bluuebunny/crossref_metadata_2025 huggingface dataset:
The Human Stratum Corneum Prevents Small Gold Nanoparticle Penetration and Their Potential Toxic Metabolic Consequences
Authors: Liu David C. , Raphael Anthony P. , Sundh Daniel , Grice Jeffrey E. , Peter Soyer H. , Roberts Michael S. , Prow Tarl W.
Published: June 2012

Nanoparticles are being used in multiple applications, ranging from biomedical and skin care products (e.g., sunscreen) through to industrial manufacturing processes (e.g., water purification). The increase in exposure has led to multiple reports on nanoparticle penetration and toxicity. However, the correlation between nanoparticle size and its penetration without physical/chemical enhancers through the skin is poorly understood—with studies instead focusing primarily on skin penetration under disrupted conditions. In this paper, we investigate the penetration and metabolic effects of 10 nm, 30 nm, and 60 nm gold nanoparticles within viable excised human skin after 24‐hour exposure using multiphoton tomograph‐fluorescence lifetime imaging microscopy. After 24 hour treatment with the 10, 30, and 60 nm gold nanoparticles, there was no significant penetration detected below the stratum corneum. Furthermore, there were no changes in metabolic output (total NAD(P)H) in the viable epidermis posttreatment correlating with lack of penetration of nanoparticles. These results are significant for estimating topical nanoparticle exposure in humans where other model systems may overestimate the exposure of nanoparticles to the viable epidermis. Our data shows that viable human skin resists permeation of small nanoparticles in a size range that has been reported to penetrate deeply in other skin models.
Interaction ofSchistosoma mansoniSporocysts and Hemocytes ofBiomphalaria
Authors: Negrão-Corrêa D. , Mattos A. C. A. , Pereira C. A. J. , Martins-Souza R. L. , Coelho P. M. Z.
Published: June 2012

Human infection bySchistosoma mansoniaffects more than 100 million people worldwide, most often in populations of developing countries of Africa, Asia, and Latin America. The transmission ofS. mansoniin human populations depends on the presence of some species ofBiomphalariathat act as an intermediate host. The compatibility betweenS. mansoniand its intermediate host is influenced by behavioral, physiological, and genetical factors of the mollusc and the parasite. The susceptibility level of the mollusc has been attributed to the capacity of internal defense system (IDS)—hemocytes and soluble components of the hemolymph—to recognize and destroy the parasite, and this will be the center of interest of this paper. The schistosome-resistantBiomphalariacan be an alternative strategy for the control of schistosomiasis.
The Triglyceride to HDL Ratio and Its Relationship to Insulin Resistance in Pre- and Postpubertal Children: Observation from the Wausau SCHOOL Project
Authors: Olson Karen , Hendricks Bryan , Murdock David K.
Published: June 2012

Insulin resistance (IR) is a risk factor for ischemic heart disease and diabetes and raises the triglyceride/high-density lipoprotein (TG/HDL) ratio in adults, but is not well defined in children. Purpose. To investigate the TG/HDL ratios in children as an IR marker. Methods. Wausau SCHOOL Project assessed 99 prepubertal and 118 postpubertal children. The TG/HDL ratio was correlated with numerous risk factors. Results. TG/HDL ratio was significantly correlated with QUICKI, HOMA-IR, zBMI, waist-to hip ratio, systolic and diastolic BP, LDL size and LDL number. A group of 32 IR children (HOMA-IR > 1 SD from the mean, i.e., >2.45) had significantly higher TG/HDL (3.11 ± 1.77) compared to non-IR children (1.86 ± 0.75). A TG/HDL ratio of ≥2.0 identified 32 of the 40 children deemed IR by HOMA-IR (>2.45) with a sensitivity of 0.80 and a specificity of 0.66. Children with TG/HDL ratio ≥3 were heavier and had higher BP, glucose, HOMA-IR, LDL number, and lower HDL level, QUICKI, and LDL size, regardless of pubertal status. Conclusion. The TG/HDL ratio is strongly associated with IR in children, and with higher BMI, waist hip ratio, BP, and more athrogenic lipid profile.
Two-Stage Fault Diagnosis Method Based on the Extension Theory for PV Power Systems
Authors: Wang Meng-Hui , Chen Mu-Jia
Published: June 2012

In order to shorten the maintenance time and make sure of the photovoltaic (PV) power generation system steadily in operation, a fault diagnosis system for photovoltaic power generation system was proposed in this paper. First, a PSIM software is used to simulate a 2.2 kW PV system, it can take the operating date of the PV system under different sunlight intensity and temperature conditions. In this paper, a two-stage diagnosis system based on the extension theory for PV power systems is proposed; the proposed method is not only be able to troubleshoot the system fault but also the damaged module can also be located. The primary strategy is to utilize the diagnosis array of daylight identification and to use light scanning of the damage array at night. Via wireless network the data is transmitted back to the diagnosis system for identifying the location of damaged module. The time and energy of manually locating the fault module can be greatly saved. Finally, the methods as proposed in this paper have been compared with other existing methods, by which to verify its superiority and usability.
Chemical Methods to Induce Beta-Cell Proliferation
Authors: Vetere Amedeo , Wagner Bridget K.
Published: June 2012

Pancreatic beta-cell regeneration, for example, by inducing proliferation, remains an important goal in developing effective treatments for diabetes. However, beta cells have mainly been considered quiescent. This “static” view has recently been challenged by observations of relevant physiological conditions in which metabolic stress is compensated by an increase in beta-cell mass. Understanding the molecular mechanisms underlining these process could open the possibility of developing novel small molecules to increase beta-cell mass. Several cellular cell-cycle and signaling proteins provide attractive targets for high throughput screening, and recent advances in cell culture have enabled phenotypic screening for small molecule-induced beta-cell proliferation. We present here an overview of the current trends involving small-molecule approaches to induce beta-cell regeneration by proliferation.
Characteristics of Wave Reflection for Vertical and Slit Caissons with Porous Structures
Authors: Jung Tae-Hwa , Lee Sung-Jae , Cho Yong-Sik
Published: June 2012

Offshore structures are occasionally located at a relatively deep water region, the outside of breakwater. In this case, these structures may be damaged by the supposition of incident and reflected waves from a vertical breakwater. To prevent the damage, the reflected waves are controlled by installing porous structures at the face of the vertical breakwater. In this study, numerical experiments are carried out to identify the characteristics of wave reflection from the porous structures installing in front of a vertical or slit caisson.
Bone-Derived IGF Mediates Crosstalk between Bone and Breast Cancer Cells in Bony Metastases
Authors: Hiraga Toru , Myoui Akira , Hashimoto Nobuyuki , Sasaki Akira , Hata Kenji , Morita Yoshihiro , Yoshikawa Hideki , Rosen Clifford J. , Mundy Gregory R. , Yoneda Toshiyuki
Published: June 2012

The continuous release of bone-stored growth factors after bone resorption promotes the colonization of circulating cancer cells. However, the precise role of each of the various growth factors remains unclear. In this study, we investigated the role of bone-derived insulin-like growth factor (IGF) in the development of bone metastases in an animal model of breast cancer. We found that local stimulation of calvarial bone resorption before cell inoculation stimulated subsequent bone metastases to that site in vivo, although inhibition of bone resorption inhibited bone metastases. Anchorage-independent growth of cancer cells was stimulated by the culture supernatants from resorbed bones, which contained elevated levels of IGF-I. This stimulation was blocked by IGF type I receptor (IGF-IR) neutralizing antibody, but not antibody targeting other bone-stored growth factors including TGF-β, fibroblast growth factors, and platelet-derived growth factors. Although recombinant human IGF-I caused IGF-IR tyrosine autophosphorylation, followed by activation of Akt and NF-κB in cancer cells, dominant-negative inhibition of IGF-IR, Akt, or NF-κB significantly reduced bone metastases with increased apoptosis and decreased mitosis in metastatic cells. Together, our findings suggest that bone-derived IGF-I bridges the crosstalk between bone and metastasized cancer cells via activation of the IGF-IR/Akt/NF-κB pathway. Disruption of this pathway therefore may represent a promising therapeutic intervention for bone metastasis. Cancer Res; 72(16); 4238–49. ©2012 AACR.
Differences in Cognitive Profile between TIA, Stroke and Elderly Memory Research Subjects: A Comparison of the MMSE and MoCA
Authors: Pendlebury S.T. , Markwick A. , de Jager C.A. , Zamboni G. , Wilcock G.K. , Rothwell P.M.
Published: June 2012

Background: The Montreal Cognitive Assessment (MoCA) appears more sensitive to mild cognitive impairment (MCI) than the Mini-Mental State Examination (MMSE): over 50% of TIA and stroke patients with an MMSE score of ≥27 (‘normal’ cognitive function) at ≥6 months after index event, score <26 on the MoCA, a cutoff which has good sensitivity and specificity for MCI in this population. We hypothesized that sensitivity of the MoCA to MCI might in part be due to detection of different patterns of cognitive domain impairment. We therefore compared performance on the MMSE and MoCA in subjects without major cognitive impairment (MMSE score of ≥24) with differing clinical characteristics: a TIA and stroke cohort in which frontal/executive deficits were expected to be prevalent and a memory research cohort. Methods: The MMSE and MoCA were done on consecutive patients with TIA or stroke in a population-based study (Oxford Vascular Study) 6 months or more after the index event and on consecutive subjects enrolled in a memory research cohort (the Oxford Project to Investigate Memory and Ageing). Patients with moderate-to-severe cognitive impairment (MMSE score of <24), dysphasia or inability to use the dominant arm were excluded. Results: Of 207 stroke patients (mean age ± SD: 72 ± 11.5 years, 54% male), 156 TIA patients (mean age 71 ± 12.1 years, 53% male) and 107 memory research subjects (mean age 76 ± 6.6 years, 46% male), stroke patients had the lowest mean ± SD cognitive scores (MMSE score of 27.7 ± 1.84 and MoCA score of 22.9 ± 3.6), whereas TIA (MMSE score of 28.4 ± 1.7 and MoCA score of 24.9 ± 3.3) and memory subject scores (MMSE score of 28.5 ± 1.7 and MoCA score of 25.5 ± 3.0) were more similar. Rates of MoCA score of <26 in subjects with normal MMSE ( ≥27) were lowest in memory subjects, intermediate in TIA and highest after stroke (34 vs. 48 vs. 67%, p < 0.001). The cerebrovascular patients scored lower than the memory subjects on all MoCA frontal/executive subtests with differences being most marked in visuoexecutive function, verbal fluency and sustained attention (all p < 0.0001) and in stroke versus TIA (after adjustment for age and education). Stroke patients performed worse than TIA patients only on MMSE orientation in contrast to 6/10 subtests of the MoCA. Results were similar after restricting analyses to those with an MMSE score of ≥27. Conclusions: The MoCA demonstrated more differences in cognitive profile between TIA, stroke and memory research subjects without major cognitive impairment than the MMSE. The MoCA showed between-group differences even in those with normal MMSE and would thus appear to be a useful brief tool to assess cognition in those with MCI, particularly where the ceiling effect of the MMSE is problematic.
Heart healthy diet and risk of myocardial infarction and venous thromboembolism
Authors: Enga Kristin F. , Njølstad Inger , Hansen John-Bjarne , Braekkan Sigrid K. , Hansen-Krone Ida J.
Published: June 2012

Prudent dietary patterns are associated with reduced risk of arterial cardiovascular diseases (CVD). Limited data exist on the relation between diet and venous thromboembolism (VTE). The aim of our prospective, population based study was to investigate the association of a heart healthy diet on risk of myocardial infarction (MI) and VTE. Information on dietary habits was available in 18,062 subjects, aged 25–69, who participated in the fourth Tromsø study, 1994–1995. Dietary patterns were assessed by a slightly modified version of the validated SmartDiet score; a 13-item questionnaire producing a diet score based on the intakes of fat, fibre, fruit and vegetables. Incident events of MI (n=518) and VTE (n=172) were recorded to the end of follow-up December 31, 2005 (median follow-up 10.8 years). Cox-regression models were used to calculate hazard ratios (HR). A healthy diet score of >27 points (upper tertile) was associated with 17% reduced risk of MI (HR: 0.83, 95% confidence interval [CI]: 0.66–1.06), and no association with VTE (HR: 1.01; 95%CI: 0.66–1.56), compared to <24 points (lower tertile) in multivariable analysis. High intake of fish, fruit, vegetables and polyunsatured fat had a 23% reduced risk of MI (HR 0.77; 95%CI: 0.60–0.98), but no association with VTE (HR 0.95; 95%CI: 0.64–1.40). A heart healthy diet showed an even more favourable association with MI in obese subjects (HR: 0.62; 95%CI: 0.41–0.95), but not with VTE. Our findings suggest that a heart healthy dietary pattern is associated with moderately reduced risk of MI, but not related to risk of VTE.
Evidence that fibrinolytic changes in paediatric obesity translate into a hypofibrinolytic state
Authors: Semeraro Fabrizio , Giordano Paola , Faienza Maria F. , Cavallo Luciano , Semeraro Nicola , Colucci Mario
Published: June 2012

Paediatric obesity, like adulthood obesity, is associated with an increase of fibrinolysis inhibitors. No study, however, has evaluated the impact of these changes on plasma fibrinolytic capacity. We investigated plasma fibrinolysis and the role therein of the fibrinolytic changes associated with obesity in 59 obese children (body mass index > 95th percentile) and 40 matched controls. Fibrinolysis was investigated by measuring 1) the plasma levels of relevant fibrinolytic factors; 2) the in vitro fibrinolytic capacity under different conditions, using a microplate plasma clot lysis assay; 3) the circulating levels of markers of clotting and fibrinolysis activation. Plasminogen activator inhibitor 1 (PAI-1), total thrombin activatable fibrinolysis inhibitor (TAFI) and fibrinogen levels were higher in obese children as compared to controls (p<0.01). Plasma clots from obese children lysed significantly slower than control clots when exposed to exogenous plasminogen activator, indicating a greater resistance to fibrinolysis. By the use of a selective inhibitor of activated TAFI and by regression analyses we found that fibrinolysis resistance in obese samples was attributable to PAI-1 increase and to enhanced TAFI activation. The ratio between the circulating levels of D-dimer and thrombin-antithrombin complex, a marker of in vivo fibri-nolysis, was significantly lower in obese children, suggesting a reduced fibrinolytic efficiency. These data indicate that paediatric obesity is associated with a hypofibrinolytic state which might contribute to the increased thrombotic risk associated with this condition.
The anti-von Willebrand factor aptamer ARC1779 increases von Willebrand factor levels and platelet counts in patients with type 2B von Willebrand disease
Authors: Jilma-Stohlawetz Petra , Knöbl Paul , Gilbert James C. , Jilma Bernd
Published: June 2012

Blockade of hyperactive von Willebrand factor (VWF) by ARC1779 blunted the platelet drop induced by desmopressin in patients with type 2B von Willebrand disease (VWD). Thus, we hypothesised that ARC1779 may increase VWF levels and correct thrombocytopenia. Three thrombocytopenic patients suffering from type 2B VWD received a loading dose of 0.23 mg/kg ARC1779 followed by 4 μg/kg/min intravenously for 72 hours in a prospective clinical trial. ARC1779 was well tolerated and safe. Plasma concentrations of ARC1779 increased to 76 μg/ml (59–130) leading to an immediate decrease of free VWF A1 domains. VWF/FVIII levels increased as early as 12 h after start of infusion, peaked near the end of infusion, and returned to baseline at follow-up. VWF ristocetin cofactor activity (VWF:RCo) showed a median 10-fold increase 8 hours after end of infusion, while the median VWF-antigen and FVIII increase was less (5-fold and 4-fold, respectively). Most importantly inhibition of hyperactive VWF rapidly increased platelet counts from 40x109/l (38–58 x109/l) to a maximum of 146 x109/l (107–248 x109/l). In conclusion, ARC1779 markedly increases VWF/FVIII levels and most importantly improves or even corrects thrombocytopenia in VWD type 2B patients. This underscores the in vivo potency of ARC1779.
NT-pro-BNP levels in patients with acute pulmonary embolism are correlated to right but not left ventricular volume and function
Authors: Klok Frederikus A. , van der Bijl Noortje , de Roos Albert , Kroft Lucia J. M. , Huisman Menno V. , Pasha Sharif M.
Published: June 2012

N-terminal pro-Brain Natriuretic Peptide (NT-pro-BNP) is primarily secreted by left ventricular (LV) stretch and wall tension. Notably, NT-pro-BNP is a prognostic marker in acute pulmonary embolism (PE), which primarily stresses the right ventricle (RV). We sought to evaluate the relative contribution of the RV to NT-pro-BNP levels during PE. A posthoc analysis of an observational prospective outcome study in 113 consecutive patients with computed tomography (CT)-proven PE and 226 patients in whom PE was clinically suspected but ruled out by CT. In all patients RV and LV function was established by assessing ECG-triggered-CT measured ventricular end-diastolic-volumes and ejection fraction (EF). NT-pro-BNP was assessed in all patients. The correlation between RV and LV end-diastolic-volumes and systolic function was evaluated by multiple linear regression corrected for known con-founders. In the PE cohort increased RVEF (β-coefficient (95% confidence interval [CI]) –0.044 (± –0.011); p<0.001) and higher RV enddiastolic-volume (β-coefficient 0.005 (± 0.001); p<0.001) were significantly correlated to NT-pro-BNP, while no correlation was found with LVEF ( β-coefficient 0.005 (± 0.010); p=0.587) and LV end-diastolic-volume (β-coefficient –0.003 (± 0.002); p=0.074). In control patients without PE we found a strong correlation between NT-pro-BNP levels and LVEF ( β-coefficient –0.027 (± –0.006); p<0.001) although not LV enddiastolic-volume (β-coefficient 0.001 (± 0.001); p=0.418). RVEF (β-co-efficient –0.002 (± –0.006); p=0.802) and RV end-diastolic-volume (β-coefficient <0.001 (± 0.001); p=0.730) were not correlated in patients without PE. In PE patients, lower RVEF and higher RV end-diastolic-volume were significantly correlated to NT-pro-BNP levels as compared to control patients without PE. These observations provide patho-physiological ground for the well-known prognostic value of NT-pro-BNP in acute PE.
Red blood cell distribution width is associated with poor clinical outcome in acute cerebral infarction
Authors: Kim Jinkwon , Kim Young , Song Tae-Jin , Park Ji , Lee Hye , Nam Chung , Nam Hyo , Heo Ji
Published: June 2012

Increased red blood cell distribution width (RDW), which is a marker of anisocytosis, is associated with mortality and cardiovascular events in the general population and in patients with heart failure or coronary heart disease. We investigated whether RDW in acute cerebral infarction is predictive of functional outcome and mortality. A total of 847 consecutive patients with first-ever acute cerebral infarction who presented to the emergency department within seven days of symptom onset were enrolled in this study. We investigated the association of RDW with poor functional outcome (modified Rankin Scale >2) and all-cause mortality at three months, as well as survival time for one year after stroke onset. Multivariate logistic regression revealed that higher RDW was independently associated with poor functional outcome (adjusted odds ratio [OR], 1.222 per 1% increment in RDW, 95% confidence interval [CI] 1.059–1.409, p=0.006) and all-cause death (adjusted OR, 1.395 per 1% increment in RDW, 95% CI 1.168–1.665, p<0.001) at three months after stroke onset. RDW was an independent predictor of survival in multivariate Cox-proportional regression model (adjusted hazard ratio, 1.328 per 1% increment in RDW, 95%CI 1.178–1.498, p<0.001). The addition of RDW to a survival model significantly increased predictability for survival across the entire follow-up period (weighted average of the area-under the curves, 0.858 vs. 0.841, p<0.05). In conclusion, higher RDW measured in cases of acute stage cerebral infarction was associated with poor functional outcome and mortality. RDW may be used as a biomarker for the prediction of long-term outcomes in patients with acute cerebral infarction.
Long-Term Survival and Recurrence After Acute Myocardial Infarction in England, 2004 to 2010
Authors: Smolina Kate , Wright F. Lucy , Rayner Mike , Goldacre Michael J.
Published: June 2012

Background—

There are limited population-based national data on prognosis in survivors of acute myocardial infarction (AMI), particularly on long-term survival and the risk of recurrence.

Methods and Results—

Record linkage of hospital and mortality data identified 387 452 individuals in England who were admitted to hospital with a main diagnosis of AMI between 2004 and 2010 and who survived for at least 30 days. Seven years after an AMI, the risk of death from any cause in survivors of first or recurrent AMI was, respectively, 2 and 3 times higher than that in the English general population of equivalent age. For all survivors of a first AMI, the risk of a second AMI was highest during the first year and the cumulative risk increased more gradually thereafter. For men, 1- and 7-year cumulative risks were 5.6% (95% confidence interval [CI], 5.5–5.7) and 13.9% (95% CI, 13.7–14.1); for women, they were 7.2% (95% CI, 7.1–7.4) and 16.2% (95% CI, 16.0–16.5). Older age, higher deprivation, no revascularization procedures, and presence of comorbidities were associated with higher recurrence risk.

Conclusions—

Survivors of both first and recurrent AMI remained at a significantly higher risk of death compared with the general population for at least 7 years after the event. For survivors of first AMI, the influence of predisposing factors for second AMI lessened with time after the initial event. The results reinforce the importance of acute clinical care and secondary prevention in improving long-term prognosis of hospitalized AMI patients.
Clinical Evidence, Practice Guidelines, and β-Blocker Utilization Before Major Noncardiac Surgery
Authors: Wijeysundera Duminda N. , Mamdani Muhammad , Laupacis Andreas , Fleisher Lee A. , Beattie W. Scott , Johnson Sindhu R. , Kolstad Jonathan , Neuman Mark D.
Published: June 2012

Background—

Largely on the basis of 2 randomized trials published in the 1990s, β-blockers were initially promoted as an evidence-based intervention for preventing cardiac complications of noncardiac surgery. However, subsequent studies raised concerns about a widespread use of perioperative β-blockade. Little is known regarding how this changing evidence influenced the use of perioperative β-blockers in clinical practice.

Methods and Results—

We conducted a population-based, time-series analysis (April 1999 to March 2010) among residents of Ontario, Canada (age 66 years and older), to evaluate the influence of research publications and practice guidelines on rates of new β-blocker prescriptions before major elective noncardiac surgery. In an analysis of 249 828 procedures, the rate of new β-blocker prescriptions increased from 26.3 per 1000 procedures in April 1999 to 62.7 per 1000 procedures in the first quarter of 2005, after which it decreased to 19.7 per 1000 procedures by March 2010. We observed a marked decrease in prescriptions (
P
=0.004) during early 2005, without any preceding publications that raised concerns about perioperative β-blockade. There was no change (
P
=0.98) in prescription rates after the May 2008 publication of a multicenter, randomized trial that showed increased mortality from perioperative β-blockade. Prescribing trends remain unchanged after revisions of related practice guidelines in 2002 (
P
=0.28) and 2006 (
P
=0.53).

Conclusions—

After a period characterized by increasing adoption of preoperative β-blockade between 1999 and 2005, prescriptions rates subsequently fell from 2005 to 2010. Further research is needed to understand the basis for these changes, which are only partially explained by evidence of potential harm.
Genetically Induced Moderate Inhibition of the Proteasome in Cardiomyocytes Exacerbates Myocardial Ischemia-Reperfusion Injury in Mice
Authors: Tian Zongwen , Zheng Hanqiao , Li Jie , Li Yifan , Su Huabo , Wang Xuejun
Published: June 2012

Rationale:

Both cardiomyocyte-restricted proteasome functional enhancement and pharmacological proteasome inhibition (PSMI) were shown to attenuate myocardial ischemia/reperfusion (I/R) injury. The role of cardiac proteasome dysfunction during I/R and the perspective to diminish I/R injury by manipulating proteasome function remain unclear.

Objectives:

We sought to determine proteasome adequacy in I/R hearts, create a mouse model of cardiomyocyte-restricted PSMI (CR-PSMI), and test CR-PSMI impact on I/R injury.

Methods and Results:

Myocardial I/R were modeled by ligation (30 minutes) and subsequent release of the left anterior descending artery in mice overexpressing GFPdgn, a validated surrogate proteasome substrate. At 24 hours of reperfusion, myocardial proteasome activities were significantly lower whereas total ubiquitin conjugates and GFPdgn protein levels were markedly higher in all regions of the I/R hearts than the sham controls, indicative of proteasome functional insufficiency. CR-PSMI in intact mice was achieved by transgenic (tg) overexpression of a peptidase-disabled mouse β5 subunit (T60A-β5) driven by an attenuated mouse mhc6 promoter. Overexpressed T60A-β5 can replace endogenous β5 and inhibits proteasome chymotrypsin-like activities in the heart. Mice with moderate CR-PSMI showed no abnormalities at the baseline but displayed markedly more pronounced structural and functional damage during I/R, compared with non-tg littermates. The exacerbation of I/R injury by moderate CR-PSMI was associated with significant increases in the protein level of PTEN and protein kinase Cδ (PKCδ), decreased Akt activation, and reduced PKCɛ.

Conclusions:

Myocardial I/R causes proteasome functional insufficiency in cardiomyocytes and moderate CR-PSMI augments PTEN and PKCδ, suppresses Akt and PKCɛ, increases cardiomyocyte apoptosis, and aggravates I/R injury in mice.
Antenatal Factors Associated With Perinatal Arterial Ischemic Stroke
Authors: Darmency-Stamboul Véronique , Chantegret Corinne , Ferdynus Cyril , Mejean Nathalie , Durand Christine , Sagot Paul , Giroud Maurice , Bejot Yannick , Gouyon Jean Bernard
Published: June 2012

Background and Purpose—

Perinatal arterial ischemic stroke (PAIS) is a common cause of hemiplegic cerebral palsy in children. The diagnosis of PAIS is based on cerebral imaging. The objective of our study was to determine prenatal risk factors associated with PAIS.

Methods—

A retrospective case–control study was nested in the whole population of Burgundy, France, from January 2000 to December 2007. Case patients were confirmed by review of brain imaging and medical records. Three control subjects per case were randomly selected from the study population by sex, term, place, and year of birth.

Results—

PAIS was confirmed in 32 patients and its incidence was one per 4400 live births. In comparison to control subjects, clinical conditions significantly associated to cases were gestational diabetes (16.1% versus 4.2%;
P
=0.04), fetal heart rate abnormalities (35.5% versus 10.9%;
P
=0.001), and meconium-stained liquor (40% versus 12%;
P
<0.001). At the limit of statistical significance were found maternal smoking before (39.3% versus 22.9%;
P
=0.08) and during pregnancy (32.1% versus 16.7%;
P
=0.07), cord abnormalities (29% versus 14.1%;
P
=0.06), and cesarean delivery (28.1% versus 14.6%;
P
=0.08). In the multivariate analysis, maternal smoking during pregnancy (OR, 3.1; 95% CI, 1.1–8.8;
P
=0.04) was the only risk factor significantly associated with PAIS.

Conclusions—

This study is the first to identify maternal smoking during pregnancy as an independent prenatal risk factor of PAIS. Additional prospective studies are needed to confirm this result and to investigate the role of maternal smoking in fetal and neonatal thrombogenesis.
Telmisartan on Top of Antihypertensive Treatment Does Not Prevent Progression of Cerebral White Matter Lesions in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) MRI Substudy
Authors: Weber Ralph , Weimar Christian , Blatchford Jon , Hermansson Karin , Wanke Isabel , Möller-Hartmann Claudia , Gizewski Elke R. , Forsting Michael , Demchuk Andrew M. , Sacco Ralph L. , Saver Jeffrey L. , Warach Steven , Diener Hans-Christoph , Diehl Anke ,   for the PRoFESS Imaging Substudy Group
Published: June 2012

Background and Purpose—

High blood pressure is one of the main risk factors for cerebral white matter lesions (WMLs). There is limited evidence from one randomized trial that blood pressure-lowering is able to slow WML progression. We investigated whether telmisartan prevents WML progression in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial.

Methods—

This predefined substudy comprised 771 patients (mean age, 65 years) with recent ischemic stroke of noncardioembolic origin who received telmisartan or placebo during a mean follow-up of 27.9 (SD, 7.6) months and had 2 evaluable MRI examinations after index stroke and at study closeout. All MRI scans were centrally adjudicated for progression of periventricular and subcortical WML by 2 neuroradiologists blinded to treatment allocation.

Results—

Mean blood pressure was 3.0/1.3 mm Hg lower with telmisartan compared with placebo at follow-up MRI. There was no statistically significant difference in progression of the mean periventricular WML score (least squares mean difference, 0.14; 95% CI, −0.12 to 0.39;
P
=0.29) and mean subcortical WML diameter (least squares mean difference, −0.35 mm; 95% CI, −1.00 to 0.31 mm;
P
=0.30) during follow-up between patients on telmisartan and placebo.

Conclusions—

Treatment with telmisartan on top of existing antihypertensive medication did not result in significant blood pressure-lowering and did not prevent the progression of WML in patients with a recent ischemic stroke in this patient cohort. Our analysis is limited by the relatively short follow-up period.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique Identifier: NCT00153062.
Clinical Supervision in South Korea and the United States
Authors: Son Eunjung , Ellis Michael V. , Yoo Sung-Kyung
Published: June 2012

To provide cross-cultural empirical data for the advancement of supervisor competencies, we investigated differences in clinical supervision between South Korean and the United States from the supervisees’ perspective. Specifically, the comparative descriptive study had 191 South Korean and 187 U.S. supervisee participants receiving clinical supervision. Pursuing a hypothesis testing approach, comparative descriptive data across several variables suggested that there were more similarities than differences between supervision practices between the two cultures. Implications for theory, research, and practice were discussed.
Control strategy design and experimental research on a four-shaft electronic continuously variable transmission hybrid electric vehicle
Authors: Yu Hai-Sheng , Zhang Jian-Wu , Zhang Tong
Published: June 2012

A new electromechanical power-splitting full-hybrid transmission with two shifting elements, namely a four-shaft planetary gear and an electronic continuously variable transmission, is introduced in this paper. This transmission was developed with the aim of combining all the advantages of an internal combustion engine and two electric motors in an optimal way so as to improve the power performance and the fuel economy. The architecture and analogy of the four-shaft planetary gear are analysed, a control strategy is designed, and the engine management system and hybrid control system are calibrated. To evaluate the performance, the control strategy and the calibrated results, nine tests were performed as per the New European Driving Cycle under various initial conditions, different maps and different thresholds. The test results indicate that a four-shaft planetary gear, electronic continuously variable transmission hybrid electric vehicle can realize good fuel economy and good emissions performance except for nitrogen oxide emissions. The best fuel consumption obtained was 5.4 l/100 km. The amount of nitrogen oxide emissions needs to be decreased by optimizing the control strategy of the hybrid control system and calibration of the engine management system in future research.
Pyrrolidinium sulfate and ammonium sulfate ionic liquids as lubricant additives for steel/steel contact lubrication
Authors: Pejaković V , Kronberger M , Mahrova M , Vilas M , Tojo E , Kalin M
Published: June 2012

In this work, we report on the BuMepyr-MeSO4 and Et3MeN-MeSO4 ionic liquids that were synthesized and used as additives in a glycerol model lubricant for steel/steel contacts. Tests were performed with three different ionic liquid concentrations, i.e. 0.625 wt%, 2.5 wt% and 8 wt%, as well as in glycerol without any ionic liquid (neat glycerol) and in neat ionic liquids (100%) at 100 °C. The wear and friction were measured and the worn surfaces were examined with scanning electron microscopy and atomic force microscopy. The results show a reduction of the wear and friction with the use of ionic liquids as additives, when compared to the neat glycerol. With an increasing ionic-liquid concentration in the glycerol, the friction was observed to decrease and the wear to increase. In this work, however, the results obtained for neat ionic liquids represent the lowest values in terms of both friction and wear.
Ethnic federalism and its potential to dismember the Ethiopian state
Authors: Mehretu Assefa
Published: June 2012

The Horn of Africa has become the most fragmented post-colonial region in Africa. The largest state in the region, Ethiopia, with its unequalled demographic and resource power lost one of its provinces to secession and the rest of the country became divided into ethnic enclosures called killiloch, which are federal states with tribal designation. The recitation of divisive counter-narratives on the history of the Ethiopian state by ethnically inspired governing and non-governing political elite has minimized the collective identity of Ethiopians leading to their decomposition into tribal groupings in killiloch with neo-tribal restrictive covenants that include the right of secession. The supporters of such divisions have touted the policies as emancipatory that are ostensibly designed to help in the self-determination of Ethiopia’s various nationalities and to govern their own local affairs under a form of dual federalism (exclusive states’ rights). The objective of this article is to reflect on the adverse consequences of dual federalism based on ethnic killils and to explore an alternative framework for cultural and functional integration of the Ethiopian state under the rubric of cooperative federalism.
Organizational culture and public sector reforms in a post–Washington consensus era: Lessons from Ghana’s good reformers
Authors: Owusu Francis Y.
Published: June 2012

Reforming Africa’s public sector has been on the agenda of African governments and their development partners for decades and yet the problem persists. This failure can be attributed to two related factors: solutions to the ‘African public sector problem’ have been dictated by external interests, and the policies have ignored the experiences of organizations within those countries. This article contributes to the search for effective reform policies by making the case for inclusion of the experiences of organizations within each country. Using the concept of organizational culture as a framework, I propose an approach based on the following claims: In every country there are some public organizations that perform relatively well, given their constraints; there is the need to understand why and how there are poor and good performing organizations within the same country; and information from such analysis should form the basis of public sector reform policies. The applicability of the approach is demonstrated with a study of Ghana.
Examining a Therapeutic Yoga Program for Prostate Cancer Survivors
Authors: Ross Zahavich Ashley N. , Robinson John A. , Paskevich David , Culos-Reed S. Nicole
Published: June 2012

Background. In the earlier stages of prostate cancer, effective treatments have created a need for research to focus on practices that may improve quality of life throughout survivorship. Physical activity is a significant supportive care management strategy for prostate cancer survivors, though the optimal modality is not yet understood. Hypotheses. The authors hypothesized that yoga would be a feasible physical activity option for prostate cancer survivors and their support persons and that the incorporation of social support would increase physical activity adherence. Methods. This 14-week feasibility study involved a 7-week class-based yoga program (adherence phase), followed by 7 weeks of self-selected physical activity (maintenance phase). Demographic information, physical activity behavior, quality of life, fatigue, stress, mood, and fitness variables were assessed at 3 time points. Prostate cancer survivors’ perceived social support was rated during yoga and after yoga. Results. Class attendance was 6.1 and 5.8 for prostate cancer survivors (n = 15) and their support persons (n = 10), respectively, for the 7 classes. Levels of perceived social support were higher for those who brought a support person. Significant improvements with regard to stress, fatigue, and mood before and after yoga class (all Ps < .05) were reported by all participants. No clinically significant changes were noted on prostate cancer survivor’s quality of life or fatigue over the course of the 14-week study. Conclusions. Yoga is a feasible physical activity option for prostate cancer survivors. The program had a promising uptake rate, high program adherence rate, and there were acute program benefits with regard to stress, fatigue, and mood for all participants. Future examination is warranted with regard to chronic benefits and group cohesion influences on levels of perceived social support.
BCR/ABL and chromosomal instability: debate resolved
Authors: Carroll Martin
Published: June 2012

In this issue of Blood, Chakraborty and colleagues provide conclusive proof that primary chronic myeloid leukemia (CML) cells from patients in chronic phase demonstrate chromosomal instability after DNA damage, suggesting that BCR/ABL, among its myriad described functions, dysregulates nonhomologous end joining (NHEJ) starting the progression of cells toward CML blast crisis.1
Quaternary structures of recombinant, cellular, and serum forms of Thymidine Kinase 1 from dogs and humans
Authors: Hanan Sharif , Jagarlamudi Kiran Kumar , Liya Wang , Ellen He , Staffan Eriksson
Published: June 2012

Background

Thymidine kinase 1 (TK1) is a salvage enzyme involved in DNA precursor synthesis, and its expression is proliferation dependent. A serum form of TK1 has been used as a biomarker in human medicine for many years and more recently to monitor canine lymphoma. Canine TK1 has not been cloned and studied. Therefore, dog and human TK1 cDNA were cloned and expressed, and the recombinant enzymes characterized. The serum and cellular forms of canine and human TK1 were studied by size-exclusion chromatography and the level of TK1 protein was determined using polyclonal and monoclonal anti-TK1 antibodies.

Results

Canine TK1 phosphorylated the thymidine (dThd) analog 3'-azido-thymidine (AZT) as efficiently as it did dThd, whereas AZT phosphorylation by human TK1 was less efficient than that of dThd. Dog TK1 was also more thermostable and pH tolerant than the human enzyme. Oligomeric forms were observed with both enzymes in addition to the tetrameric and dimeric forms. Cellular TK1 was predominantly seen in dimeric and tetrameric forms, in the case of both dog TK1 from MDCK cells and human TK1 from CEM cells. Active serum TK1 was found mainly in a high molecular weight form, and treatment with a reducing agent shifted the high molecular weight complex to lower molecular weight forms with reduced total activity. Western blot analysis demonstrated a polypeptide of 26 kDa (dog) and 25 kDa (human) for cellular and serum TK1. There was no direct correlation between serum TK1 activity and protein level. It appears that a substantial fraction of serum TK1 is not enzymatically active.

Conclusions

These results suggest that the serum TK1 protein differs from cellular or recombinant forms, is more active in high molecular weight complexes, and is sensitive to reducing agents. The results presented here provide important information for the future development and use of serum TK1 as a diagnostic biomarker in human and veterinary medicine.
Molecular evolution of dihydrouridine synthases
Authors: Kasprzak Joanna M , Czerwoniec Anna , Bujnicki Janusz M
Published: June 2012

Background

Dihydrouridine (D) is a modified base found in conserved positions in the D-loop of tRNA in Bacteria, Eukaryota, and some Archaea. Despite the abundant occurrence of D, little is known about its biochemical roles in mediating tRNA function. It is assumed that D may destabilize the structure of tRNA and thus enhance its conformational flexibility. D is generated post-transcriptionally by the reduction of the 5,6-double bond of a uridine residue in RNA transcripts. The reaction is carried out by dihydrouridine synthases (DUS). DUS constitute a conserved family of enzymes encoded by the orthologous gene family COG0042. In protein sequence databases, members of COG0042 are typically annotated as “predicted TIM-barrel enzymes, possibly dehydrogenases, nifR3 family”.

Results

To elucidate sequence-structure-function relationships in the DUS family, a comprehensive bioinformatic analysis was carried out. We performed extensive database searches to identify all members of the currently known DUS family, followed by clustering analysis to subdivide it into subfamilies of closely related sequences. We analyzed phylogenetic distributions of all members of the DUS family and inferred the evolutionary tree, which suggested a scenario for the evolutionary origin of dihydrouridine-forming enzymes. For a human representative of the DUS family, the hDus2 protein suggested as a potential drug target in cancer, we generated a homology model. While this article was under review, a crystal structure of a DUS representative has been published, giving us an opportunity to validate the model.

Conclusions

We compared sequences and phylogenetic distributions of all members of the DUS family and inferred the phylogenetic tree, which provides a framework to study the functional differences among these proteins and suggests a scenario for the evolutionary origin of dihydrouridine formation. Our evolutionary and structural classification of the DUS family provides a background to study functional differences among these proteins that will guide experimental analyses.
Bayesian models for comparative analysis integrating phylogenetic uncertainty
Authors: Villemereuil Pierre de , Wells Jessie A , Edwards Robert D , Blomberg Simon P
Published: June 2012

Background

Uncertainty in comparative analyses can come from at least two sources: a) phylogenetic uncertainty in the tree topology or branch lengths, and b) uncertainty due to intraspecific variation in trait values, either due to measurement error or natural individual variation. Most phylogenetic comparative methods do not account for such uncertainties. Not accounting for these sources of uncertainty leads to false perceptions of precision (confidence intervals will be too narrow) and inflated significance in hypothesis testing (e.g. p-values will be too small). Although there is some application-specific software for fitting Bayesian models accounting for phylogenetic error, more general and flexible software is desirable.

Methods

We developed models to directly incorporate phylogenetic uncertainty into a range of analyses that biologists commonly perform, using a Bayesian framework and Markov Chain Monte Carlo analyses.

Results

We demonstrate applications in linear regression, quantification of phylogenetic signal, and measurement error models. Phylogenetic uncertainty was incorporated by applying a prior distribution for the phylogeny, where this distribution consisted of the posterior tree sets from Bayesian phylogenetic tree estimation programs. The models were analysed using simulated data sets, and applied to a real data set on plant traits, from rainforest plant species in Northern Australia. Analyses were performed using the free and open source software OpenBUGS and JAGS.

Conclusions

Incorporating phylogenetic uncertainty through an empirical prior distribution of trees leads to more precise estimation of regression model parameters than using a single consensus tree and enables a more realistic estimation of confidence intervals. In addition, models incorporating measurement errors and/or individual variation, in one or both variables, are easily formulated in the Bayesian framework. We show that BUGS is a useful, flexible general purpose tool for phylogenetic comparative analyses, particularly for modelling in the face of phylogenetic uncertainty and accounting for measurement error or individual variation in explanatory variables. Code for all models is provided in the BUGS model description language.