bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting clinical outcome in feline oral squamous cell carcinoma: tumour initiating cells, telomeres and telomerase
Authors: Yoshikawa H. , Maranon D. G. , Battaglia C. L. R. , Ehrhart E. J. , Charles J. B. , Bailey S. M. , LaRue S. M.
Published: September 2014

Feline oral squamous cell carcinoma (SCC) has very poor prognosis. Here, a retrospective pilot study was conducted on 20 feline oral SCC patients who underwent stereotactic radiation therapy (SRT), to evaluate: (1) the value of putative tumour initiating cell (TIC) markers of human head and neck SCC (CD44, Bmi‐1); (2) telomere length (TL) specifically in putative TICs; and (3) tumour relative telomerase activity (TA). Significant inverse correlations were found between treatment outcomes and Bmi‐1 expression, supporting the predictive value of Bmi‐1 as a negative prognostic indicator. While TL exhibited a wide range of variability, particularly in very short fractions, many tumours possessed high levels of TA, which correlated with high levels of Bmi‐1, Ki67 and EGFR. Taken together, our results imply that Bmi‐1 and telomerase may represent novel therapeutic targets in feline oral SCC, as their inhibition – in combination with SRT – would be expected to have beneficial treatment outcome.
The Presence of Borrelia miyamotoi, A Relapsing Fever Spirochaete, in Questing Ixodes ricinus in Belgium and in The Netherlands
Authors: Cochez C. , Heyman P. , Heylen D. , Fonville M. , Hengeveld P. , Takken W. , Simons L. , Sprong H.
Published: September 2014

Borrelia miyamotoi is a tick‐borne bacterium that may cause relapsing fever in humans. As this pathogen has been discovered in Europe only recently, only little is known about its local impact on human health and its spatial distribution. In this study, we show the results of PCR screenings for B. miyamotoi in flagged Ixodes ricinus from Belgium and the Netherlands. B. miyamotoi was detected in nine of thirteen, and three of five locations from the Netherlands and Belgium, respectively. These outcomes indicate that B. miyamotoi is more spread than previously thought. The mean infection rate B. miyamotoi was 1.14% for Belgium and 3.84% for the Netherlands.
Single unit hyperactivity and bursting in the auditory thalamus of awake rats directly correlates with behavioural evidence of tinnitus
Authors: Kalappa Bopanna I. , Brozoski Thomas J. , Turner Jeremy G. , Caspary Donald M.
Published: September 2014

Key points

Medial geniculate body (MGB) single units recorded from sound‐exposed animals with behavioural evidence of tinnitus exhibits enhanced spontaneous firing and burst properties.

MGB units in tinnitus animals exhibit increased rate‐level function slope when driven by broadband noise and tones at the unit's characteristic frequency.

Elevated patterns of neuronal activity and altered bursting showed a significant positive correlation with animals’ tinnitus scores.

Tinnitus is an auditory percept without an environmental acoustic correlate. Contemporary tinnitus models hypothesize tinnitus to be a consequence of maladaptive plasticity‐induced disturbance of excitation–inhibition homeostasis, possibly convergent on medial geniculate body (MGB, auditory thalamus) and related neuronal networks. The MGB is an obligate acoustic relay in a unique position to gate auditory signals to higher‐order auditory and limbic centres. Tinnitus‐related maladaptive plastic changes of MGB‐related neuronal networks may affect the gating function of MGB and enhance gain in central auditory and non‐auditory neuronal networks, resulting in tinnitus. The present study examined the discharge properties of MGB neurons in the sound‐exposure gap inhibition animal model of tinnitus. MGB single unit responses were obtained from awake unexposed controls and sound‐exposed adult rats with behavioural evidence of tinnitus. MGB units in animals with tinnitus exhibited enhanced spontaneous firing, altered burst properties and increased rate‐level function slope when driven by broadband noise and tones at the unit's characteristic frequency. Elevated patterns of neuronal activity and altered bursting showed a significant positive correlation with animals’ tinnitus scores. Altered activity of MGB neurons revealed additional features of auditory system plasticity associated with tinnitus, which may provide a testable assay for future therapeutic and diagnostic development.
Tribological Improvements of Dispersed Nanodiamond Additives in Lubricating Mineral Oil
Authors: Marko Matthew , Kyle Jonathan , Branson Blake , Terrell Elon
Published: September 2014

An effort was conducted to study and characterize the effects of nanodiamond particles as an additive to lubricating mineral oil. The tests were run for varying concentrations ranging from pure mineral oil to 0.01% weight-concentration of nanodiamonds. The friction was measured throughout the tests, and the resulting wear was measured with optical profilometry. It was observed that both the average friction coefficient and the wear would decrease proportionally to the concentration of nanodiamond particles, and the 0.01% nanodiamond weight concentration was observed to improve the tribological performance of lubricating mineral oil. Chemical analysis of contacting surfaces showed no significant distinction from the nanodiamond mixture versus the pure mineral oil, while particle size analysis demonstrated that the nanoparticles themselves remained intact (i.e., no breakup) in the contact interface. This helps to conclude that a mechanical and not a chemical effect of the nanodiamond particles helped to protect the metallic surface from wear and improve the lubricating ability of the mineral oil.
Rotating Stall Observations in a High Speed Compressor—Part II: Numerical Study
Authors: Dodds J. , Vahdati M.
Published: September 2014

In this two-part paper the phenomenon of part span rotating stall is studied. The objective is to improve understanding of the physics by which stable and persistent rotating stall occurs within high speed axial flow compressors. This phenomenon is studied both experimentally (Part I) and numerically (Part II). The experimental observations reported in Part I are now explored through the use of 3D unsteady Reynolds-averaged Navier–Stokes (RANS) simulation. The objective is to both validate the computational model and, where possible, explore some physical aspects of the phenomena. Unsteady simulations are presented, performed at a fixed speed with the three rows of variable stator vanes adjusted to deliberately mismatch the front stages and provoke stall. Two families of rotating stall are identified by the model, consistent with experimental observations from Part I. The first family of rotating stall originates from hub corner separations developing on the stage 1 stator vanes. These gradually coalesce into a multicell rotating stall pattern confined to the hub region of the stator and its downstream rotor. The second family originates from regions of blockage associated with tip clearance flow over the stage 1 rotor blade. These also coalesce into a multicell rotating stall pattern of shorter length scale confined to the leading edge tip region. Some features of each of these two patterns are then explored as the variable stator vanes (VSVs) are mismatched further, pushing each region deeper into stall. The numerical predictions show a credible match with the experimental findings of Part I. This suggests that a RANS modeling approach is sufficient to capture some important aspects of part span rotating stall behavior.
Failure Prediction of Curved Wide Plates Using the Strain-Based Failure Assessment Diagram With Correction for Constraint and Notch Radius
Authors: Horn Anthony , Trull Mikhail , Hertelé Stijn
Published: September 2014

The strain-based failure assessment diagram (SB-FAD) has been developed for predicting failure from flaws in components subjected to high plastic strains. In this paper, a combined numerical and experimental approach is used to apply the SB-FAD to predict failure from a series of API 5L grades X80 and X100 curved wide plate (CWP) specimens with shallow notches machined into the pipe girth weld. For the CWP specimens tested in this work, the SB-FAD in its unmodified form resulted in over-conservative predictions of failure. This is attributed to the SB-FAD assuming high constraint conditions and the presence of a sharp fatigue crack, whereas the CWP specimens tested in this work were low constraint and contained a shallow machined notch without fatigue cracks. A modification of the SB-FAD is then proposed to account for nonsharp defects loaded to high plastic strains under conditions of low constraint. The resulting predictions of the modified SB-FAD show significantly reduced conservatism compared to the unmodified SB-FAD.
Acoustic characteristics of the clothes used for a wearable recording device
Authors: VanDam Mark
Published: September 2014

There has been increasing attention in the literature to wearable acoustic recording devices, particularly to examine naturalistic speech in disordered and child populations. Recordings are typically analyzed using automatic procedures that critically depend on the reliability of the collected signal. This work describes the acoustic amplitude response characteristics and the possibility of acoustic transmission loss using several shirts designed for wearable recorders. No difference was observed between the response characteristics of different shirt types or between shirts and the bare-microphone condition. Results are relevant for research, clinical, educational, and home applications in both practical and theoretical terms.
A fractional K-BKZ constitutive formulation for describing the nonlinear rheology of multiscale complex fluids
Authors: Jaishankar Aditya , McKinley Gareth H.
Published: September 2014

The relaxation processes of a wide variety of soft materials frequently contain one or more broad regions of power-law like or stretched exponential relaxation in time and frequency. Fractional constitutive equations have been shown to be excellent models for capturing the linear viscoelastic behavior of such materials, and their relaxation modulus can be quantitatively described very generally in terms of a Mittag–Leffler function. However, these fractional constitutive models cannot describe the nonlinear behavior of such power-law materials. We use the example of Xanthan gum to show how predictions of nonlinear viscometric properties, such as shear-thinning in the viscosity and in the first normal stress coefficient, can be quantitatively described in terms a nonlinear fractional constitutive model. We adopt an integral K-BKZ framework and suitably modify it for power-law materials exhibiting Mittag–Leffler type relaxation dynamics at small strains. Only one additional parameter is needed to predict nonlinear rheology, which is introduced through an experimentally measured damping function. Empirical rules such as the Cox–Merz rule and Gleissle mirror relations are frequently used to estimate the nonlinear response of complex fluids from linear rheological data. We use the fractional model framework to assess the performance of such heuristic rules and quantify the systematic offsets, or shift factors, that can be observed between experimental data and the predicted nonlinear response. We also demonstrate how an appropriate choice of fractional constitutive model and damping function results in a nonlinear viscoelastic constitutive model that predicts a flow curve identical to the elastic Herschel-Bulkley model. This new constitutive equation satisfies the Rutgers-Delaware rule, which is appropriate for yielding materials. This K-BKZ framework can be used to generate canonical three-element mechanical models that provide nonlinear viscoelastic generalizations of other empirical inelastic models such as the Cross model. In addition to describing nonlinear viscometric responses, we are also able to provide accurate expressions for the linear viscoelastic behavior of complex materials that exhibit strongly shear-thinning Cross-type or Carreau-type flow curves. The findings in this work provide a coherent and quantitative way of translating between the linear and nonlinear rheology of multiscale materials, using a constitutive modeling approach that involves only a few material parameters.
Detecting topological currents in graphene superlattices
Authors: Gorbachev R. V. , Song J. C. W. , Yu G. L. , Kretinin A. V. , Withers F. , Cao Y. , Mishchenko A. , Grigorieva I. V. , Novoselov K. S. , Levitov L. S. , Geim A. K.
Published: September 2014

Making use of graphene's valleys

Graphene has two distinct valleys in its electronic structure, in which the electrons have the same energy. Theorists have predicted that creating an asymmetry between the two valleys will coax graphene into exhibiting the so-called valley Hall effect (VHE). In this effect, electrons from the two valleys move across the sample in opposite directions when the experimenters run current along the sample. Gorbachev
et al.
achieved this asymmetry by aligning graphene with an underlying layer of hexagonalboron nitride (hBN) (see the Perspective by Lundeberg and Folk). The authors measured the transport characteristics of the sample, which were consistent with the theoretical predictions for the VHE. The method may in the future lead to information processing using graphene's valleys.

Science
, this issue p.
448
; see also p.
422
Immune dysregulation in human subjects with heterozygous germline mutations in
CTLA4
Authors: Kuehn Hye Sun , Ouyang Weiming , Lo Bernice , Deenick Elissa K. , Niemela Julie E. , Avery Danielle T. , Schickel Jean-Nicolas , Tran Dat Q. , Stoddard Jennifer , Zhang Yu , Frucht David M. , Dumitriu Bogdan , Scheinberg Phillip , Folio Les R. , Frein Cathleen A. , Price Susan , Koh Christopher , Heller Theo , Seroogy Christine M. , Huttenlocher Anna , Rao V. Koneti , Su Helen C. , Kleiner David , Notarangelo Luigi D. , Rampertaap Yajesh , Olivier Kenneth N. , McElwee Joshua , Hughes Jason , Pittaluga Stefania , Oliveira Joao B. , Meffre Eric , Fleisher Thomas A. , Holland Steven M. , Lenardo Michael J. , Tangye Stuart G. , Uzel Gulbu
Published: September 2014

Beware of T cells that don't know how to stop

During an infection, T cells divide extensively and secrete proteins that can severely damage tissues. But T cells know when to stop—they express proteins on their surface such as CTLA4, which put on the brakes. Kuehn
et al.
now report genetic evidence of the importance of CTLA4 in humans (see the Perspective by Rieux-Laucat and Casanova). They identified six patients with mutations in one copy of
CTLA4
. Patients presented with symptoms of an overzealous immune response, with immune cells infiltrating their organs. The findings support the idea that CTLA4 tells the immune system when enough is enough.

Science
, this issue p.
1623
; see also p.
1560
Complete Genome Sequences of Two Escherichia coli O157:H7 Phages Effective in Limiting Contamination of Food Products
Authors: Hong Yingying , Pan Yanying , Harman Nicholas J. , Ebner Paul D.
Published: September 2014

We previously demonstrated that application of bacteriophages significantly reduced
Escherichia coli
O157:H7 contamination in spinach and ground beef. Here, we present the genomic sequences of two bacteriophages, vB_EcoS_FFH_1, a T5-like phage, and vB_EcoM_FFH_2, an rV5-like phage, used in those treatments.
Draft Genome Sequence of
Pseudoalteromonas
sp. Strain A2, an Isolate with High Antioxidative Activity from Arctic Seawater
Authors: Lin Xuezheng , Wang Zhen , Li Yang
Published: September 2014

Here we report the draft genome sequence of
Pseudoalteromonas
strain A2, isolated from Arctic seawater in the pack-ice zone, which has high antioxidative activity against H
2
O
2
. The genomics information of this strain will facilitate the study of antioxidative mechanisms, cold adaptation properties, and evolution of this genus.
De NovoWhole-Genome Sequence and Genome Annotation of Lichtheimia ramosa
Authors: Linde Jörg , Schwartze Volker , Binder Ulrike , Lass-Flörl Cornelia , Voigt Kerstin , Horn Fabian
Published: September 2014

We report the annotated draft genome sequence ofLichtheimia ramosa(JMRC FSU:6197). It has been reported to be a causative organism of mucormycosis, a rare but rapidly progressive infection in immunocompromised humans. The functionally annotated genomic sequence consists of 74 scaffolds with a total number of 11,510 genes.
Whole-Genome Sequencing of Streptomycin-Resistant Mycobacterium tuberculosis Isolate VRFCWCF MRTB 180 Reveals Novel and Potential Mutations for Resistance
Authors: Ramasubban Gayathri , Lakshmipathy Dhanurekha , Vetrivel Umashankar , Kulandai Lily Therese , Madhavan Hajib Narahari , Sridhar R. , Meenakshi N.
Published: September 2014

We announce the draft genome sequence of a streptomycin monoresistant
Mycobacterium tuberculosis
strain (VRFCWCF MRTB 180) isolated from sputum of a clinically suspected tuberculosis patient.
A 16-year-old boy with emphysematous gastritis and oesophageal candidiasis
Authors: Yusef Daniel , Waran Ariane , Vamvakiti Ekaterini
Published: September 2014

Emphysematous gastritis is a rare and frequently fatal condition caused by invasion of gas-forming bacteria into the gastric wall. There have only been a handful of reported cases in the paediatric population, and none of these have evidence of candidal infection or mucormycosis. Patients typically present with abdominal pain, vomiting, malaena and haematemesis. Risk factors for emphysematous gastritis are those that interfere with the natural barriers to infection in the stomach. Diagnosis is made on the basis of typical appearances on abdominal CT. Treatment is generally conservative with surgery reserved for failed medical management or later complications. Antimicrobial cover should be broad with a low threshold for antifungals. It is important to look for predisposing factors for this condition, perhaps including an assessment of the patient's immunocompetency. We present a 16-year-old boy with global developmental delay who presented with this condition associated with candidal infection.
Urethral defect with suspected corpus spongiosum herniation as a cause of stranguria and urethral haemorrhage in a dog
Authors: Newman Mark , Evans Natashia , Podadera Juan , Beijerink Niek , Voss Katja
Published: September 2014

A male neutered Staffordshire bull terrier presented for evaluation of urethral haemorrhage of three days duration. A urethral mass was identified on contrast radiography, ultrasonography and urethroscopy. An open excisional biopsy was performed and the mass appeared to arise from the vascular tissue beneath the urethral wall. Histopathology revealed evidence of ulceration and granulation; coupled with the clinical findings the mass appeared to be a herniation of corpus spongiosum through a defect in the urethral mucosa. Removal and closure of the urethral defect, along with postoperative propranolol, effected a clinical resolution. To the author's knowledge, a urethral mucosal defect as a cause of urethral haemorrhage has not been previously described in the dog.
Hematocrit dispersion in asymmetrically bifurcating vascular networks
Authors: Sriram Krishna , Intaglietta Marcos , Tartakovsky Daniel M.
Published: September 2014

Quantitative modeling of physiological processes in vasculatures requires an accurate representation of network topology, including vessel branching. We propose a new approach for reconstruction of vascular network, which determines how vessel bifurcations distribute red blood cells (RBC) in the microcirculation. Our method follows the foundational premise of Murray's law in postulating the existence of functional optimality of such networks. It accounts for the non-Newtonian behavior of blood by allowing the apparent blood viscosity to vary with discharge hematocrit and vessel radius. The optimality criterion adopted in our approach is the physiological cost of supplying oxygen to the tissue surrounding a blood vessel. Bifurcation asymmetry is expressed in terms of the amount of oxygen consumption associated with the respective tissue volumes being supplied by each daughter vessel. The vascular networks constructed with our approach capture a number of physiological characteristics observed in in vivo studies. These include the nonuniformity of wall shear stress in the microcirculation, the significant increase in pressure gradients in the terminal sections of the network, the nonuniformity of both the hematocrit partitioning at vessel bifurcations and hematocrit across the capillary bed, and the linear relationship between the RBC flux fraction and the blood flow fraction at bifurcations.
Urinary Prostaglandin E2 Metabolite and Breast Cancer Risk
Authors: Cui Yong , Shu Xiao-Ou , Gao Yu-Tang , Cai Qiuyin , Ji Bu-Tian , Li Hong-Lan , Rothman Nathaniel , Wu Jie , Yang Gong , Xiang Yong-Bing , Zheng Wei
Published: September 2014

Background: Levels of the cyclooxygenase 2 (COX2) enzyme are elevated in breast cancer tissue, and most COX2 effects are believed to be mediated through overproduction of prostaglandin E2 (PGE2). We evaluated associations between the primary urinary metabolite of PGE2 (PGE-M) and breast cancer risk.

Methods: A nested case–control study of 504 cases and 1,082 controls was conducted using data from the Shanghai Women's Health Study, a large population-based prospective cohort study of 74,941 Chinese women. Urinary PGE-M was measured using a liquid chromatography/tandem mass spectrometric method. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (95% CI) with adjustment for potential confounders.

Results: Overall, no association between urinary PGE-M and breast cancer was detected. However, a suggestive positive association was found among postmenopausal women. In particular, a clear dose–response relationship between urinary PGE-M and breast cancer was observed among postmenopausal women with a body mass index (BMI) < 25 kg/m2 (Plinear trend = 0.005). Among these women, risk of breast cancer increased from 1.00 (reference) to 1.06 (95% CI, 0.56–1.99), 1.50 (95% CI, 0.79–2.83), and 2.32 (95% CI, 1.24–4.41) for the lowest to highest quartiles of PGE-M, and such associations were stronger among those who were diagnosed with cancer within the first four years of sample collection. No apparent association was observed among overweight postmenopausal women (BMI ≥ 25 kg/m2).

Conclusion: High urinary PGE-M level was associated with elevated risk of breast cancer among normal weight, postmenopausal women.

Impact: Urinary PGE-M level may be useful for breast cancer risk assessment among normal weight, postmenopausal women. Cancer Epidemiol Biomarkers Prev; 23(12); 2866–73. ©2014 AACR.
A HGF/cMET Autocrine Loop Is Operative in Multiple Myeloma Bone Marrow Endothelial Cells and May Represent a Novel Therapeutic Target
Authors: Ferrucci Arianna , Moschetta Michele , Frassanito Maria Antonia , Berardi Simona , Catacchio Ivana , Ria Roberto , Racanelli Vito , Caivano Antonella , Solimando Antonio Giovanni , Vergara Daniele , Maffia Michele , Latorre Dominga , Rizzello Antonia , Zito Alfredo , Ditonno Paolo , Maiorano Eugenio , Ribatti Domenico , Vacca Angelo
Published: September 2014

Purpose: The aim of this study was to investigate the angiogenic role of the hepatocyte growth factor (HGF)/cMET pathway and its inhibition in bone marrow endothelial cells (EC) from patients with multiple myeloma versus from patients with monoclonal gammopathy of undetermined significance (MGUS) or benign anemia (control group).

Experimental Design: The HGF/cMET pathway was evaluated in ECs from patients with multiple myeloma (multiple myeloma ECs) at diagnosis, at relapse after bortezomib- or lenalidomide-based therapies, or on refractory phase to these drugs; in ECs from patients with MGUS (MGECs); and in those patients from the control group. The effects of a selective cMET tyrosine kinase inhibitor (SU11274) on multiple myeloma ECs' angiogenic activities were studied in vitro and in vivo.

Results: Multiple myeloma ECs express more HGF, cMET, and activated cMET (phospho (p)-cMET) at both RNA and protein levels versus MGECs and control ECs. Multiple myeloma ECs are able to maintain the HGF/cMET pathway activation in absence of external stimulation, whereas treatment with anti-HGF and anti-cMET neutralizing antibodies (Ab) is able to inhibit cMET activation. The cMET pathway regulates several multiple myeloma EC activities, including chemotaxis, motility, adhesion, spreading, and whole angiogenesis. Its inhibition by SU11274 impairs these activities in a statistically significant fashion when combined with bortezomib or lenalidomide, both in vitro and in vivo.

Conclusions: An autocrine HGF/cMET loop sustains multiple myeloma angiogenesis and represents an appealing new target to potentiate the antiangiogenic management of patients with multiple myeloma. Clin Cancer Res; 20(22); 5796–807. ©2014 AACR.
One Hormone, Two Actions: Anti- and Pro-Inflammatory Effects of Glucocorticoids
Authors: Cruz-Topete Diana , Cidlowski John A.
Published: September 2014

Glucocorticoids are essential steroid hormones secreted from the adrenal gland in response to stress. Since their discovery in the 1940s, glucocorticoids have been widely prescribed to treat inflammatory disorders and hematological cancers. In the traditional view, glucocorticoids are regarded as anti-inflammatory molecules; however, emerging evidence suggests that glucocorticoid actions are more complex than previously anticipated. The anti-inflammatory activity of glucocorticoids is attributed to the repression of pro-inflammatory genes through signal transduction by their steroid receptor, the glucocorticoid receptor (GR). The mechanisms modulating the pro-inflammatory effects of glucocorticoids are not well understood. In this review, we discuss recent findings that provide insights into the mechanism by which GR signaling can play a dual role in the regulation of the immune response. We hypothesize that these apparently opposite processes are working together to prepare the immune system to respond to a stressor (pro-inflammatory effects) and subsequently restore homeostasis (anti-inflammatory effects). Finally, we propose that determining the mechanisms which underlie the tissue-specific effects of glucocorticoids will provide an excellent tool to develop more efficient and selective glucocorticoid therapies.
Clinical Trials Documenting the Efficacy of Low-Dose Glucocorticoids in Rheumatoid Arthritis
Authors: Pincus Theodore , Cutolo Maurizio
Published: September 2014

Twelve clinical trials have documented that prednisone or prednisolone in doses of 10 mg/day or less is efficacious to improve function, maintain status and/or slow radiographic progression in patients with rheumatoid arthritis (RA). An early trial reported by de Andrade et al. [Ann Rheum Dis 1964;23:158-162] in 1964 indicated that 5 mg of prednisolone at night was preferred to 5 mg of prednisone in the morning. Harris et al. [J Rheumatol 1983;10:713-721] documented the efficacy of 5 mg/day of prednisone in a non-double-blind trial in 1983. Two important trials in the 1990s by Kirwan [N Engl J Med 1995;333:142-146] using 7.5 mg/day, and the COBRA study by Boers et al. [Lancet 1997;350:309-318] with step-down from 60 mg rapidly tapered to 5 mg/day led to strong advocacy of low-dose glucocorticoids. In 2002, the first Utrecht Study [Ann Intern Med 2002;136:1-12] indicated that 10 mg/day prednisone slowed radiographic progression, a finding confirmed and extended in 2005 by Svensson et al. [Arthritis Rheum 2005;52:3360-3370] with 7.5 mg/day, and Wassenberg et al. [Arthritis Rheum 2005;52:3371-3380] with 5 mg/day of prednisolone. In 2008, Buttgereit et al. [Lancet 2008;371:205-214] reported CAPRA-1, which documented that modified-release prednisone or prednisolone taken at bedtime led to lower morning stiffness and IL-6 levels compared to usual morning prednisone. In 2009, Pincus et al. [Ann Rheum Dis 2009;68:1715-1720] reported a withdrawal clinical trial, in which patients who took 3 mg/day were gradually withdrawn to placebo, and dropped out at a significantly higher rate than control patients who were ‘withdrawn' to prednisone. In 2012, a second Utrecht Study [Ann Intern Med 2012;156:329-339], CAMERA-II, documented that 10 mg of prednisone added to a ‘treat-to-target' strategy with methotrexate provided incremental slowing of radiographic progression. An Italian study of patients with early RA who received step-up disease-modifying antirheumatic drug therapy over 2 years plus prednisolone or not indicated higher rates of clinical remission and sustained remission associated with 7.5 mg/day of prednisolone [Arthritis Res Ther 2012; 14:R112]. The CAPRA-2 trial [Ann Rheum Dis 2013;72:204-210] documented that modified-release nighttime prednisone or prednisolone was significantly more efficacious than placebo. Taken together, these 12 clinical trials indicate that low-dose glucocorticoids prednisone or prednisolone provides symptomatic relief, improved functional status and slowing of radiographic progression for patients with RA.
Complications after Loop Ileostomy Closure: A Retrospective Analysis of 132 Patients
Authors: Poskus Eligijus , Kildusis Edvinas , Smolskas Edgaras , Ambrazevicius Marijus , Strupas Kestutis
Published: September 2014

Background: Closure of a loop ileostomy is a relatively simple procedure although many studies have demonstrated high morbidity rates following it. Methods to reduce the number of complications, such as timing of closure or different surgical closure techniques, are investigated. The aim of this study was to evaluate the experience of the Abdominal Surgery Center at Vilnius University Hospital (VUH) ‘Santariskiu klinikos' to review the complications after closure of loop ileostomy and to identify potential risk factors for postoperative complications. Methods: Data from 132 patients who underwent closure of loop ileostomy from 2003 to 2013 at the Abdominal Surgery Center of VUH were collected, including demographics, causes of ileostomy formation, additional diseases, time from creation to closure of ileostomy, anastomotic technique, duration of the operation, postoperative complications, and hospital stay after surgery. The operations were performed by 15 surgeons with varying experience assisted by surgical residents. Experience in ileostomy closure was defined by the number of procedures performed. Results: Complications occurred in 24 patients (18.2%), with 20 of them having surgical complications: bowel obstruction (9 (6.8%)), wound infection (4 (3.0%)), peritonitis due to anastomotic leak (3 (2.3%)), intra-abdominal abscess (2 (1.5%)), anastomotic leak with enterocutaneous fistula (1 (0.76%)), and bleeding (1 (0.76%)). 4 patients had non-surgical complications: postoperative diarrhea (2 (1.5%)), urinary retention (1 (0.76%)), and deep vein thrombosis (1 (0.76%)). Most complications were classified as group II according to the Clavien-Dindo classification. 2 patients died (1.5%). The anastomotic technique used did not affect the outcome. The experience of the surgeon as judged by the frequency of the procedure was the main factor affecting postoperative morbidity significantly (p = 0.03). Conclusion: Our study revealed that the rate of postoperative complications and a smooth postoperative course after the closure of ileostomy was influenced by surgical experience.
Wnt5a-Induced Wnt1-Inducible Secreted Protein-1 Suppresses Vascular Smooth Muscle Cell Apoptosis Induced by Oxidative Stress
Authors: Mill Carina , Monk Bethan Alice , Williams Helen , Simmonds Steven John , Jeremy Jamie Yancey , Johnson Jason Lee , George Sarah Jane
Published: September 2014

Objective—

Apoptosis of vascular smooth muscle cells (VSMCs) contributes to thinning and rupture of the atherosclerotic plaque fibrous cap and is thereby associated with myocardial infarction. Wnt protein activation of β-catenin regulates numerous genes that are associated with cell survival. We therefore investigated Wnt/β-catenin survival signaling in VSMCs and assessed the presence of this pathway in human atherosclerotic plaques at various stages of the disease process.

Approach and Results—

Wnt5a induced β-catenin/T-cell factor signaling and retarded oxidative stress (H
2
O
2
)–induced apoptosis in mouse aortic VSMCs. Quantification of mRNA levels revealed a >4-fold (
P
<0.05; n=9) increase in the expression of the Wnt/β-catenin responsive gene, Wnt1-inducible secreted protein-1 (WISP-1), which was dependent on cAMP response element–binding protein and sustained in the presence of H
2
O
2
. Exogenous WISP-1 significantly reduced H
2
O
2
–induced apoptosis by 43% (
P
<0.05; n=3) and was shown using silencing small interfering RNA, to be important for Wnt5a-dependent survival responses to H
2
O
2
(
P
<0.05; n=3). WISP-1 protein levels were significantly lower (≈50%) in unstable atherosclerosis compared with stable plaques (n=11 and n=14).

Conclusions—

These results indicate for the first time that Wnt5a induces β-catenin survival signaling in VSMCs via WISP-1. The deficiency of the novel survival factor, WISP-1 in intimal VSMCs of unstable coronary plaques, suggests that there is altered Wnt/β-catenin/ T-cell factor signaling with progressive atherosclerosis, and restoration of WISP-1 protein might be an effective stabilization factor for vulnerable atherosclerotic plaques.
The Effects of Diet on Occlusive Coronary Artery Atherosclerosis and Myocardial Infarction in Scavenger Receptor Class B, Type 1/Low-Density Lipoprotein Receptor Double Knockout Mice
Authors: Fuller Mark , Dadoo Omid , Serkis Viktoria , Abutouk Dina , MacDonald Melissa , Dhingani Neel , Macri Joseph , Igdoura Suleiman A. , Trigatti Bernardo L.
Published: September 2014

Objective—

Deficiency of the high-density lipoprotein receptor, scavenger receptor class B, type I (SR-BI), in apolipoprotein E knockout or hypomorphic mice, respectively, results in spontaneous or diet-inducible occlusive coronary artery (CA) atherosclerosis, myocardial infarction, and early death. Here, we examine effects of SR-BI deficiency on cardiovascular phenotypes in low-density lipoprotein receptor (LDLR) knockout mice fed different atherogenic diets.

Approach and Results—

SR-BI/LDLR double knockout and control LDLR knockout mice were fed atherogenic diets containing different amounts of fat, cholesterol, and sodium cholate. Double knockout mice fed atherogenic diets high in cholesterol exhibited significantly reduced survival compared with LDLR knockout mice fed the same diets. In addition to increased diet-accelerated aortic sinus atherosclerosis, we observed significant diet-induced CA atherosclerosis in double knockout mice and diet-dependent accumulation of platelets in CA atherosclerotic plaques. This was accompanied by substantial myocardial fibrosis in double knockout mice fed high cholesterol diets. Atherogenic diet fed double knockout mice also exhibited higher circulating cytokine levels, monocytosis with increased proportions of Ly6C
hi
and Ly6C
int
monocytes, and higher adhesion molecule expression in CA endothelial cells compared with control LDLR knockout mice.

Conclusions—

Diet-accelerated atherosclerosis and occlusive, platelet-rich CA disease in SR-BI/LDLR double knockout mice is affected by amounts of cholesterol and cholate in atherogenic diets and is accompanied by increased expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in CAs and increased Ly6C
hi
and Ly6C
int
monocytes in circulation. The increased vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in CA endothelial cells in SR-BI–deficient mice likely explains their increased susceptibility to atherosclerosis in CAs.
Immediate Changes in Stroke Lesion Volumes Post Thrombolysis Predict Clinical Outcome
Authors: Luby Marie , Warach Steven J. , Nadareishvili Zurab , Merino José G.
Published: September 2014

Background and Purpose—

We hypothesize that reversal in diffusion-weighted imaging (DWI) volume at 24 hours predicts favorable clinical outcome only if accompanied by immediate reperfusion. Our aim was to quantify the immediate DWI and mean transit time changes at 2 and 24 hours after intravenous tissue-type plasminogen activator to evaluate the effect of reperfusion and DWI change on outcome.

Methods—

Patients were selected from the Lesion Evolution in Stroke and Ischemia On Neuroimaging Project if they had an acute MRI with evaluable DWI and perfusion-weighted imaging, were treated with standard intravenous tissue-type plasminogen activator, had post-thrombolysis MRI with evaluable DWI and perfusion-weighted imaging at 2 and 24 hours and had follow-up fluid attenuated inversion recovery MRI at discharge through 90 days. A reader measured the DWI, mean transit time, and fluid attenuated inversion recovery volumes using a validated technique. A vascular neurologist scored the National Institutes of Health Stroke Scale at admit, 2, and 24 hours and the modified Rankin Scale at discharge, 5, 30, and 90 days. Favorable clinical outcome was defined as modified Rankin Scale of 0 or 1.

Results—

Seventy-one patients met the study criteria with mean (±SD) age of 71.6 (±16.4) years, 58% women, median admit National Institutes of Health Stroke Scale 9 (interquartile range, 4–18), median onset to triage 45 minutes (30–65), and median first MRI to intravenous tissue-type plasminogen activator 47 minutes (39–59). In binary multiple logistic regression analysis, younger age (odds ratio, 1.165;
P
=0.014; 95% confidence interval [CI], 1.031–1.316), lower admit National Institutes of Health Stroke Scale (odds ratio, 1.221;
P
=0.012; 95% confidence interval, 1.045–1.427), decrease in mean transit time volume at 2 hours (odds ratio, 1.021;
P
=0.031; 95% confidence interval, 1.002–1.040), and decrease in DWI volume at 24 hours (odds ratio, 1.173;
P
=0.027; 95% confidence interval, 1.018–1.351) were significant predictors of favorable clinical outcome.

Conclusions—

Reversal of the DWI volume at 24 hours because of immediate reperfusion in patients post thrombolysis is predictive of favorable clinical outcome.
Silent Information Regulator 2 Homolog 1 Counters Cerebral Hypoperfusion Injury by Deacetylating Endothelial Nitric Oxide Synthase
Authors: Hattori Yorito , Okamoto Yoko , Maki Takakuni , Yamamoto Yumi , Oishi Naoya , Yamahara Kenichi , Nagatsuka Kazuyuki , Takahashi Ryosuke , Kalaria Raj N. , Fukuyama Hidenao , Kinoshita Makoto , Ihara Masafumi
Published: September 2014

Background and Purpose—

Silent information regulator 2 homolog 1 (SIRT1) is a protein deacetylase that has been reported to suppress neurodegenerative and cardiovascular diseases in model organisms. We hypothesized that neurovascular protection is one of the diverse actions of SIRT1. This study was designed to determine whether SIRT1 protects against the consequences of cerebral hypoperfusion in vivo.

Methods—

Sirt1
-overexpressing (Sirt1-Tg) mice driven by a prion promoter and their wild-type littermates were subjected to bilateral common carotid artery stenosis using external microcoils. Using Sirt1-Tg mice, we assessed the effect of SIRT1 on cerebral blood flow, cerebral angioarchitecture, histological and ultrastructural changes, and spatial working memory at several time points. We also evaluated the effects of preadministration of SIRT1 inhibitors or endothelial nitric oxide synthase inhibitors on cerebral blood flow after bilateral common carotid artery stenosis in Sirt1-Tg mice. Levels of acetylated and nonacetylated endothelial nitric oxide synthase were measured semiquantitatively with immunoblotting.

Results—

Cerebral hypoperfusion induced by bilateral common carotid artery stenosis caused memory impairment and histological changes in wild-type littermates. However, these phenotypes were rescued in Sirt1-Tg mice, where cerebral blood flow was maintained even poststenosis. Electron microscopic analyses showed irregularities in the vascular endothelia, such as tight junction openings in wild-type mice, which were absent in Sirt1-Tg littermates. Brain endothelial nitric oxide synthase was acetylated after cerebral hypoperfusion in wild-type littermates but remained unacetylated in Sirt1-Tg mice. Moreover, treatment with SIRT1 inhibitors and endothelial nitric oxide synthase inhibitors abolished the vasculoprotective effects of SIRT1.

Conclusions—

Our results indicate that neurovascular endothelial SIRT1 potentiation upregulates the nitric oxide system and counters cerebral hypoperfusion injury. This novel cerebral blood flow–preserving mechanism offers potential molecular targets for future therapeutic intervention.
Secular Trends in Ischemic Stroke Subtypes and Stroke Risk Factors
Authors: Bogiatzi Chrysi , Hackam Daniel G. , McLeod A. Ian , Spence J. David
Published: September 2014

Background and Purpose—

Early diagnosis and treatment of a stroke improves patient outcomes, and knowledge of the cause of the initial event is crucial to identification of the appropriate therapy to maximally reduce risk of recurrence. Assumptions based on historical frequency of ischemic subtypes may need revision if stroke subtypes are changing as a result of recent changes in therapy, such as increased use of statins.

Methods—

We analyzed secular trends in stroke risk factors and ischemic stroke subtypes among patients with transient ischemic attack or minor or moderate stroke referred to an urgent transient ischemic attack clinic from 2002 to 2012.

Results—

There was a significant decline in low-density lipoprotein cholesterol and blood pressure, associated with a significant decline in large artery stroke and small vessel stroke. The proportion of cardioembolic stroke increased from 26% in 2002 to 56% in 2012 (
P
<0.05 for trend). Trends remained significant after adjusting for population change.

Conclusions—

With more intensive medical management in the community, a significant decrease in atherosclerotic risk factors was observed, with a significant decline in stroke/transient ischemic attack caused by large artery atherosclerosis and small vessel disease. As a result, cardioembolic stroke/transient ischemic attack has increased significantly. Our findings suggest that more intensive investigation for cardiac sources of embolism and greater use of anticoagulation may be warranted.
Stereomastis artuzi sp. nov., a new species of Polychelidae (Decapoda, Polychelida) described from the Sea of Marmara, Turkey
Authors: Artüz M. L. , Artüz M. L. , Kubanç C. , Artüz M. L. , Kubanç C. , Kubanç S. N.
Published: September 2014

Four specimens ofStereomastiswere caught by beam-trawl on 07 August 2011 at a depth of 1000 m in the western deep basin, around the submarine thermal vent site, along the North Anatolian Earthquake Fault, in the Sea of Marmara. These specimens appeared to belong to an as yet undescribed species. As a result,Stereomastis artuzisp. nov. is described in this study as a new species in the family Polychelidae (Decapoda, Polychelida; also alternatively classified under Decapoda, Palinura, Eryonoidea).
Regeneration of Scots pine stem after wounding
Authors: Zajączkowska Urszula
Published: September 2014

Stem regeneration after wounding was studied in 110-year-old trees of Pinus sylvestris L. over a period of 30 years. The changes of cambial surface are shown as 3D models. For construction of the models ArcGIS and geodesic Surfer programs were applied. The trees responded to stem injury by increasing the cambial activity near the wound edge. The result was longitudinal rolls or spindles which gradually covered the wounded stem surface. The successively formed tree rings changed their orientation to perpendicular with respect to the wound surface. The disturbances of wood formation near the wound edge were manifested by oblique orientation of xylem rays with respect to annual ring boundaries. The spatial distribution of the xylem ray orientation is presented on the Surfer contour maps. Near the fusion of the wound spindles there were some areas consisting of irregularly oriented xylem cells. The cellular ordering of the xylem tissue in these areas was measured by applying digital image analysis software. Measurements shown on color-coded maps revealed that the tracheid orientation (seen on tangential sections) deviated between 0 and 90 degrees from the stem axis. In some areas a circular pattern of tracheid orientation was visible. Crooked and forked tracheids were also present. These results support the view that the adaptive growth occurring in the case of deep wounding is analogous to that observed when an inanimate body is in lateral contact with a tree stem. The intensive growth and accumulation of newly deposited tissue in the wound spindles seems to be the most effective mechanism for the tree stem regeneration to restore its biomechanical and transport functions. This could be considered as an illustration of Wolff’s law that the shape of an organ follows its function.
“ … donne erano: e donne sarebbero”: Il corpo femminile come catalizzatore delle strutture narrative e delle scelte linguistiche nel Pasticciaccio
Authors: Colucci Dalila
Published: September 2014

In Quer pasticciaccio brutto de via Merulana di Carlo Emilio Gadda, il corpo femminile – smembrato ed esaminato per dettagli; ridotto alla dimensione brutalmente sessuale o emanante invece una bellezza ineffabile; costruito per contrasti e inesprimibile se non attraverso la citazione – funziona come una grande metafora del mondo e, di conseguenza, della lingua che di esso dà conto perseguendone non la spiegazione, bensì solo l’apparire. Il saggio sviluppa pertanto l’ipotesi che la sperimentazione linguistica del Pasticciaccio, così come la sua costruzione rizomatica e digressiva, venga catalizzata attraverso la rappresentazione dei profili femminili, a sua volta legata a tematiche psicologiche e sociali. Correlativo oggettivo della confusione, della molteplicità e dell’indicibilità del reale, la donna diviene cioè, per transfert letterario, microcosmo riflettente delle strutture del romanzo e delle sue caleidoscopiche scelte verbali.
New Strategy to Reduce Hypertriglyceridemia During Parenteral Nutrition While Maintaining Energy Intake
Authors: Mateu‐de Antonio Javier , Florit‐Sureda Marta
Published: September 2014

Background: Hypertriglyceridemia is a frequent metabolic complication associated with fat administration in parenteral nutrition (PN). No clear guidelines have been published on how to proceed once hypertriglyceridemia has been detected. A new strategy could be to substitute the initial fat emulsion with another emulsion with faster clearance. Our objective was to determine the effectiveness in reducing triglyceridemia values, maintaining the caloric intake, and improving nutrition parameters in patients who had moderate hypertriglyceridemia during PN when an olive oil–based fat emulsion (OOFE) was substituted with a multiple‐source oil fat emulsion (MOFE). We also assessed the safety of this substitution in hepatic and glycemic profiles. Materials and Methods: We performed a retrospective, observational study that included 38 adult patients to whom OOFE in PN was substituted with MOFE when moderate hypertriglyceridemia (≥250–400 mg/dL) was detected. Results: Triglyceridemia values decreased in 36 (94.7%) patients. The mean reduction was 71 (88–22) mg/dL. Fat load was slightly reduced after substitution (–0.14 [–0.23 to 0] g/kg/d; P < .001), but total caloric intake increased from 22.5 (19.7–25.1) to 23.1 (19.8–26.8) kcal/kg/d (P = .053). After substitution, nutrition parameters improved, liver parameters remained unchanged, and insulin requirements increased. Conclusion: The substitution of OOFE with MOFE in patients with moderate hypertriglyceridemia during PN resulted in a reduction in triglyceridemia values of about 70 mg/dL. That allowed maintaining the caloric intake and improved nutrition parameters without affecting the hepatic profile. For some patients, insulin requirements increased moderately.