bluuebunny/crossref_metadata_2025 huggingface dataset:
A high-affinity and specific carrier-mediated mechanism for uptake of thiamine pyrophosphate by human colonic epithelial cells
Authors: Nabokina Svetlana M. , Said Hamid M.
Published: May 2012

All mammals require exogenous sources of thiamine (vitamin B1), as they lack the ability to synthesize the vitamin. These sources are dietary and bacterial (the latter is in reference to the vitamin, which is synthesized by the normal microflora of the large intestine). Bacterially generated thiamine exists in the free, as well as the pyrophosphorylated [thiamine pyrophosphate (TPP)], form. With no (or very little) phosphatase activity in the colon, we hypothesized that the bacterially generated TPP can also be taken up by colonocytes. To test this hypothesis, we examined [3H]TPP uptake in the human-derived, nontransformed colonic epithelial NCM460 cells and purified apical membrane vesicles isolated from the colon of human organ donors. Uptake of TPP by NCM460 cells occurred without metabolic alterations in the transported substrate and 1) was pH- and Na+-independent, but energy-dependent, 2) was saturable as a function of concentration (apparent Km= 0.157 ± 0.028 μM), 3) was highly specific for TPP and not affected by free thiamine (or its analogs) or by thiamine monophosphate and unrelated folate derivatives, 4) was adaptively regulated by extracellular substrate (TPP) level via what appears to be a transcriptionally mediated mechanism(s), and 5) appeared to be influenced by an intracellular Ca2+/calmodulin-mediated regulatory pathway. These findings suggest the involvement of a carrier-mediated mechanism for TPP uptake by colonic NCM460 cells, which was further confirmed by results from studies of native human colonic apical membrane vesicles. The results also suggest that the bacterially synthesized TPP in the large intestine is bioavailable and may contribute to overall body homeostasis of vitamin B1 and, especially, to the cellular nutrition of the local colonocytes.
Low-intensity exercise can increase muscle mass and strength proportionally to enhanced metabolic stress under ischemic conditions
Authors: Takada Shingo , Okita Koichi , Suga Tadashi , Omokawa Masashi , Kadoguchi Tomoyasu , Sato Takashi , Takahashi Masashige , Yokota Takashi , Hirabayashi Kagami , Morita Noriteru , Horiuchi Masahiro , Kinugawa Shintaro , Tsutsui Hiroyuki
Published: May 2012

Skeletal muscle bulk and strength are becoming important therapeutic targets in medicine. To increase muscle mass, however, intensive, long-term mechanical stress must be applied to the muscles, and such stress is often accompanied by orthopedic and cardiovascular problems. We examined the effects of circulatory occlusion in resistance training combined with a very low-intensity mechanical load on enhancing muscular metabolic stress and thereby increasing muscle bulk. Muscular metabolic stress, as indicated by the increases in inorganic phosphate (Pi) and a decrease in intramuscular pH, was evaluated by31P-magnetic resonance spectroscopy during unilateral plantar-flexion at 20% of the one-repetition maximum (1-RM) with circulatory occlusion for 2 min in 14 healthy, male untrained participants (22 yr) at baseline. Participants performed two sets of the same exercise with a 30-s rest between sets, 2 times/day, 3 days/wk, for 4 wk. The muscle cross-sectional area (MCA) of the plantar-flexors and the 1-RM were measured at baseline and after 2 and 4 wk of training. MCA and 1-RM were significantly increased after 2 and 4 wk ( P < 0.05, respectively). The increase in MCA at 2 wk was significantly ( P < 0.05) correlated with the changes in Pi( r = 0.876) and intramuscular pH ( r = 0.601). Furthermore, the increases in MCA at 4 wk and 1-RM at 2 wk were also correlated with the metabolic stress. Thus enhanced metabolic stress in exercising muscle is a key mechanism for favorable effects by resistance training. Low-intensity resistance exercise provides successful outcomes when performed with circulatory occlusion, even with a short training period.
Locally measured shear moduli of pulmonary tissue and global lung mechanics in mechanically ventilated rats
Authors: Schwenninger David , Runck Hanna , Schumann Stefan , Haberstroh Jörg , Guttmann Josef
Published: May 2012

This study was aimed at measuring shear moduli in vivo in mechanically ventilated rats and comparing them to global lung mechanics. Wistar rats ( n = 28) were anesthetized, tracheally intubated, and mechanically ventilated in supine position. The animals were randomly assigned to the healthy control or the lung injury group where lung injury was induced by bronchoalveolar lavage. The respiratory system elastance Ers was analyzed based on the single compartment resistance/elastance lung model using multiple linear regression analysis. The shear modulus (G) of alveolar parenchyma was studied using a newly developed endoscopic system with adjustable pressure at the tip that was designed to induce local mechanostimulation. The data analysis was then carried out with an inverse finite element method. G was determined at continuous positive airway pressure (CPAP) levels of 15, 17, 20, and 30 mbar. The resulting shear moduli of lungs in healthy animals increased from 3.3 ± 1.4 kPa at 15 mbar CPAP to 5.8 ± 2.4 kPa at 30 mbar CPAP ( P = 0.012), whereas G was ∼2.5 kPa at all CPAP levels for the lung-injured animals. Regression analysis showed a negative correlation between G and relative Ers in the control group ( r = −0.73, P = 0.008 at CPA P = 20 mbar) and no significant correlation in the lung injury group. These results suggest that the locally measured G were inversely associated with the elastance of the respiratory system. Rejecting the study hypothesis the researchers concluded that low global respiratory system elastance is related to high local resistance against tissue deformation.
Cystathionine β-synthase deficiency causes infertility by impairing decidualization and gene expression networks in uterus implantation sites
Authors: Nuño-Ayala Mario , Guillén Natalia , Arnal Carmen , Lou-Bonafonte José M. , de Martino Alba , García-de-Jalón Jose-Antonio , Gascón Sonia , Osaba Lourdes , Osada Jesús , Navarro María-Angeles
Published: May 2012

Hyperhomocysteinemia has been reported in human reproduction as a risk factor for early pregnancy loss, preeclampsia, and congenital birth defects like spina bifida. Female infertility was also observed in cystathionine beta synthase-deficient mice ( Cbs-KO) as an animal model for severe hyperhomocysteinemia. The aim for the present research was to elucidate the time-point of pregnancy loss and to pinpoint gene and cellular changes involved in the underlying pathological mechanism. By mating 90-day-old wild-type and Cbs-KO female mice with their homologous male partners, we found that pregnancy loss in Cbs-KO occurred between the 8th and 12th gestation day during placenta formation. DNA microarrays were carried out on uterus from implantation and interimplantation samples obtained on day 8. The results allowed us to select genes potentially involved in embryo death; these were individually confirmed by RT-qPCR, and their expressions were also followed throughout pregnancy. We found that changes in expression of Calb1, Ttr, Expi, Inmt, Spink3, Rpgrip1, Krt15, Mt-4, Gzmc, Gzmb, Tdo2, and Afp were important for pregnancy success, since a different regulation in Cbs-KO mice was found. Also, differences in relationships among selected genes were observed, indicating a dysregulation of these genes in Cbs-KO females. In conclusion, our data provide more information on the gene expression cascade and its timely regulated process required for a successful pregnancy. In addition, we unveil new potential avenues to explore further investigations in pregnancy loss.
Fallopian Tube Reanastomosis by Laparotomy versus Laparoscopy: A Meta-Analysis
Authors: la Grange J. , Kruger T.F. , Steyn D.W. , van der Merwe J.P. , Siebert I. , Matsaseng T. , Viola M.I.
Published: May 2012

Objective: To compare efficacy of sterilization reversals by laparotomy versus laparoscopy. Design: Meta-analysis. Search Strategy: Electronic searches were carried out for randomized controlled trials and retrospective and prospective clinical studies. Search engines such as PubMed, Science Direct, Medline and the Cochrane database were made use of. Our restrictions were English human studies published from 1989 to January 2010. Interventions: Microsurgical tubal reanastomosis performed comparing laparoscopy with laparotomy using a microsurgical technique. Outcome Measures:Primary: overall pregnancy rates, including positive clinical pregnancy, intrauterine and ectopic pregnancy rates. Secondary: surgery time. Results: Three retrospective comparative studies were retrieved from international data that investigated laparotomy versus laparoscopy. A total number of 184 patients were included, 88 and 96 respectively undergoing laparoscopy and laparotomy. Pregnancy rates achieved by laparoscopy ranged from 65 to 80.5% (mean 74.43%) and by laparotomy from 70 to 80% (mean 71.33%). A subanalysis of two of the three comparative studies show that laparoscopy reversal surgery requires a statistically significant longer operative time than does laparotomy (p < 0.00001). Conclusions: There is no difference between the laparoscopy and laparotomy approach to tubal reanastomosis when regarding overall pregnancy rates, intrauterine and ectopic pregnancy rates.
Low-Frequency rTMS over Right Dorsolateral Prefrontal Cortex in the Treatment of Resistant Depression: Cognitive Improvement Is Independent from Clinical Response, Resting Motor Threshold Is Related to Clinical Response
Authors: Pallanti S. , Di Rollo A. , Antonini S. , Cauli G. , Hollander E. , Quercioli L.
Published: May 2012

Background: Clinical studies have shown that repetitive transcranial magnetic stimulation (rTMS) is effective in a certain percentage of treatment-resistant depression (TRD). The left dorsolateral prefrontal cortex (DLPFC) 10 Hz rTMS stimulation received FDA approval in 2008, although different rTMS protocols have also shown their effectiveness in reducing depressive symptoms. We investigated the clinical, cognitive and neurophysiologic effects of a 3 weeks’ protocol of low-frequency rTMS applied over the right DLPFC in resistant depression. Methods: Twenty-eight patients with TRD (age range 28–55) received low-frequency rTMS (1 Hz) over the right DLPFC in a 3-week open trial. Hamilton scales for depression and anxiety, Corsi block-tapping test, phonemic verbal fluency, right and left resting motor thresholds were evaluated in each subject over the trial period. Results: At the end of the trial 42.9% of the subjects were considered as responders. A significant reduction of both HAMD (p < 0.001) and HAMA (p < 0.01) total scores was observed. At the 3rd week, the performances in Corsi test (p < 0.02) and phonemic verbal fluency (p = 0.065) were improved independently from depressive symptoms variation. At the end of the rTMS protocol, a significantly decreased left hemisphere resting motor threshold was registered (p < 0.01), while right hemisphere resting motor threshold did not show significant variation. Conclusion: Low-frequency rTMS over the right DLPFC appeared effective in 42.9% of depressive resistant subjects in this sample. A significant decrease in left hemisphere resting motor threshold was observed only in responders, while a trend for improvement in cognitive function has been found and appeared independent from clinical response.
Frequency, Risk Factors and Prognosis of Postoperative Hyperbilirubinemia after Heart Valve Surgery
Authors: Nishi Hiroyuki , Sakaguchi Taichi , Miyagawa Shigeru , Yoshikawa Yasushi , Fukushima Satsuki , Saito Shunsuke , Ueno Takayoshi , Kuratani Toru , Sawa Yoshiki
Published: May 2012

Objectives: Despite recent advances in cardiovascular surgery, hyperbilirubinemia after heart valve surgery occurs often and the mechanism is not well clarified. We evaluated the incidence and nature of postoperative hyperbilirubinemia in heart valve surgery patients to analyze its risk factors and to identify its clinical significance for associated morbidity and mortality. Methods: We investigated 334 consecutive patients who underwent heart valve surgery. Postoperative hyperbilirubinemia was defined as total serum bilirubin concentration greater than 3 mg/dl at any postoperative measurement point. Results: Postoperative hyperbilirubinemia developed in 63 patients (19.0%) and was associated with greater in-hospital mortality (15.9 vs. 1.5%, p < 0.01). Univariate analysis revealed congestive heart failure history, cardiogenic shock, infective endocarditis, preoperative liver dysfunction, longer cardiopulmonary bypass time and transfusion as significantly related to postoperative hyperbilirubinemia. In multivariate analysis, preoperative liver dysfunction [odds ratio (OR) 6.5, p < 0.05] and longer cardiopulmonary bypass time (OR 1.007, p < 0.01) were independent predictors. In postoperative hyperbilirubinemia patients, preoperative New York Heart Association status and history of heart failure were associated with outcome. Conclusions: Postoperative hyperbilirubinemia remains common in patients undergoing heart valve surgery and is associated with a high rate of in-hospital mortality. For patients with heart failure or liver dysfunction, meticulous operative management is required to reduce cardiopulmonary bypass time and transfusion.
Surgical Trauma and Postoperative Immune Dysfunction
Authors: Menges P. , Kessler W. , Kloecker C. , Feuerherd M. , Gaubert S. , Diedrich S. , van der Linde J. , Hegenbart A. , Busemann A. , Traeger T. , Cziupka K. , Heidecke C.-D. , Maier S.
Published: May 2012

Background: In postoperative sepsis, mortality is increased due to the surgically induced immune dysfunction. Further causes of this traumatic effect on the immune system include burn injuries and polytrauma, as well as endogenous traumata like stroke. Several animal models have been defined to analyse the characteristics of trauma-induced immune suppression. This article will correlate our results from animal studies and clinical observations with the recent literature on postoperative immune suppression. Methods: The previously described model of surgically induced immune dysfunction (SID) was performed in mice by laparotomy and manipulation of the small intestine in the antegrade direction. Blood samples were collected 6 and 72 h following SID to analyse the white blood cell count and corticosterone levels. To assess the postoperative immune status in humans, we analysed expression of HLA-DR on monocytes of 118 patients by flow cytometry prior to and 24, 48 and 72 h after surgery. Results: The postoperative immune suppression in our SID model is characterised by lymphocytopenia and significantly increased corticosterone levels in mice dependent on the degree of surgical trauma. This is comparable to the postoperative situation in humans: major and especially long-lasting surgery results in a significantly reduced expression of HLA-DR on circulating monocytes. Previous studies describe a similar situation following burn injury and endogenous trauma, i.e. stroke. Conclusions: We suggest the completion of our previously published sepsis classification due to the immune status at the onset of sepsis: type A as the spontaneously acquired sepsis and type B as sepsis in trauma-induced pre-existing immune suppression.
Oxidized Low-Density Lipoprotein Antigen Transport Induces Autoimmunity in the Renal Tubulointerstitium
Authors: Satirapoj Bancha , Bruhn Kevin W. , Nast Cynthia C. , Wang Ying , Dai Tiane , LaPage Janine , Wu Xiwei , Natarajan Rama , Adler Sharon G.
Published: May 2012

Background/Aims: Chronic kidney disease involves inflammation/oxidative stress, which contributes to progressive kidney injury. Methods: Male Sprague-Dawley rats underwent 5/6 nephrectomy (Nx) or sham Nx and were sacrificed after 2 days, 2 weeks and 4 weeks. Microarray analysis expression sets over time suggested the evolution of renal lymphocyte infiltration and antigen-presenting cell (APC) activation after 5/6Nx. RT-PCR analysis also confirmed the migration and activation of lymphocytes and APCs through the upregulation of CD3, CXCR3/CXCL10 and CCR7/CCL19 mRNA in remnant kidney (RK). Purified T lymphocytes from spleen and unilateral ureteral obstruction (UUO) kidney were incubated with oxidized low-density lipoprotein (Ox-LDL)-treated major histocompatibility complex class II (MHC II)-expressing APCs. Culture supernatant was collected for mouse IFN-γ ELISA and cell proliferation was measured. Results: Ox-LDL deposited predominantly in renal tubulointerstitial areas of RK, increased over time, and co-stained with lectin-like Ox-LDL receptor in affected renal tubular cells. Both Ox-LDL and renal-specific glycoprotein Tamm-Horsfall protein were identified in renal lymph nodes. Cells co-staining for major MHC II and Ox-LDL were observed in RK and draining renal lymph nodes after 5/6Nx. Similarly, Ox-LDL was also present in tubules after UUO, CD3-positive T cells were present in the interstitium, and Ox-LDL-treated MHC II-expressing APCs induced proliferation and IFN-γ production in renal tubulointerstitial T lymphocytes isolated from kidneys after UUO. Conclusions: These data demonstrate that the tubulointerstitial inflammatory infiltrate that accompanies chronic kidney disease reflects, at least in part, the development of autoimmunity to novel antigens generated during renal injury.
Exogenous Inflammatory Acne due to Combined Application of Cosmetic and Facial Rubbing
Authors: Seneschal Julien , Kubica Emeline , Boursault Lucile , Stokkermans Josette , Labreze Christine , Milpied Brigitte , Ezzedine Khaled , Taïeb Alain
Published: May 2012

Background: Exogenous acne refers to acneiform lesions due to external factors such as cosmetic agents, exposure to various oils, skin rubbing or friction or chloracne, now better called metabolizing acquired dioxin-induced skin hamartoma (MADISH). Here we report a new form of severe inflammatory exogenous acne due to the association of two factors: facial friction with cosmetic agents. Observations: A 15-, 17- and 19-year-old female presented at the department with severe inflammatory acne. In all cases, the face had been strongly rubbed in a compulsory manner in the previous weeks with cosmetic agents. The disease has not responded to various conventional acne treatments and was well controlled by a combination of oral corticosteroids and low-dose isotretinoin. Conclusion: Because cosmetic face friction as a cosmetic care becomes more and more fashionable, dermatologists should be aware of this severe clinical condition, which can occur in patients without a personal history of acne.
Variegated Dermoscopy of in situ Melanoma
Authors: Seidenari Stefania , Bassoli Sara , Borsari Stefania , Ferrari Chiara , Giusti Francesca , Ponti Giovanni , Tomasini Carlo , Magnoni Cristina
Published: May 2012

Background: Melanomas in situ (MIS) are difficult to diagnose, lacking well-established dermoscopic descriptors. Objective: The aim of this study was to improve the identification of early melanomas describing the variegated dermoscopic features of MIS and their correlation with demographic and clinical aspects. Methods: Dermoscopic images of 114 histologically proven MIS were evaluated by 3 expert dermoscopists and classified into their main dermoscopic patterns. Dermoscopic features were also considered for their correlation with clinical parameters. Results: Eight different dermoscopic subtypes of MIS were identified: reticular grey-blue (27.2%), reticular (21.1%), multicomponent (20.2%), island (10.5%), spitzoid (7%), inverse network (6.1%), ‘net-blue globules’ (5.3%) and globular (2.6%). Clinical characteristics of lesions and patients varied according to the different dermoscopic groups. Conclusion: We hypothesize that the different dermoscopic subgroups of MIS correspond to lesions with a different origin and, possibly, various patterns of growth and a different biological behaviour.
Network meta-analysis of prasugrel, ticagrelor, high- and standard-dose clopidogrel in patients scheduled for percutaneous coronary interventions
Authors: Moertl Deddo , Chen Li , Coyle Doug , Wells George A. , Steiner Sabine
Published: May 2012

Since novel antiplatelet treatments (prasugrel, ticagrelor, high-dose clopidogrel) have been predominantly tested against standard-dose clopidogrel, data on direct comparisons between these therapies are scarce. We therefore indirectly compared their efficacy and safety in patients undergoing percutaneous coronary intervention. Electronic databases were searched systematically to identify head-to-head randomised controlled trials (RCTs). Network meta-analysis was performed using generalised linear mixed models with adjustment for length of follow-up. Findings were corroborated by mixed treatment comparison through Bayesian methods. Fourteen RCTs were identified and included in the analysis (high- vs. standard-dose clopidogrel: 9 trials, prasugrel vs. high-dose clopidogrel: 2 trials, prasugrel vs. standard-dose clopidogrel: 2 trials, ticagrelor vs. standard-dose clopidogrel: 1 trial). No significant differences were found for efficacy outcomes except for stent thrombosis favouring prasugrel (vs. ticagrelor: odds ratio [OR] 0.63, 95% confidence interval [CI]: 0.42, 0.94; vs. high-dose clopidogrel: OR 0.70, 95%CI: 0.48, 1.01). Prasugrel exhibited a similar bleeding risk as high-dose clopidogrel, but more major (OR 1.43, 95%CI 1.07, 1.90) and major or minor bleeding (OR 1.36, 95%CI 1.09, 1.69) compared to ticagrelor. Ticagrelor was also associated with less major or minor bleeding compared to high-dose clopidogrel (OR 0.81, 95%CI 0.69, 0.96). No differences were seen for non CABG-related major bleeding between the three strategies. Results were corroborated in a subgroup analysis comprising only patients with acute coronary syndromes. In the absence of head-to-head clinical trials, network meta-analysis suggests potentially relevant differences in efficacy and bleeding risk among novel antiplatelet treatments and may thereby advance understanding of their differential therapeutic properties.
Lethal factor VII deficiency due to novel mutations in the F7 promoter: Functional analysis reveals disruption of HNF4 binding site
Authors: Chafa Ouerdia , Tapon-Bretaudière Jacqueline , Claustres Mireille , Taulan Magali , Giansily-Blaizot Muriel , Lopez Estelle , Viart Victoria
Published: May 2012

Hereditary factor VII (FVII) deficiency is a rare autosomal recessive disorder. Deleterious mutations that prevent the synthesis of any amount of functional FVII have been associated with life-threatening haemorrhage in neonates. Here we report two infants, of Maghrebian origin, who suffered a fatal spontaneous cerebral haemorrhage. Investigation of the molecular basis for their severe FVII deficiency revealed novel mutations in a homozygous state within the F7 gene promoter: a single nucleotide substitution (c.-65G>C) and a 2bp deletion (c.-60_-59delTT). To determine whether these promoter variants were responsible for the FVII deficiency, computer–assisted sequence analyses were performed. The data predicted a disrupted binding of both HNF4 and COUP-TF transcription factors with each variant. Concordantly, experimental results revealed an altered HNF4-induced transactivation in the promoter mutated variants. The execution of functional tests is critical to ensuring a complete understanding of the effect of any promoter mutant on FVII deficiency. Only then can an accurate molecular diagnosis be made and further genetic counselling and prenatal diagnosis be offered.
Reactive leptin resistance and the profile of platelet activation in acute ischaemic stroke patients
Authors: Michalak Slawomir , Dworacki Grzegorz , Siewiera Karolina , Kaczmarek Mariusz , Watala Cezary , Kozubski Wojciech , Lukasik Maria
Published: May 2012

Summary

Leptin is an adipokine that in vitro enhances agonist-induced platelet aggregation and adipokine expression. Hyperleptinaemia represents a risk factor for cardiovascular disease. We conducted a prospective evaluation of the potential link between blood platelet activation and plasma leptin levels in post-stroke patients. Using five-colour flow cyto-metry, the platelet surface expression of CD40L, CD62P, the subpopulations of monocyte-platelet aggregates and platelet-derived microparticles (PMPs) as well as the plasma leptin, soluble leptin receptor (sOb-R), leptin/sOb-R ratio, the plasma adiponectin, and leptin/adiponectin ratio were assessed in 98 stroke patients on the first (V0), 10th (V1) and 90th (V2) day after stroke and once in 78 age-, gender- and vascular risk factor-matched disease controls. We demonstrated that at V0 leptin resistance, defined as leptin/sOb-R ratio, was higher than in the controls [1.1 (0.5–1.8 vs. 0.5 (0.2–1.1); p=0.02]. After adjustment according to the factors which influence platelet activation, we confirmed the relationship between percentage of circulating PMPs and plasma leptin level (B=0.18; p=0.02) or the leptin/sOb-R ratio (B=0.23; p=0.02) in normal-weight subjects in the acute phase of stroke. No correlation could be demonstrated between the adipokine parameters and the percentage of monocyte-platelet aggregates or expression of platelet pro-inflammatory glycoproteins. In conclusion, formation of PMPs on the first day following an ischaemic stroke shows a positive correlation with leptin levels and with resistance to leptin. Leptin level does not seem to affect the expression of platelet surface proinflammatory glycoproteins.
Analytical challenges and technical limitations in assessing circulating MiRNAs
Authors: Mayr Manuel , Zampetaki Anna
Published: May 2012

MiRNAs are emerging as promising biomarkers in cardiovascular diseases and may constitute a novel mechanism of intercellular communication. Accurate quantification of circulating miRNAs is essential. A variety of technological approaches and platforms have been developed with increased sensitivity and specificity for the detection and quantification of circulating miRNAs. In this review, we focus on the technical aspects and discuss the analytical challenges in profiling circulating miRNAs.
Anticoagulation in ambulatory cancer patients with no indication for prophylactic or therapeutic anticoagulation
Authors: Pishko Allyson M. , Smith Kenneth J. , Ragni Margaret V.
Published: May 2012

Venous thromboembolism (VTE) occurs frequently in cancer patients and is a major cause of mortality. Although anticoagulation (AC) may have anti-tumour effects, it is recommended in cancer patients only for indications unrelated to these effects. A Markov model was constructed to estimate when prophylactic AC, given during four months of chemotherapy following a new cancer diagnosis, would be economically reasonable in ambulatory cancer patients with no VTE history. Risks and costs of major and minor bleeding, VTE, and death were obtained from the literature, including a 2011 Cochrane review of AC in cancer inpatients with no conventional indication. In the model, AC was low-molecular-weight-heparin (LMWH), and effects were modeled over a 24-month period. Model outputs were quality-adjusted life years (QALY) and the incremental cost-effectiveness ratio (ICER). In the base case analysis, when prophylactic AC had a two-year relative mortality risk of 0.92, there was a gain of 0.0354 QALY, for an ICER of $90,893/QALY gained, compared with no AC. In sensitivity analyses, AC prophylaxis cost less than $100,000/QALY, if two-year mortality exceeded 75%, or if AC costs were less than $1,076 per month, or if LMWH relative mortality risk was less than 0.927. Results were not sensitive to variation in VTE relative risk on AC, nor to major or minor bleeding risk on AC. A probabilistic sensitivity analysis also favoured prophylactic AC. In conclusion, prophylactic LMWH given to decrease cancer-related mortality, with no conventional indication, appears economically reasonable if its suggested mortality benefit is confirmed in future trials.
Blocking Toll-Like Receptors 7 and 9 Reduces Postinterventional Remodeling via Reduced Macrophage Activation, Foam Cell Formation, and Migration
Authors: Karper Jacco C. , Ewing Mark M. , Habets Kim L.L. , de Vries Margreet R. , Peters Erna A.B. , van Oeveren-Rietdijk Annemarie M. , de Boer Hetty C. , Hamming Jaap F. , Kuiper Johan , Kandimalla Ekambar R. , La Monica Nicola , Jukema J. Wouter , Quax Paul H.A.
Published: May 2012

Objective—

The role of toll-like receptors (TLRs) in vascular remodeling is well established. However, the involvement of the endosomal TLRs is unknown. Here, we study the effect of combined blocking of TLR7 and TLR9 on postinterventional remodeling and accelerated atherosclerosis.

Methods and Results—

In hypercholesterolemic apolipoprotein E*3-Leiden mice, femoral artery cuff placement led to strong increase of TLR7 and TLR9 presence demonstrated by immunohistochemistry. Blocking TLR7/9 with a dual antagonist in vivo reduced neointimal thickening and foam cell accumulation 14 days after surgery by 65.6% (
P
=0.0079). Intima/media ratio was reduced by 64.5% and luminal stenosis by 62.8%. The TLR7/9 antagonist reduced the arterial wall inflammation, with reduced macrophage infiltration, decreased cytoplasmic high-mobility group box 1 expression, and altered serum interleukin-10 levels. Stimulation of cultured macrophages with TLR7 and TLR9 ligands enhanced tumor necrosis factor-α expression, which is decreased by TLR7/9 antagonist coadministration. Additionally, the antagonist abolished the TLR7/9-enhanced low-density lipoprotein uptake. The antagonist also reduced oxidized low-density lipoprotein–induced foam cell formation, most likely not via decreased influx but via increased efflux, because CD36 expression was unchanged whereas interleukin-10 levels were higher (36.1±22.3 pg/mL versus 128.9±6.6 pg/mL;
P
=0.008).

Conclusion—

Blocking TLR7 and TLR9 reduced postinterventional vascular remodeling and foam cell accumulation indicating TLR7 and TLR9 as novel therapeutic targets.
Chronic Administration of Oral Vasopressin Type 2 Receptor Antagonist Tolvaptan Exerts Both Myocardial and Renal Protective Effects in Rats With Hypertensive Heart Failure
Authors: Morooka Hanako , Iwanaga Yoshitaka , Tamaki Yodo , Takase Toru , Akahoshi Yasumitsu , Nakano Yoshimasa , Fujiki Hiroyuki , Miyazaki Shunichi
Published: May 2012

Background—

Although recent clinical trials have demonstrated the efficacy of the oral vasopressin (AVP) type 2 receptor (V2R) antagonist tolvaptan, its long-term effects on the myocardium and kidney in heart failure (HF) are not clear. We examined the chronic effects of tolvaptan administration on both the myocardium and kidney in a rat hypertensive HF model.

Methods and Results—

Not only circulating AVP level but also myocardial AVP and V1a receptor (V1aR) expressions, renal V1aR, and V2R expressions were significantly upregulated during the transition to HF. The animals were chronically treated with low-dose or high-dose (HD) tolvaptan or vehicle from the left ventricular (LV) hypertrophic stage. Chronic tolvaptan treatment persistently increased urine volume but did not affect blood pressure. In the HD group, the animal survival significantly improved (log-rank test,
P
<0.01). At the HF stage, the progression of LV dysfunction was prevented and lung congestion was suppressed. Activation of atrial natriuretic peptide, endothelin-1, AVP, and V1aR mRNA levels were significantly suppressed in the LV myocardium. Meanwhile, renal histopathologic damage was ameliorated and renal function was improved in the HD group at the HF stage. Concomitantly, not only activation of aquaporin-2 but also those of V2R, V1aR, renin, and endothelin-1 in the kidney were significantly suppressed (all
P
<0.05).

Conclusions—

These results indicate that chronic tolvaptan treatment has beneficial effects by preventing not only the progression of LV dysfunction but also that of renal injury in hypertensive rats with HF. The underlying mechanism may be related to the suppression of myocardial and renal neurohumoral activation.
Relation Between Change in Blood Pressure in Acute Stroke and Risk of Early Adverse Events and Poor Outcome
Authors: Sandset Else C. , Murray Gordon D. , Bath Philip M.W. , Kjeldsen Sverre E. , Berge Eivind
Published: May 2012

Background and Purpose—

The Scandinavian Candesartan Acute Stroke Trial (SCAST) found no benefits of candesartan in acute stroke. In the present analysis we aim to investigate the effect of change in blood pressure during the first 2 days of stroke on the risk of early adverse events and poor outcome.

Methods—

SCAST was a multicenter, randomized controlled, double-blind trial of candesartan in acute stroke. The trial recruited 2029 patients presenting within 30 hours of acute stroke and with systolic blood pressure (SBP) ≥140 mm Hg. Treatment was given for 7 days. Change in blood pressure was defined as the difference in SBP between baseline and Day 2 and was used to divide patients into groups with increase/no change, a small decrease, moderate decrease, or large decrease in SBP. The primary effect parameter was early adverse events (recurrent stroke, stroke progression, and symptomatic hypotension) during the first 7 days, analyzed using logistic regression, with the group with a small decrease in SBP as the reference group. Secondary effect parameters were neurological status at 7 days and functional outcome at 6 months.

Results—

Patients with a large decrease or increase/no change in SBP had a significantly increased risk of early adverse events relative to patients with a small decrease (OR, 2.08; 95% CI, 1.19–3.65 and OR, 1.96; 95% CI, 1.13–3.38, respectively). Patients with an increase/no change in SBP had a significantly increased risk of poor neurological outcome as compared with the other groups (
P
=0.001). No differences were observed in functional outcome at 6 months.

Conclusions—

Our findings support the suggestion from SCAST that blood pressure reduction may be harmful and that routine blood pressure-lowering treatment should probably be avoided in the acute phase.

Clinical Trial Information—

Clinical Trial Registration:
www.clinicaltrials.gov
. Unique identifier: NCT00120003.
Poststroke Disposition and Associated Factors in a Population-Based Study
Authors: Béjot Yannick , Troisgros Odile , Gremeaux Vincent , Lucas Brigitte , Jacquin Agnès , Khoumri Catia , Aboa-Eboulé Corine , Benaïm Charles , Casillas Jean-Marie , Giroud Maurice
Published: May 2012

Background and Purpose—

The organization of poststroke care will be a major challenge in coming years. We aimed to assess hospital disposition after stroke and its associated factors in clinical practice.

Methods—

All cases of stroke from 2006 to 2010 were identified from the population-based Stroke Registry of Dijon, France. Demographic features, risk factors, and prestroke treatments were recorded. Admission stroke severity was assessed using the National Institutes of Health Stroke Scale score. At discharge, we collected dementia, disability using the modified Rankin Scale, length of stay, and hospital disposition (home, rehabilitation, convalescent home, and nursing home). Multivariate analyses were performed using logistic regression models to identify associated factors of postdischarge disposition.

Results—

Of the patients with 1069 stroke included, 913 survived acute care. Among them, 433 (47.4%) returned home, whereas 206 (22.6%) were discharged to rehabilitation, 134 (14.7%) were admitted to a convalescent home, and 140 (15.3%) to a nursing home. Old patients, those under anticoagulants before stroke, those with severe stroke on admission, severe disability at discharge, dementia, or prolonged length of stay were less likely to return home. Moreover, advanced age, severe initial stroke, severe disability at discharge, and dementia were associated with admission to convalescent and nursing homes rather than rehabilitation centers.

Conclusion—

This population-based study demonstrated that postdischarge destinations are associated with several factors. Our findings may be useful to establish health policy concerning the organization of poststroke care.
Nonstationary Trapped Lee Waves Generated by the Passage of an Isolated Jet
Authors: Hills Matthew O. G. , Durran Dale R.
Published: May 2012

The behavior of nonstationary trapped lee waves in a nonsteady background flow is studied using idealized three-dimensional (3D) numerical simulations. Trapped waves are forced by the passage of an isolated, synoptic-scale barotropic jet over a mountain ridge of finite length. Trapped waves generated within this environment differ significantly in their behavior compared with waves in the more commonly studied two-dimensional (2D) steady flow. After the peak zonal flow has crossed the terrain, two disparate regions form within the mature wave train: 1) upwind of the jet maximum, trapped waves increase their wavelength and tend to untrap and decay, whereas 2) downwind of the jet maximum, wavelengths shorten and waves remain trapped. Waves start to untrap approximately 100 km downwind of the ridge top, and the region of untrapping expands downwind with time as the jet progresses, while waves downstream of the jet maximum persist. Wentzel–Kramers–Brillouin (WKB) ray tracing shows that spatial gradients in the mean flow are the key factor responsible for these behaviors. An example of real-world waves evolving similarly to the modeled waves is presented.

As expected, trapped waves forced by steady 2D and horizontally uniform unsteady 3D flows decay downstream because of leakage of wave energy into the stratosphere. Surprisingly, the downstream decay of lee waves is inhibited by the presence of a stratosphere in the isolated-jet simulations. Also unexpected is that the initial trapped wavelength increases quasi-linearly throughout the event, despite the large-scale forcing at the ridge crest being symmetric in time about the midpoint of the isolated-jet simulation.
Sport, spirituality and Protestantism: A historical overview
Authors: Parker Andrew , Weir J. Stuart
Published: May 2012

How, we might ask, are sport and religion connected? The truth is that, in Britain at least, these two cultural practices share a good deal of common ground primarily as a consequence of the role of Protestantism in the development of sport in Victorian times. Recent years have witnessed an increasing amount of academic discussion and debate around the sport–religion relationship. What this article aims to do is to map out the key historical features of this relationship while providing insight into the ways in which the Protestant Church continues to pursue sport as a form of outreach and ministry.
Pharmacologically Dosed Oral Glutamine Reduces Myocardial Injury in Patients Undergoing Cardiac Surgery
Authors: Sufit Alexandra , Weitzel Lindsay B. , Hamiel Christine , Queensland Kelly , Dauber Ira , Rooyackers Olav , Wischmeyer Paul E.
Published: May 2012

Background and Objective:

Glutamine (GLN) has been shown to protect against in vitro and in vivo myocardial injury. In humans, perioperative ischemia/reperfusion (I/R) injury during cardiac surgery is associated with higher morbidity and mortality. The objective of this safety and feasibility pilot trial was to determine if pharmacologically dosed, preoperative oral GLN attenuates myocardial injury in cardiac surgery patients.

Methods:

Patients undergoing elective cardiac surgery, requiring cardiopulmonary bypass, were enrolled in a randomized, double‐blind pilot trial to receive 25 g twice of oral alanyl‐glutamine (GLN; n = 7) or maltodextrin (CONT; n = 7) daily for 3 days preoperatively. Serum troponin (TROP I), creatine kinase (CK‐MB), and myoglobin (MG) were measured at multiple perioperative time points. Clinical outcomes were also recorded and assessed.

Results:

GLN therapy significantly decreased TROP I levels at 24, 48, and 72 hours postoperatively (all P < .05) vs CONT. GLN also reduced CK‐MB at 24 and 48 hours (P < .05, P < .001) vs CONT. MG was reduced at 24 hours vs control (P = .0397). GLN also significantly reduced pooled clinical complications vs CONT (P = .03).

Conclusion:

This pilot study showed that pharmacologically dosed oral GLN therapy prior to cardiac surgery was safe, well tolerated, and feasible. GLN therapy reduced myocardial injury and clinical complications in this small randomized, blinded feasibility trial. These data indicate that a larger trial of preoperative GLN therapy in patients undergoing cardiac surgery is needed to confirm clinical benefit.
Prevalence of Jugular Bulb Abnormalities and Resultant Inner Ear Dehiscence
Authors: Friedmann David R. , Eubig Jan , Winata Leon S. , Pramanik Bidyut K. , Merchant Saumil N. , Lalwani Anil K.
Published: May 2012

Objective

Jugular bulb abnormalities (JBA), including high‐riding jugular bulb (HRJB) and jugular bulb diverticulum (JBD), can erode into the inner ear. In this study, the authors investigate the prevalence and consequences of JBA and their erosion into inner ear structures using temporal bone histopathology and computed tomography (CT).

Study Design

Cross‐sectional study of temporal bone histopathology and radiology.

Setting

Academic medical center.

Subjects and Methods

In total, 1579 temporal bone specimens and 100 CT of the temporal bones (200 ears) were examined for JBA and any associated dehiscence of inner ear structures. Temporal bone specimens were examined for histological consequences of inner ear erosion. Jugular bulb dimensions were measured on axial CT scans and compared across groups. Accompanying demographic and clinical information were reviewed.

Results

High jugular bulbs were noted in 8.2% (130/1579) of temporal bone specimens and in 8.5% (17/200) of temporal bone CT. The prevalence of JBA increases during the first 4 decades of life and stabilizes thereafter. High‐riding jugular bulbs eroded inner ear structures such as the vestibular aqueduct, vertical facial nerve, or posterior semicircular canal in 2.8% (44/1579) of cases histologically and 1.5% (3/200) radiologically. In most, jugular bulb–mediated inner ear dehiscence was clinically and radiologically silent.

Conclusion

Jugular bulb abnormalities are common. They are present in 10% to 15% individuals and are primarily acquired by the fourth decade of life. In 1% to 3% of cases, the HRJB erodes into the inner ear and most frequently involves the vestibular aqueduct.
Vitamin D3 Deficiency Increases Sinus Mucosa Dendritic Cells in Pediatric Chronic Rhinosinusitis with Nasal Polyps
Authors: Mulligan Jennifer K. , White David R. , Wang Eric W. , Sansoni S. Ritter , Moses Helen , Yawn Robert J. , Wagner Carol , Casey Sarah E. , Mulligan Ryan M. , Schlosser Rodney J.
Published: May 2012

Objective

Dendritic cells are professional antigen presenting cells, capable of initiating Th1 or Th2 responses, and have been implicated in the pathogenesis of a number of diseases, including sinusitis. Vitamin D3 is a steroid hormone that acts on dendritic cells in a manner similar to corticosteroids. Investigators examined whether children with allergic fungal rhinosinusitis (AFRS) or chronic rhinosinusitis with nasal polyposis (CRSwNP) were vitamin D3 deficient and the relationship of vitamin D3 deficiency to dendritic cell infiltrate in the sinus mucosa.

Setting

Tertiary care university hospital.

Study Design

Retrospective, controlled study using samples collected from pediatric patients seen from August 2009 to July 2011.

Subjects and Methods

Plasma levels of 25‐hydroxy vitamin D3 were measured by enzyme‐linked immunosorbent assay in children (≤18 years old) with AFRS, CRSwNP, or CRS without nasal polyposis (CRSsNP) and in controls undergoing surgery for adenotonsillar hypertrophy. Vitamin D3 levels were confirmed using clinical diagnostic methods for those with CRSwNP or AFRS. Tissue samples were immunohistochemically stained for the dendritic cell marker CD209 and the costimulatory molecules CD80 and CD86.

Results

There was no difference in mean vitamin D3 levels between control and CRSsNP, whereas mean CRSwNP and AFRS levels were both well below the minimum recommended level of 30 ng/mL and significantly lower than control and CRSsNP levels. CD209+ dendritic cells inversely correlated with vitamin D3 but not costimulatory molecule expression.

Conclusions

These studies identify that children with CRSwNP or AFRS are vitamin D3 deficient, which may be linked to increased dendritic cell infiltrate. These results suggest a role for vitamin D3 as a key player in the immunopathology of pediatric CRSwNP.
Global civil society as shepherd: Global sexualities and the limits of solidarity from a distance
Authors: Seckinelgin Hakan
Published: May 2012

This paper critically argues that in the debates on international sexuality rights, global civil society actors assume leadership to represent the voices of those who are seen as marginalized or voiceless due to diverse injustices. This process, however, itself creates a layer of power relations within civil society which in turn leads to an under-representation of the voices and demands of people who don’t appear in the global register of sexuality politics. The paper unpacks the nature of global civil society actors’ claim to represent others and the implications of these claims for those who are being represented. The particular focus here is the ongoing debates on the position of sexual minorities in Africa with special reference to Uganda and Malawi. An analytical framework is also developed to understand the underlying mechanisms of global civil society advocacy. This is done by considering Michel Foucault’s work on pastoral power and Gayatri C. Spivak’s work on post-colonialism.
Enhancing genre-based measures of music preference by user-defined liking and social tags
Authors: Ferrer Rafael , Eerola Tuomas , Vuoskoski Jonna K.
Published: May 2012

Musical preferences are typically determined by asking participants to indicate their favourite musical genres. These genre-based measures have some considerable pitfalls, since specific pieces of music in a genre might be liked more than the genre itself, and finding consensus to define a genre is often a challenging task. The aims of the present study were to (1) assess how effective genre-based measures are at identifying musical preferences, by comparing them to free responses; (2) demonstrate how the fit can be improved between the genre-based measures and sampled population; and (3) suggest and evaluate methods that use lists of liked and disliked artists to define musical preferences. Two surveys ( n = 346 and n = 861) were administered to a university population. Both surveys contained modified versions of the STOMP (Short Test On Musical Preferences, Rentfrow & Gosling, 2003), together with open questions about music that was liked and disliked. We found that for 29% of the individuals, the genre-based measures did not successfully account for their musical preferences. A number of improvements are suggested to optimize the measures. Additionally, we introduce the Artist-based Musical Preferences (AMP) as a more ecologically valid instrument to assess musical preferences.
From Neoliberalism to Social Justice
Authors: Kaboub Fadhel
Published: May 2012

The educated unemployed youth of Tunisia have played a crucial role in the 2010 uprisings that have sparked revolutions across the entire Arab world (and beyond). It has been argued that the recent economic situation in Tunisia is the culmination of three decades of neoliberal economic policies that have contributed to the rise in income inequality, the lack of upward mobility for educated youth, and the removal of social safety nets for the working class. This paper argues that the economic success of post-Ben Ali Tunisia must do away with neoliberal economic policies and focus instead on direct job creation through public sector spending. A six-year full employment program is proposed for Tunisia in the Post Keynesian Institutionalist tradition of Hyman Minsky. The main purpose of this paper is to address the technical question of financial affordability of direct job creation, rather than focusing on the logistical aspects of the program. The paper demonstates that this program can create full employment, contribute an additional 4.8 percentage points to GDP growth, and cost 3.36 percent of GDP.

JEL Codes: B5, E12, E24, F41, 023, O38, O47, O53