreaks.
Five New Genes Are Important for Common Polysaccharide Antigen Biosynthesis in Pseudomonas aeruginosa
Authors: Hao Youai , King Jerry D. , Huszczynski Steven , Kocíncová Dana , Lam Joseph S.
Published: January 2013

Common polysaccharide antigen (CPA) is a conserved cell surface polysaccharide produced by
Pseudomonas aeruginosa
. It contains a rhamnan homopolymer and is one of the two forms of O polysaccharide attached to
P. aeruginosa
lipopolysaccharide (LPS). Our laboratory has previously characterized an eight-gene cluster (
pa5447-pa5454
in
P. aeruginosa
PAO1) required for biosynthesis of CPA. Here we demonstrate that an adjacent five-gene cluster
pa5455-pa5459
is also involved. Using reverse transcriptase PCR (RT-PCR), we showed that the original eight-gene cluster and the new five-gene cluster are both organized as operons. We have analyzed the LPS phenotypes of in-frame deletion mutants made in each of the five genes, and the results verified that these five genes are indeed required for CPA biosynthesis, extending the CPA biosynthesis locus to contain 13 contiguous genes. By performing overexpression experiments of different sets of these biosynthesis genes, we were able to obtain information about their possible functions in CPA biosynthesis.

IMPORTANCE
Lipopolysaccharide (LPS) is an important cell surface structure of Gram-negative bacteria. The human opportunistic pathogen
Pseudomonas aeruginosa
simultaneously produces an O-antigen-specific (OSA) form and a common polysaccharide antigen (CPA) form of LPS. CPA, the focus of this study, is composed of α-1-2, α1-3-linked
d
-rhamnose sugars and has been shown to be important for attachment of the bacteria to human airway epithelial cells. Genome sequencing of this species revealed a new five-gene cluster that we predicted to be involved in CPA biosynthesis and modification. In this study, we have generated chromosomal knockouts by performing in-frame deletions and allelic replacements. Characterizing the function of each of the five genes is important for us to better understand CPA biosynthesis and the mechanisms of chain length termination and regulation of this unique D-rhamnan polysaccharide.
Successful rechallenge with clozapine following ‘red alert’
Authors: Toni-Uebari Thelma K , Rees John
Published: January 2013

A case is presented of a 23-year-old lady with treatment-resistant schizoaffective disorder who had responded well to treatment with clozapine. Fifteen months after satisfactory use of clozapine she had ‘red alerts’ from routine haematological monitoring indicating neutropenia. Clozapine was discontinued and she was admitted to the psychiatric hospital to manage the aftermath of discontinuing clozapine and start alternative treatment with other antipsychotics. Her mental health rapidly deteriorated. Adequate trials with amisulpride, haloperidol, olanzapine and flupenthixol decanoate yielded little improvement in her clinical state. After 9 months of non-response to other antipsychotic medications, she was rechallenged with clozapine, followed by improvement in her mental state. She was eventually discharged home after 14 months of hospitalisation in a stable mental state. She remained mentally stable in the community on clozapine for 18 months after rechallenge, with no further red alerts.
An unexpected CT finding in a patient with abdominal pain
Authors: Lim Jeffrey , Phillips Alexander W , Thomson Wendy L
Published: January 2013

A fit and well 16-year-old girl presented to the emergency department with signs and symptoms suggestive of appendicitis. A transabdominal ultrasound scan revealed a normal appendix but there was significant free fluid in the pelvis. Consequently, a CT scan of her abdomen was performed which showed mucosal oedema and inflammation involving virtually the entire length of her large bowel (the ‘accordion sign’).Clostridium difficilecolitis was thus suspected; however, the toxin was not detected in her stool. The patient was treated conservatively with intravenous fluids and antibiotics and had an uneventful recovery. She was subsequently discharged home 3 days later with a full recovery. In this case, the radiological appearance of the accordion sign which is traditionally known to be pathognomonic of pseudomembranous colitis, reveals that it may also be indicative of severe colonic luminal inflammation.
Plantaris rupture: why is it important?
Authors: Rohilla Seema , Jain Nitin , Yadav Rohtas
Published: January 2013

Plantaris muscle is accessory plantar flexor of calf, a vestigial muscle of triceps surae complex. Its importance lies in the fact that its rupture cans mimic deep vein thrombosis (DVT). Sometimes when there is rupture of Achilles tendon, intact plantaris can still cause plantar flexion at ankle presenting a confusing picture. We present one such case of plantaris rupture confused by radiology resident with DVT. A 51-year-old man had a feeling as if kicked in back of calf along with a snapping sound and severe pain while playing tennis. On seeing fluid between muscle plane and a hypoechoic structure radiology resident labelled it DVT. MRI suggested ruptured plantaris as fluid and muscle stump were seen between gastronemius and soleus. Patient was treated conservatively with rest, ice compression and elevated leg and showed significant reduction in pain and swelling.
Clozapine-induced ischaemic colitis
Authors: Shah Veer , Anderson Jacqueline
Published: January 2013

Ischaemic colitis is a rare side effect of antipsychotics, especially phenothiazines and atypical antipsychotics. The colitis may be precipitated secondary to the anticholinergic effects of such medication rather than a direct cytotoxic effect of the drugs themselves. A 32-year-old man with a history of schizophrenia was admitted to the hospital with a history of diffuse abdominal pain and vomiting. His bloods showed leucocytosis. Sigmoidoscopy demonstrated rectal sparing acute colitis, confirmed on biopsy findings. A CT scan also showed similar findings. After careful drug review, it was decided that clozapine was the cause of colitis and promptly stopped. The patient was managed conservatively on intravenous fluids and antibiotics and made a full recovery. Any patient starting antipsychotics should be counselled on their anticholinergic side effects. Drugs should always be considered as a cause of ischaemic colitis; although an uncommon complication of antipsychotics, it can have a potentially fatal outcome.
Pseudomembranous colitis due toClostridium difficileas a cause of perineal necrotising fasciitis
Authors: Duburcq Thibault , Parmentier-Decrucq Erika , Poissy Julien , Mathieu Daniel
Published: January 2013

Although rare, pseudomembranous colitis may be a cause of perineal necrotising fasciitis in a context of immunosuppression, as in the case we report. This origin must be quickly identified because the therapeutic management, especially surgery, is unlikely to be the same as usual. Similarly, antibiotic treatment is also a matter of discussion due to the potential deleterious role of antibiotics in pseudomembranous colitis.
Effects of cadmium on the actin cytoskeleton in renal mesangial cells
Authors: Templeton Douglas M. , Liu Ying
Published: January 2013

We provide an overview of our studies on cadmium and the actin cytoskeleton in mesangial cells, from earlier work on the effects of Cd2+on actin polymerization in vivo and in vitro, to a role of disruption or stabilization of the cytoskeleton in apoptosis and apoptosis-like death. More recent studies implicate cadmium-dependent association of gelsolin and the Ca2+/calmodulin-dependent protein kinase II (CaMK-II) with actin filaments in cytoskeletal effects. We also present previously unpublished data concerning cadmium and the disruption of focal adhesions. The work encompasses studies on rat, mouse, and human mesangial cells. The major conclusions are that Cd2+acts independently of direct effects on cellular Ca2+levels to nevertheless activate Ca2+-dependent proteins that shift the actin polymerization–depolymerization in favour of depolymerization. Cadmium-dependent translocation of CaMK-IIδ, gelsolin, and a 50 kDa gelsolin cleavage fragment to the filamentous (F-)actin cytoskeleton appear to be involved. An intact filamentous actin cytoskeleton is required to initiate apoptotic and apoptotic-like death, but F-actin depolymerization is an eventual result.
LEPTONIC DECAY OF HEAVY–LIGHT MESONS IN A QCD POTENTIAL MODEL
Authors: PATHAK KRISHNA KINGKAR , CHOUDHURY D. K. , BORDOLOI N. S.
Published: January 2013

We study the masses and decay constants of heavy–light flavor mesons D, Ds, B and Bs in a QCD potential model. The mesonic wave function is used to compute the masses of D and B mesons in the ground state and the wave function is transformed to momentum space to estimate the pseudoscalar decay constants of these mesons. The leptonic decay widths and branching ratio of these mesons for different leptonic channels are also computed to compare with the experimental values. The results are found to be compatible with available data.
MAGNETIZATION MEASUREMENTS IN THE 80 K TRANSFORMATION FOR DEUTERATED ORGANIC SUPERCONDUCTOR κ-(BEDT-TTF)2Cu[N(CN)2]Br
Authors: EL OUADDI H. , TIRBIYINE A. , TAOUFIK A. , RAMZI A. , HAFID A. , NAFIDI A. , CHAIB H. , SENOUSSI S.
Published: January 2013

In this paper, we report systematic magnetic measurements on deuterated organic superconductor (κ- D 8- Br )κ-( BEDT - TTF )2 Cu [ N ( CN )2] Br . The irreversibility line H irr (T) and the critical current density Jc were studied. Our results show the strong dependence of H irr (T) and Jc on the cooling rate. The structural transformation which occurs at the vicinity of 80 K very strongly influences the physics of vortex lattice and the associated magnetic behavior. The irreversible magnetization becomes null at H irr and vortices are not pinned; therefore they can displace more freely for an increase of the field or the temperature.
Piezoelectric Microfiber Composite Actuators for Morphing Wings
Authors: Usher Timothy D. , Ulibarri Kenneth R. , Camargo Gilberto S.
Published: January 2013

Morphing wing technologies provide expanded functionality in piloted and robotic aircraft, extending particular vehicle mission parameters as well as increasing the role of aviation in both military and civilian applications. However, realizing control surfaces that do not void the benefits of morphing wings presents challenges that can be addressed with microfiber composite actuators (MFCs). We present two approaches for realizing control surfaces. In one approach, flap-like structures are formed by bonding MFCs to each side of a metal substrate. In the other approach, MFCs are bonded directly to the wing. Counter intuitively, the flap approach resulted in larger voltage actuation curvatures, with increased mass load. Actuation performance, defined as the ratio of curvature per applied voltage, was as large as 5.8±0.2×10−4 (kV·mm)−1. The direct bonding approach reveals that at zero wing pressure, up to 63±3 μm of displacement could be realized.
Mental and Physical Health and Intimate Partner Violence against Women: A Review of the Literature
Authors: Dillon Gina , Hussain Rafat , Loxton Deborah , Rahman Saifur
Published: January 2013

Associations between intimate partner violence (IPV) and poor physical and mental health of women have been demonstrated in the international and national literature across numerous studies. This paper presents a review of the literature on this topic. The 75 papers included in this review cover both original research studies and those which undertook secondary analyses of primary data sources. The reviewed research papers published from 2006 to 2012 include quantitative and qualitative studies from Western and developing countries. The results show that while there is variation in prevalence of IPV across various cultural settings, IPV was associated with a range of mental health issues including depression, PTSD, anxiety, self-harm, and sleep disorders. In most studies, these effects were observed using validated measurement tools. IPV was also found to be associated with poor physical health including poor functional health, somatic disorders, chronic disorders and chronic pain, gynaecological problems, and increased risk of STIs. An increased risk of HIV was reported to be associated with a history of sexual abuse and violence. The implications of the study findings in relation to methodological issues, clinical significance, and future research direction are discussed.
AT2 Receptor-Interacting Proteins ATIPs in the Brain
Authors: Rodrigues-Ferreira Sylvie , le Rouzic Erwann , Pawlowski Traci , Srivastava Anand , Margottin-Goguet Florence , Nahmias Clara
Published: January 2013

A complete renin-angiotensin system (RAS) is locally expressed in the brain and fulfills important functions. Angiotensin II, the major biologically active peptide of the RAS, acts via binding to two main receptor subtypes designated AT1 and AT2. The present paper focuses on AT2 receptors, which have been reported to have neuroprotective effects on stroke, degenerative diseases, and cognitive functions. Our group has identified a family of AT2 receptor interacting proteins (ATIPs) comprising three major members (ATIP1, ATIP3, and ATIP4) with different intracellular localization. Of interest, all ATIP members are expressed in brain tissues and carry a conserved domain able to interact with the AT2 receptor intracellular tail, suggesting a role in AT2-mediated brain functions. We summarize here current knowledge on the ATIP family of proteins, and we present new experimental evidence showing interaction defects between ATIP1 and two mutant forms of the AT2 receptor identified in cases of mental retardation. These studies point to a functional role of the AT2/ATIP1 axis in cognition.
Contribution of OATP1B1 and OATP1B3 to the Disposition of Sorafenib and Sorafenib-Glucuronide
Authors: Zimmerman Eric I. , Hu Shuiying , Roberts Justin L. , Gibson Alice A. , Orwick Shelley J. , Li Lie , Sparreboom Alex , Baker Sharyn D.
Published: January 2013

Purpose: Many tyrosine kinase inhibitors (TKI) undergo extensive hepatic metabolism, but mechanisms of their hepatocellular uptake remain poorly understood. We hypothesized that liver uptake of TKIs is mediated by the solute carriers OATP1B1 and OATP1B3.

Experimental Design: Transport of crizotinib, dasatinib, gefitinib, imatinib, nilotinib, pazopanib, sorafenib, sunitinib, vandetanib, and vemurafenib was studied in vitro using artificial membranes (PAMPA) and HEK293 cell lines stably transfected with OATP1B1, OATP1B3, or the ortholog mouse transporter, Oatp1b2. Pharmacokinetic studies were conducted with Oatp1b2-knockout mice and humanized OATP1B1- or OATP1B3-transgenic mice.

Results: All 10 TKIs were identified as substrates of OATP1B1, OATP1B3, or both. Transport of sorafenib was investigated further, as its diffusion was particularly low in the PAMPA assay (<4%) than other TKIs that were transported by both OATP1B1 and OATP1B3. Whereas Oatp1b2 deficiency in vivo had minimal influence on parent and active metabolite N-oxide drug exposure, plasma levels of the glucuronic acid metabolite of sorafenib (sorafenib-glucuronide) were increased more than 8-fold in Oatp1b2-knockout mice. This finding was unrelated to possible changes in intrinsic metabolic capacity for sorafenib-glucuronide formation in hepatic or intestinal microsomes ex vivo. Ensuing experiments revealed that sorafenib-glucuronide was itself a transported substrate of Oatp1b2 (17.5-fold vs. control), OATP1B1 (10.6-fold), and OATP1B3 (6.4-fold), and introduction of the human transporters in Oatp1b2-knockout mice provided partial restoration of function.

Conclusions: These findings signify a unique role for OATP1B1 and OATP1B3 in the elimination of sorafenib-glucuronide and suggest a role for these transporters in the in vivo handling of glucuronic acid conjugates of drugs. Clin Cancer Res; 19(6); 1458–66. ©2013 AACR.
Mild Improvement in Symptoms and Pulmonary Function in a Long-Term Follow-Up of Patients with Toluene Diisocyanate-Induced Asthma
Authors: Talini D. , Novelli F. , Bacci E. , Costa F. , Dente F.L. , Di Franco A. , Malagrinò L. , Vagaggini B. , Paggiaro P.
Published: January 2013

Background: Long-term follow-up of diisocyanate-induced occupational asthma has been occasionally reported. Methods: We studied the outcome of toluene diisocyanate (TDI)-induced asthma in 46 patients at diagnosis and after a follow-up of 11 ± 3.6 years. Symptoms, anti-asthma therapy, forced expiratory volume in 1 s (FEV1) and bronchial hyperresponsiveness to methacholine were assessed. Results: A significant improvement in FEV1 (% predicted) and PD20FEV1 methacholine was observed at follow-up in comparison with diagnosis. Anti-asthma treatment was performed by 42% of patients at diagnosis and by 70% at follow-up. At the time of follow-up, 32 subjects had been removed from exposure for 6.0 ± 6.9 years, whereas 14 subjects continued to work with reduced exposure to TDI. There was a significant reduction in the prevalence of attacks of shortness of breath and dyspnoea at follow-up, but only in unexposed patients. PD20FEV1 was significantly improved only in patients with a lower FEV1 at diagnosis and in those who have ceased work. Logistic regression analysis, using different models with some independent variables, showed that there were no significant determinants of improvement in FEV1 at follow-up, while a shorter duration of symptoms before diagnosis was a significant predictor of improvement in PD20FEV1 at follow-up. Conclusions: Asthma-like symptoms, bronchial hyperresponsiveness and airway obstruction improved, but did not normalize, after a long-term follow-up with cessation or reduction in TDI exposure, mainly in subjects with an early diagnosis of occupational asthma and in patients with a lower baseline FEV1 no longer exposed to TDI.
Bed Bug Saliva Causes Release of Monocytic Inflammatory Mediators: Plausible Cause of Cutaneous Bite Reactions
Authors: Goddard Jerome , Hasenkampf Nicole , Edwards Kristine T. , de Shazo Richard , Embers Monica E.
Published: January 2013

Bed bugs may cause mild to severe cutaneous reactions. We studied the ability of bed bug salivary extract (SGE) to induce inflammatory reactions responsible for cutaneous manifestations and found that SGE stimulated the production of several potent chemokines and cytokines from macrophages. Chemokines induced by SGE included those known to recruit eosinophils (eotaxin), attract neutrophils [interleukin (IL)-8] or induce their survival and proliferation (granulocyte colony-stimulating factor). Cytokines involved in cell-mediated immunity, including IL-7, IL-10 and IL-12, were also induced. Saliva of bed bugs contains protein and non-protein molecules that have pleotropic effects on macrophages, orchestrating the immune response in the skin after bed bug bites.
Refinement of Swedish Administrative Registers to Monitor Stroke Events on the National Level
Authors: Köster Max , Asplund Kjell , Johansson Åsa , Stegmayr Birgitta
Published: January 2013

Background: Routinely collected databases are kept for administrative purposes. We have refined the analyses of the Swedish National Patient Register and the Cause of Death Register and explored their validity to monitor stroke at the population level. Methods: First-ever strokes (incident cases) and all stroke events were measured by combining the two administrative registers and adding refinements. The administrative registers were validated against the Northern Sweden MONICA, a well-validated population-based epidemiological stroke register. Positive predictive values (PPVs) and sensitivity were calculated. Results: After refinements (restriction to first-ever strokes and additional minor delineations), the PPV of the two administrative registers combined was 94% and sensitivity 92% when compared with all MONICA stroke categories together. For stroke attacks (first and recurrent events together), the PPV in the administrative registers was 85% and sensitivity 91%. The PPV was higher in women than in men, whereas the sensitivity was similar. The PPV was lower but sensitivity higher in people below compared with those above 75 years of age. Both PPV and sensitivity were lower among fatal cases than among cases that survived 28 days. Conclusions: After refinement, Swedish national administrative registers may, with some caveats, be used as a low-resource-consuming alternative to crudely monitor stroke incidence rates at the national level. If further accuracy is strived for, high-quality conventional epidemiological registers are required.
Longitudinal Measurements of Oxygen Consumption in Growing Infants during the First Weeks after Birth: Old Data Revisited
Authors: Sinclair J.C. , Thorlund K. , Walter S.D.
Published: January 2013

Background: In a study conducted in 1966–1969, longitudinal measurements were made of the metabolic rate in growing infants. Statistical methods for analyzing longitudinal data weren’t readily accessible at that time. Objectives: To measure minimal rates of oxygen consumption (V·O2, ml/min) in growing infants during the first postnatal weeks and to determine the relationships between postnatal increases in V·O2, body size and postnatal age. Methods: We studied 61 infants of any birth weight or gestational age, including 19 of very low birth weight. The infants, nursed in incubators, were clinically well and without need of oxygen supplementation or respiratory assistance. Serial measures of V·O2 using a closed-circuit method were obtained at approximately weekly intervals. V·O2 was measured under thermoneutral conditions with the infant asleep or resting quietly. Data were analyzed using mixed-effects models. Results: During early postnatal growth, V·O2 rises as surface area (m2)1.94 (standard error, SE 0.054) or body weight (kg)1.24 (SE 0.033). Multivariate analyses show statistically significant effects of both size and age. Reference intervals (RIs) for V·O2 for fixed values of body weight and postnatal age are presented. As V·O2 rises with increasing size and age, there is an increase in the skin-operative environmental temperature gradient (T skin-op) required for heat loss. Required T skin-op can be predicted from surface area and heat loss (heat production minus heat storage). Conclusions: Generation of RIs for minimal rates of V·O2 in growing infants from the 1960s was enabled by application of mixed-effects statistical models for analyses of longitudinal data. Results apply to the precaffeine era of neonatal care.
Involvement of the Nitric Oxide/Cyclic Guanylate Monophosphate Pathway in the Pilocarpine-Induced Seizure Model in Mice
Authors: Vasconcelos Rios Emiliano Ricardo , Moura Rocha Nayrton Flávio , Rodrigues Carvalho Alyne Mara , Freire Vasconcelos Leonardo , Leite Dias Marília , de Carvalho Lima Camila Nayane , Soares Lopes Kamila , Cavalcante Melo Francisca Helvira , de França Fonteles Marta Maria
Published: January 2013

The present study was designed to investigate the involvement of the nitric oxide (NO)/cyclic guanylate monophosphate pathway in pilocarpine-induced seizures in mice. Male Swiss mice (26–32 g) were used as the in vivo model. The following pharmacological tools were utilized: the non-selective NO synthase (NOS) inhibitor L-NAME (10 mg/kg, i.p.), a preferential inducible NOS (iNOS) inhibitor aminoguanidine (25 mg/kg, i.p.), a highly specific iNOS inhibitor 1400W (2.5 mg/kg, i.p.), the NO donor L-arginine (150 mg/kg, i.p.), and the soluble guanylyl cyclase inhibitor ODQ (10 mg/kg, i.p.). The animals were divided into groups (n = 8) and pretreated for 30 min before receiving pilocarpine (400 mg/kg, i.p.), while the control group received only pilocarpine. They were observed for 60 min to measure initial seizure latency, latency till death, and mortality. An administration of L-NAME or ODQ delayed the onset of initial seizure, increased latency till death, and produced a 25% survival rate. Aminoguanidine increased the initial seizure and latency until death, and administration of 1400W did not have an effect. Incremental increases of NO by L-arginine were capable of decreasing the seizure and death latency. These results support the idea that the constitutive NOS, probably neuronal NOS, followed by soluble guanylyl cyclase activation is involved in the convulsive responses caused by pilocarpine administration.
Antitumor Effect of Everolimus in Preclinical Models of High-Grade Gastroenteropancreatic Neuroendocrine Carcinomas
Authors: Bollard Julien , Couderc Christophe , Blanc Martine , Poncet Gilles , Lepinasse Florian , Hervieu Valérie , Gouysse Géraldine , Ferraro-Peyret Carole , Benslama Noura , Walter Thomas , Scoazec Jean-Yves , Roche Colette
Published: January 2013

Background/Aims: While the range of therapeutic options for well-differentiated gastroenteropancreatic neuroendocrine tumors has recently increased with the emergence of targeted therapies, such as mTOR inhibitors, there is no recent progress in the treatment of poorly differentiated neuroendocrine carcinomas (PDNECs). Since PDNECs have been shown to strongly express mTOR pathway components, the aim of the present study was to assess the antitumor effect of the mTOR inhibitor everolimus in preclinical models of PDNECs. Methods: The expression of mTOR pathway components and their response to everolimus were assessed in two neuroendocrine cell lines: STC-1 and GluTag. A xenograft model of intrahepatic dissemination in the nude mouse, based on the intrasplenic injection of either STC-1 and GluTag tumor cells, was used. Animals were started on everolimus treatment 3 days after injection. The effects of treatment on tumor growth, proliferative capacities, apoptosis and in situ expression of mTOR pathway components were assessed. Results: The expression of mTOR pathway components was comparable in STC-1 and GluTag cells and in human PDNECs and could be inhibited in vitro by everolimus. In vivo, the tumor volume of STC-1 and GluTag xenografts was significantly reduced in treated animals (6.05 ± 1.84% as compared to 21.76 ± 3.88% in controls). Everolimus treatment also induced a significant decrease in Ki67 index and in the phosphorylation levels of the two major effectors of mTOR, p70S6K and 4E-BP1. Conclusion: Our experimental data suggest that mTOR inhibition could be considered a therapeutic option for high-grade gastroenteropancreatic neuroendocrine tumors.
Induction of Cooling With a Passive Head and Neck Cooling Device
Authors: Poli Sven , Purrucker Jan , Priglinger Miriam , Diedler Jennifer , Sykora Marek , Popp Erik , Steiner Thorsten , Veltkamp Roland , Bösel Julian , Rupp André , Hacke Werner , Hametner Christian
Published: January 2013

Background and Purpose—

Therapeutic hypothermia improves clinical outcome after cardiac arrest and appears beneficial in other cerebrovascular diseases. We conducted this study to investigate the relationship between surface head/neck cooling and brain temperature.

Methods—

Prospective observational study enrolling consecutive patients with severe ischemic or hemorrhagic stroke undergoing intracranial pressure (ICP) and brain temperature monitoring. Arterial pressure, ICP, cerebral perfusion pressure, heart rate, brain, tympanic, and bladder temperature were continuously registered. Fifty-one applications of the Sovika cooling device were analyzed in 11 individual patients.

Results—

Sovika application led to a significant decrease of brain temperature compared with baseline with a maximum of −0.36°C (SD, 0.22) after 49 minutes (SD, 17). During cooling, dynamics of brain temperature differed significantly from bladder (−0.25°C [SD, 0.15] after 48 minutes [SD, 19]) and tympanic temperature (−1.79°C [SD, 1.19] after 37 minutes [SD, 16]). Treatment led to an increase in systolic arterial pressure by >20 mm Hg in 14 applications (n=7 patients) resulting in severe hypertension (>180 mm Hg) in 4 applications (n=3). ICP increased by >10 mm Hg in 7 applications (n=3), led to ICP crisis >20 mm Hg in 6 applications (n=3), and a drop of cerebral perfusion pressure <50 mm Hg in 1 application.

Conclusions—

Although the decrease of brain temperature after Sovika cooling device application was statistically significant, we doubt clinical relevance of this rather limited effect (−0.36°C). Moreover, the transient increases of blood pressure and ICP warrant caution.
Hemostatic Therapy in Experimental Intracerebral Hemorrhage Associated With Rivaroxaban
Authors: Zhou Wei , Zorn Markus , Nawroth Peter , Bütehorn Ulf , Perzborn Elisabeth , Heitmeier Stefan , Veltkamp Roland
Published: January 2013

Background and Purpose—

Rivaroxaban has recently been approved for stroke prevention in atrial fibrillation. However, lack of an effective antidote represents a major concern in the event of intracerebral hemorrhage (ICH). The aims of the present study were to establish a murine model of ICH associated with rivaroxaban, and to examine the effectiveness of different hemostatic factors in preventing excess hematoma expansion.

Methods—

In C57BL/6 mice receiving 10 or 30 mg/kg rivaroxaban by gastric gavage, plasma concentration, prothrombin time, and coagulation factor activities were measured repeatedly. Thirty minutes after inducing ICH by intrastriatal collagenase-injection, mice received an intravenous injection of either saline, prothrombin complex concentrate (100 U/kg), murine fresh frozen plasma (200 μL), or recombinant human Factor VIIa (1 mg/kg). ICH volume was quantified on brain cryosections and using hemoglobin spectrophotometry 24 hours later.

Results—

Rivaroxaban in 30 mg/kg dose substantially increased the hematoma volume in ICH induced by 0.060 U collagenase. Prothrombin complex concentrate, fresh frozen plasma, or Factor VIIa prevented excess hematoma expansion caused by anticoagulation. Prevention of hematoma expansion by prothrombin complex concentrate was dose-dependent. None of the 3 agents completely corrected the prolonged prothrombin time, although they restored the activities of deficient FII and X.

Conclusions—

Prothrombin complex concentrate, Factor VIIa, and fresh frozen plasma prevent excess intracerebral hematoma expansion in a murine ICH model associated with rivaroxaban. The efficacy and safety of this reversal strategy must be further evaluated in clinical studies.
Convergent Validity and Interrater Reliability of Estimating the ABCD
2
Score From Medical Records
Authors: Ishida Koto , Raser-Schramm Jonathan M. , Wilson Christina A. , Kasner Scott E. , Mullen Michael T. , Messe Steven R. , Cucchiara Brett
Published: January 2013

Background and Purpose—

The ABCD
2
score is increasingly used for risk stratification of transient ischemic attack patients. We sought to determine the reliability and convergent validity of retrospective ABCD
2
score estimation from medical records.

Methods—

We compared ABCD
2
scores that were prospectively determined by a vascular neurology attending to scores determined retrospectively from medical record review. Emergency department records and neurology consult notes for patients with acute transient ischemic attack were abstracted with explicit ABCD
2
scoring redacted. Scores were estimated by 2 independent raters using these records. Estimated ABCD
2
component scores, total scores, and risk category were compared both between retrospective raters and with prospectively obtained scores. Reliability was assessed using unweighted κ statistics.

Results—

Interrater reliability was substantial with 72% exact agreement in total score between retrospective raters (κ=0.64) and nearly perfect with 82% agreement for ABCD
2
category (κ=0.71). Interrater agreement was best for age and diabetes mellitus and poorest for clinical features and duration. Agreement between the retrospective raters and prospectively obtained score was >90% for age, blood pressure, and diabetes mellitus, but only ≈70% for clinical features and duration. Retrospectively, estimated total ABCD
2
score exactly matched the prospective score in 58% of patients for rater 1 and 44% of patients for rater 2. Retrospectively, estimated ABCD
2
category matched the prospectively scored category in 67% of patients for rater 1 and 71% of patients for rater 2.

Conclusions—

The ABCD
2
score can be abstracted from medical records with substantial interrater reliability but limited convergent validity. This may lead to misclassification of risk category in more than one third of patients.
Increase of clutch size triggers clutch destruction behaviour in common moorhens (Gallinula chloropus) during the incubation period
Authors: Wang Longwu , Yang Canchao , Hsu Yu-Cheng , Antonov Anton , Moksnes Arne , Røskaft Eivin , Liang Wei , Stokke Bård Gunnar
Published: January 2013

Conspecific brood parasitism (CBP) is common in a variety of animal taxa, including birds. In coots (Fulica spp.), and the closely related moorhens (Gallinula spp.), such parasitism is especially common, and hosts experience considerable costs through increased chick competition soon after hatching. Hence, these birds have evolved egg recognition and rejection abilities, e.g., egg counting, burying the foreign eggs, assigning them suboptimal positions within the mixed clutch, or deserting parasitized clutches. For common moorhens (Gallinula chloropus) it has been shown that desertion of parasitized nests pays most at the early egg laying stage. Later on, the costs of desertion exceed the costs of brood parasitism and acceptance is favoured. Here we tested moorhen egg discrimination behaviour during the incubation stage when acceptance of foreign eggs is expected. Four treatments were applied: (1) single added non-mimetic pale blue egg, (2) single added non-mimetic white chicken egg, (3) four foreign conspecific eggs added to the clutch and (4) four foreign conspecific eggs exchanged for four host eggs. Moorhens responded by egg destruction (47%) only to the increased clutch size but not to foreign egg colour and size match. In three nests where egg destruction occurred, all the eggs in the mixed clutch were destroyed by pecking, in two other nests one of the foreign eggs were pecked, while two other nests were deserted. These results are puzzling since moorhens have been shown to possess refined egg recognition abilities. To our knowledge, such destruction of parasitized clutches by moorhens during incubation has not previously been reported. We suggest that after clutch completion, moorhens use increase in clutch size as a cue to determine if they have been parasitized, and some individuals choose to reject parasitic eggs by deserting or destroying the whole clutch.
Global Capitalism and “North-South” Unevenness: In Light of Ranking, Statistical Correlations, and Profits from the Forbes’ Worldwide List of 2000 Top Firms
Authors: del Castillo-Mussot Marcelo , Sprague Jeb , Garcia Alfredo de la Lama
Published: January 2013

Abstract

While a ‘north-south divide’ in world capitalism has been pointed to for many years, in this article we examine how this unevenness continues in today’s epoch of capitalist globalization. To examine this phenomenon, we analyze a recentForbes Magazineannual ranking of the leading 2000 companies in the world (G2000), by grouping or ‘boxing’ these companies by their 62 domiciles to calculate aggregated sales, profits, assets and market value and correlating these quantities with the GDP of the corresponding domicile. This is an approximation to reality, since the variety of transnational capital and associated global processes make it nowadays problematic to assign national labels to capital. Regardless of where the whole business circuit takes place, we found thatthe GDP of each country is directly proportional, more or less, to the economic strength of all G2000 top firms based or registered in that country. These proportionalities tend to hover around a certain level globally, yet the correlation is lower for the ‘global south’ (as some describe it). We can also identify important regional variations of ratios such as profits/sales. Other ratios could also be easily calculated from our results. Together these findings help lead to a more nuanced understanding of transnational corporations (TNCs), but also suggest more basically, for instance, that the ‘global north’ remains to some degree more penetrated by TNCs (of the G2000).
Adorno, Auschwitz, and the New Categorical Imperative
Authors: Ostrove Geoff
Published: January 2013

Abstract

Theodor Adorno (2001) once claimed, “Hitler has imposed a new categorical imperative upon humanity in the state of their unfreedom: to arrange their thinking and conduct, so that Auschwitz never repeats itself, so that nothing similar ever happen again” (p. 358). In this article I analyze exactly what Adorno meant by this statement, and how he believes humanity should act in order to arrange their thinking, conduct, and communication so that nothing similar to the Holocaust can ever happen again. I will also explore Adorno’s thoughts on why the Holocaust was able to occur, how contemporary society should respond to such a catastrophe, and why he felt the creation of the modern state of Israel was not an appropriate response to the Holocaust. Adorno felt that the only true form of revolutionary praxis was to change the dominant means of production and any lesser form of rebellion was futile and only reified the contemporary commodity-form capitalist system.
Reviewing a Decade of Research on the “Base/Bottom of the Pyramid” (BOP) Concept
Authors: Kolk Ans , Rivera-Santos Miguel , Rufín Carlos
Published: January 2013

In 1998-1999, Prahalad and colleagues introduced the base/bottom of the pyramid (BOP) concept in an article and a working paper. This article’s goal is to answer the following question: What has become of the concept over the decade following its first systematic exposition in 1999? To answer this question, the authors conducted a systematic review of articles on the BOP, identifying 104 articles published in journals or proceedings over a 10-year period (2000-2009). This count excludes books, chapters, and teaching cases. The review shows that the BOP concept evolved dramatically following Prahalad’s original call to multinational enterprises (MNEs). Deemphasizing the role of MNEs over time, published BOP articles portray a more complex picture, with wide variations in terms of BOP contexts, of BOP initiatives, and of impacts of the BOP approach. A simple framework for organizing the reviewed articles helps discuss findings, identify the gaps that still exist in the literature, and suggest directions for future research.
P2X7 Receptor and Cytokines Contribute to Extra-territorial Facial Pain
Authors: Murasaki K. , Watanabe M. , Takahashi K. , Ito G. , Suekawa Y. , Inubushi T. , Hirose N. , Uchida T. , Tanne K.
Published: January 2013

The whisker pad area (WP) is innervated by the second branch of the trigeminal nerve and experiences allodynia and hyperalgesia following transection of the mental nerve (MN; the third branch of the trigeminal nerve). However, the mechanisms of this extra-territorial pain remain unclear. The ionotropic P2X7 ATP receptor (P2X7) in microglia is known to potentiate, via cytokines, the perception of noxious stimuli, raising the possibility that P2X7 and cytokines are involved in this extra-territorial pain. One day after MN transection (MNT), WP allodynia/hyperalgesia developed, which lasted for > 8 wks. Activation of microglia and up-regulation of P2X7, membrane-bound tumor necrosis factor (TNF)-α (mTNF-α), and soluble TNF-α (sTNF-α) in the trigeminal sensory nuclear complex (TNC) were evident for up to 6 wks after MNT. Allodynia/hyperalgesia after MNT was blocked by intracisternal administration of etanercept, a recombinant TNF-α receptor (p75)-Fc fusion protein. Intracisternal A438079, a P2X7 antagonist, also attenuated allodynia/hyperalgesia and blocked up-regulation of mTNF-α and sTNF-α in the TNC. We conclude that sTNF-α released by microglia following P2X7 activation may be important in both the initiation and maintenance of extra-territorial pain after MNT.
How a “New Legal History” Might Be Possible
Authors: You Chenjun
Published: January 2013

The study of Chinese legal history has undergone a tremendous change in the United States since the 1990s. Antiquated views and biased opinions of past decades have been rethought and criticized to a considerable extent. At the cutting edge of this new academic trend is the UCLA research group of Chinese legal history. Their scholarship as a whole exemplifies the features of what this article calls a “new Chinese legal history”—namely, conjoining the empirical (the extensive use of judicial archives in China) with the theoretical (drawing upon and dialoguing with well-established theories in social sciences), with the intention of formulating new and illuminating middle-level concepts. Moreover, their keen “historical sense” helps us understand the historical roots of contemporary problems, thus overcoming the epistemological problem of Chinese legal history studies often being regarded as useless.
Ambivalent Representations of Muslims in Medieval Indian Theatre
Authors: Leclère Basile
Published: January 2013

From the eleventh century AD onwards, some Indian dramatists began to derive the plot of their plays from contemporary events, such as the military achievements of their patron, despite the prohibition of this kind of subjects by theoreticians. As the neighbouring Afghan and Turkish rulers of Ghazna and Ghūr were threatening India then, Muslim characters made their appearance in some of these historical plays, like Somadeva’s Lalitavigraharāja ( c. AD 1153) and Jayasiṃhasūri’s Hammīramadamardana ( c. AD 1227–30). Consequently, these texts constitute a counterpoint to the Persian chronicles and give us the unique opportunity of ascertaining how Muslim invaders were perceived by Indian people during the political upheavals of the twelfth and thirteenth centuries ad. The article first analyzes how Muslim characters are reviled and even demonized by means of specific dramatic languages as well as other literary devices, and then demonstrates that Muslim people were far from being the only target of this process of demonization: according to the circumstances, it was also used by devotees of Viṣṇu against Jains, Jains against followers of Śiva and even between rival sects of one and a same religion. Furthermore the plays betray a genuine acquaintance of their authors with the realities of the Islamic world. Though portraying Muslim characters in a more virulent way than Somadeva, Jayasiṃhasūri transposed foreign names into Sanskrit rather carefully and gave a faithful account of the political, military and cultural particularities of Muslim people.
Psychological adaptation to visual impairment: The traditional grief process revised
Authors: Bergeron Catherine M , Wanet-Defalque Marie-Chantal
Published: January 2013

The objective of this study was to explore the pattern of adaptation in patients who have been diagnosed with visual impairment. Participants ( N = 700), recruited in the Montreal area (Canada), underwent a structured interview in order to collect information on the duration of the acquired visual impairment and answered the ‘Brief Cope’, ‘Satisfaction with Life Scale’ and ‘Center for Epidemiologic Studies–Depression Scale’ (CES-D). Multivariate analysis of covariance (MANCOVA) revealed that patients who have lived with vision impairment for over 2 years reach significantly higher acceptance and lower denial levels compared to those of patients who had recent vision loss (≤2 years). We also found that acceptance was positively correlated with well-being and denial with depression, while acceptance was negatively correlated with depression and, likewise, denial with well-being. Our study results suggest that patients who have been diagnosed with visual impairment engage in an adaptative coping style early in the grief process.