bluuebunny/crossref_metadata_2025 huggingface dataset:
A Randomized Controlled Trial of Auricular Transcutaneous Electrical Nerve Stimulation for Managing Posthysterectomy Pain
Authors: Tsang Hin Cheung , Lam Chi Shan , Chu Ping Wing , Yap Jacqueline , Fung Tak Yuen , Cheing Gladys L. Y.
Published: June 2011

Background. A patient‐ and assessor‐blinded randomized controlled trial was conducted to examine the effectiveness of auricular transcutaneous electrical nerve stimulation (TENS) in relieving posthysterectomy pain.
Method. Forty‐eight women who had undergone a total abdominal hysterectomy were randomly assigned into three groups (n = 16 each) to receive either (i) auricular TENS to therapeutic points (the true TENS group), (ii) auricular TENS to inappropriate points (the sham TENS group), or (iii) 20 minutes of bed rest with no stimulation (the control group). The intervention was delivered about 24 hours after the operation. A visual analogue scale was used to assess pain while resting (VAS‐rest) and upon huffing (VAS‐huff) and coughing (VAS‐cough), and the peak expiratory flow rate (PEFR) was assessed before and at 0, 15, and 30 minutes after the intervention.
Result. As compared to the baseline, only the true TENS group reported a significant reduction in VAS‐rest (P = .001), VAS‐huff (P = .004), and VAS‐cough (P = .001), while no significant reduction in any of the VAS scores was seen in the sham TENS group (all P > .05). In contrast, a small rising trend was observed in the VAS‐rest and VAS‐huff scores of the control group, while the VAS‐cough score remained largely unchanged during the period of the study. A between‐group comparison revealed that all three VAS scores of the true TENS group were significantly lower than those of the control group at 15 and 30 minutes after the intervention (all P < .02). No significant between‐group difference was observed in PEFR at any point in time. Conclusion. A single session of auricular TENS applied at specific therapeutic points significantly reduced resting (VAS‐rest) and movement‐evoked pain (VAS‐huff, VAS‐cough), and the effects lasted for at least 30 minutes after the stimulation. The analgesic effects of auricular TENS appeared to be point specific and could not be attributed to the placebo effect alone. However, auricular TENS did not produce any significant improvement in the performance of PEFR.
Damage of Splenic T Lymphocyte Proliferation and Differentiation and Its Normalization by Electroacupuncture in Morphine‐Dependent Mice Mode
Authors: Li Hong-Yu , Zhang Rong , Cui Cai-Lian , Han Ji-Sheng , Wu Liu-Zhen
Published: June 2011

In a previous paper we reported that electroacupuncture (EA) could suppress opioid withdrawal syndrome and increase the appetite, sleep, and body weight in heroin addicts or morphine dependent animals. Considering that opioids were known to inhibit immune function, the present study was designed to observe whether EA could modulate the immune status of morphine dependent and withdrawal mice. We found that chronic morphine‐induced decrease of splenic T lymphocyte proliferation and IL‐2 production can be significantly raised by 2 Hz EA, and the fluctuation of CD4+/CD8+ ratio was also run to the baseline level by the EA. These findings indicated that chronic morphine exposure‐induced immune dysfunction in mice could be normalized by 2 Hz EA.
Excretory-Secretory Products from Hookworm L3and Adult Worms Suppress Proinflammatory Cytokines in Infected Individuals
Authors: Geiger Stefan Michael , Fujiwara Ricardo Toshio , Freitas Paula Albuquerque , Massara Cristiano Lara , Carvalho Omar dos Santos , Corrêa-Oliveira Rodrigo , Bethony Jeffrey Michael
Published: June 2011

We compared the effects of larval and adult worm excretory-secretory (ES) products from hookworm on the proliferative responses and cytokine secretion in peripheral blood mononuclear cells (PBMCs) from hookwormpatients and egg-negative, nonendemic controls. When compared with negative controls, mitogen-stimulated PBMC from hookworm-infected individuals showed a significantly reduced proliferative response when adult worm ES antigen was added to the cultures. Furthermore, in hookworm-infected individuals a significant downmodulation of inflammatory interleukin (IL)-6 and tumor necrosis factor (TNF)-αsecretion resulted when PBMCs were stimulated with mitogen in combination with larval or adult worm ES. Both, interferon (IFN)-γand IL-10 secretion were significantly lower in stimulated PBMC from infected individuals; however the IFN-γ/IL-10 ratio was much lower in hookworm-infected patients. Comparable effects, although at lower concentrations, were achieved when PBMCs from both groups were incubated with living hookworm third-stage larvae. We suggest that hookworm ES products downmodulate proliferative responses and inflammation during the chronic phase of the disease and facilitate early larval survival or adult worm persistence in the gut.
Mesenchymal Stem Cell Therapy Modulates the Inflammatory Response in Experimental Traumatic Brain Injury
Authors: Galindo Layla T. , Filippo Thais R. M. , Semedo Patricia , Ariza Carolina B. , Moreira Caroline M. , Camara Niels O. S. , Porcionatto Marimelia A.
Published: June 2011

Therapy with mesenchymal stem cells (MSCs) has showed to be promising due to its immunomodulatory function. Traumatic brain injury (TBI) triggers immune response and release of inflammatory mediators, mainly cytokines, by glial cells creating a hostile microenvironment for endogenous neural stem cells (NSCs). We investigated the effects of factors secreted by MSCs on NSCin vitroand analyzed cytokines expressionin vitroin a TBI model. Ourin vitroresults show that MSC-secreted factors increase NSC proliferation and induce higher expression of GFAP, indicating a tendency toward differentiation into astrocytes.In vivoexperiments showed that MSC injection at an acute model of brain injury diminishes a broad profile of cytokines in the tissue, suggesting that MSC-secreted factors may modulate the inflammation at the injury site, which may be of interest to the development of a favorable microenvironment for endogenous NSC and consequently to repair the injured tissue.
Light Sensor Platform Based on the Integration of Bacteriorhodopsin with a Single Electron Transistor
Authors: Walczak Karl A. , Bergstrom Paul L. , Friedrich Craig R.
Published: June 2011

This paper reports on the integration of an optical protein with single electron transistors to form a nano-bio-hybrid device for sensing. Bacteriorhodopsin (bR) is an optoelectric protein that translocates a proton across a distance of several nanometers in response to an absorbed photon of incident light. This charge gradient results in a measurable voltage in the dried state. Single electron transistors (SETs) have active regions consisting of one or more quantum islands with a size typically 10 nanometers or less. Integrating bacteriorhodopsin with the gate of a SET provides a device capable of a modulated electrical output in response to optical modulation at the device gate. Modulation of the optoelectric activity of the bR by chemical binding with a targeted environmental antigen can form a direct chemical-to-electrical sensor reducing the size and complexity of fluorescence-based systems. The work resulted in electrical resistance and capacitance characterization of purple membrane containing bR under variable illumination to ensure minimal impact on SET operation. Purple membrane containing bacteriorhodopsin was electrodeposited on the SET gates, and current throughput was well correlated with variable and cyclic illumination. It was confirmed that bR optoelectric activity is capable of driving SETs.
Frequency of Positive Surgical Margin at Prostatectomy and Its Effect on Patient Outcome
Authors: Iczkowski Kenneth A. , Lucia M. Scott
Published: June 2011

A positive surgical margin at prostatectomy is defined as tumor cells touching the inked edge of the specimen. This finding is reported in 8.8% to 42% of cases (median about 20%) in various studies. It is one of the main determinants of eventual biochemical (PSA) failure, generally associated with a doubled or tripled risk of failure. The effect of a positive margin on outcome can be modified by stage or grade and the length, number and location of positive margins, as well as by technical operative approach and duration of operator experience. This paper tabulates data from the past decade of studies on margin status.
Burning Rate in Impinging Jet Flames
Authors: Lipatnikov A. N.
Published: June 2011

A method for evaluating burning velocity in premixed turbulent flames stabilized in divergent
mean flows is quantitatively validated using numerical approximations of measured
axial profiles of the mean combustion progress variable, mean and conditioned axial velocities,
and axial turbulent scalar flux, obtained by four research groups from seven different
flames each stabilized in an impinging jet. The method is further substantiated by
analyzing the combustion progress variable balance equation that is yielded by the extended
Zimont model of premixed turbulent combustion. The consistency of the model
with the aforementioned experimental data is also demonstrated.
No Evidence of XMRV or MuLV Sequences in Prostate Cancer, Diffuse Large B-Cell Lymphoma, or the UK Blood Donor Population
Authors: Robinson Mark James , Tuke Philip William , Erlwein Otto , Tettmar Kate I. , Kaye Steve , Naresh Kikkeri N. , Patel Anup , Walker Marjorie M. , Kimura Takahiro , Gopalakrishnan Ganesh , Tedder Richard S. , McClure Myra O.
Published: June 2011

Xenotropic murine leukaemia virus-related virus (XMRV) is a recently described retrovirus which has been claimed to infect humans and cause associated pathology. Initially identified in the US in patients with prostate cancer and subsequently in patients with chronic fatigue syndrome, doubt now exists that XMRV is a human pathogen. We studied the prevalence of genetic sequences of XMRV and related MuLV sequences in human prostate cancer, from B cell lymphoma patients and from UK blood donors. Nucleic acid was extracted from fresh prostate tissue biopsies, formalin-fixed paraffin-embedded (FFPE) prostate tissue and FFPE B-cell lymphoma. The presence of XMRV-specific LTR or MuLV genericgag-like sequences was investigated by nested PCR. To control for mouse DNA contamination, a PCR that detected intracisternal A-type particle (IAP) sequences was included. In addition, DNA and RNA were extracted from whole blood taken from UK blood donors and screened for XMRV sequences by real-time PCR. XMRV or MuLV-like sequences were not amplified from tissue samples. Occasionally MuLVgagand XMRV-LTR sequences were amplified from Indian prostate cancer samples, but were always detected in conjunction with contaminating murine genomic DNA. We found no evidence of XMRV or MuLV infection in the UK blood donors.
MEMS-Based Endoscopic Optical Coherence Tomography
Authors: Sun Jingjing , Xie Huikai
Published: June 2011

Early cancer detection has been playing an important role in reducing cancer mortality. Optical coherence tomography (OCT), due to its micron-scale resolution, has the ability to detect cancerous tissues at their early stages. For internal organs, endoscopic probes are needed as the penetration depth of OCT is about 1–3 mm. MEMS technology has the advantages of fast speed, small size, and low cost, and it has been widely used as the scanning engine in endoscopic OCT probes. Research results have shown great potential for OCT in endoscopic imaging by incorporating MEMS scanning mirrors. Various MEMS-OCT designs are introduced, and their imaging results are reviewed in the paper.
Population Change and Its Driving Factors in Rural, Suburban, and Urban Areas of Wisconsin, USA, 1970–2000
Authors: Chi Guangqing , Ventura Stephen J.
Published: June 2011

Population growth (or decline) is influenced by many factors that fall into the broad realms of demographic characteristics, socioeconomic conditions, transportation infrastructure, natural amenities, and land use and development across space and time. This paper adopts an integrated spatial regression approach to investigate the spatial and temporal variations of these factors′ effects on population change. Specifically, we conduct the analysis at the minor civil division level in Wisconsin, USA, from 1970 to 2000. The results suggest that the factors have varying effects on population change over time and across rural, suburban, and urban areas. Their effects depend upon the general trend of population redistribution processes, local dynamics, and areal characteristics. Overall, a systematic examination of population change should consider a variety of factors, temporal and spatial variation of their effects, and spatial spillover effects. The examination should have the flexibility to identify and incorporate influential factors at a given point in time and space, not to adhere to a single set of drivers in all circumstances. The findings have important implications for population predictions used for local and regional planning.
Gene Therapy: A Potential Approach for Cancer Pain
Authors: Handy Chalonda R. , Krudy Christina , Boulis Nicholas
Published: June 2011

Chronic pain is experienced by as many as of cancer patients at some point during the disease. This pain can be directly cancer related or arise from a sensory neuropathy related to chemotherapy. Major pharmacological agents used to treat cancer pain often lack anatomical specificity and can have off-target effects that create new sources of suffering. These concerns establish a need for improved cancer pain management. Gene therapy is emerging as an exciting prospect. This paper discusses the potential for viral vector-based treatment of cancer pain. It describes studies involving vector delivery of transgenes to laboratory pain models to modulate the nociceptive cascade. It also discusses clinical investigations aimed at regulating pain in cancer patients. Considering the prevalence of pain among cancer patients and the growing potential of gene therapy, these studies could set the stage for a new class of medicines that selectively disrupt nociceptive signaling with limited off-target effects.
Modeling the QSAR of ACE-Inhibitory Peptides with ANN and Its Applied Illustration
Authors: He Ronghai , Ma Haile , Zhao Weirui , Qu Wenjuan , Zhao Jiewen , Luo Lin , Zhu Wenxue
Published: June 2011

A quantitative structure-activity relationship (QSAR) model of angiotensin-converting enzyme- (ACE-) inhibitory peptides was built with an artificial neural network (ANN) approach based on structural or activity data of 58 dipeptides (including peptide activity, hydrophilic amino acids content, three-dimensional shape, size, and electrical parameters), the overall correlation coefficient of the predicted versus actual data points is , and the model was applied in ACE-inhibitory peptides preparation from defatted wheat germ protein (DWGP). According to the QSAR model, the C-terminal of the peptide was found to have principal importance on ACE-inhibitory activity, that is, if the C-terminal is hydrophobic amino acid, the peptide's ACE-inhibitory activity will be high, and proteins which contain abundant hydrophobic amino acids are suitable to produce ACE-inhibitory peptides. According to the model, DWGP is a good protein material to produce ACE-inhibitory peptides because it contains 42.84% of hydrophobic amino acids, and structural information analysis from the QSAR model showed that proteases of Alcalase and Neutrase were suitable candidates for ACE-inhibitory peptides preparation from DWGP. Considering higher DH and similar ACE-inhibitory activity of hydrolysate compared with Neutrase, Alcalase was finally selected through experimental study.
Photocatalytic Degradation of Phenolics by N-Doped Mesoporous Titania under Solar Radiation
Authors: Mangrulkar Priti A. , Kamble Sanjay P. , Joshi Meenal M. , Meshram Jyotsna S. , Labhsetwar Nitin K. , Rayalu Sadhana S.
Published: June 2011

In this study, nitrogen-doped mesoporous titania was synthesized by templating method using chitosan. This biopolymer chitosan plays the dual role of acting as a template (which imparts mesoporosity) and precursor for nitrogen. BET-SA, XRD, UV-DRS, SEM, and FTIR were used to characterize the photocatalyst. The doping of nitrogen into TiO2lattice and its state was substantiated and measured by XPS. The photocatalytic activity of the prepared N-doped mesoporous titania for phenol ando-chlorophenol degradation was investigated under solar and artificial radiation. The rate of photocatalytic degradation was observed to be higher foro-chlorophenol than that of phenol. The photodegradation ofo-chlorophenol was 98.62% and 72.2%, while in case of phenol, degradation to the tune of 69.25% and 30.58% was achieved in solar and artificial radiation. The effect of various operating parameters, namely, catalyst loading, pH, initial concentration and the effect of coexisting ions on the rate of photocatalytic degradation were studied in detail.
Melanoma Prognosis: A REMARK-Based Systematic Review and Bioinformatic Analysis of Immunohistochemical and Gene Microarray Studies
Authors: Schramm Sarah-Jane , Mann Graham J.
Published: June 2011

Despite intensive research efforts, within-stage survival rates for melanoma vary widely. Pursuit of molecular biomarkers with improved prognostic significance over clinicohistological measures has produced extensive literature. Reviews have synthesized these data, but none have systematically partitioned high-quality studies from the remainder across different molecular methods nor examined system properties of that output. Databases were searched for studies analyzing protein expression by immunohistochemistry (n = 617, extending the only systematic review to date by 102 studies) or for gene expression microarray studies (n = 45) in melanoma in relation to outcome. REMARK-derived criteria were applied to identify high-quality studies. Biomarkers and pathways were functionally assessed by using gene ontology software. Most manuscripts did not meet REMARK-based criteria, an ongoing trend that can impede translational research. Across REMARK-compliant literature, 41 proteins were significantly associated with outcome. Multimarker tests consistently emerged among the most promising potential biomarkers, indicating a need to continue assessing candidates in that composite setting. Twenty-one canonical pathways were populated by outcome-related proteins but not by those that failed to show such an association; we propose that this set of pathways warrants closer investigation to understand drivers of poor outcome in melanoma. Two-gene expression microarray studies met REMARK-based criteria reflecting a genuine paucity of literature in the area. The 254 outcome-related genes were examined for correspondences with the systematically identified protein signature. This analysis highlighted proliferating cell nuclear antigen and survivin as priorities for further examination as biomarkers in melanoma prognosis, and illustrated ongoing need to integrate alternative approaches to biomarker discovery in melanoma translational research. Mol Cancer Ther; 10(8); 1520–8. ©2011 AACR.
Hepatitis C Virus Adversely Affects Quality of Life
Authors: Cillo Umberto , Amodio Piero , Ronco Claudio , Soni Sachin S. , Zanus Giacomo , Minazzato Lina , Salari Annalisa , Neri Daniele , Bombonato Giancarlo , Schiff Sami , Bianco Tonino
Published: June 2011

Background: Chronic liver disease secondary to hepatitis C virus (HCV) infection is a common clinical problem. HCV is likely to adversely affect the quality of life (QoL) of the patient. This effect is said to be disproportionate to the severity of the disease. The aim of our study was to evaluate QoL in HCV-positive patients focusing both on health status and subjective satisfaction. Methods: Twenty-four patients with combined HCV and alcoholic liver disease (ETOH-HCV) were enrolled in the study. We adopted two generic tools: SF-36 (a health status questionnaire) and SAT-P (a satisfaction profile) for psychological assessment of the patients. SF-36 and SAT-P scores of ETOH-HCV patients were compared with scores of 23 patients with alcoholic liver disease (ETOH). The scores obtained from the study groups were also compared with the reference scores of the healthy Italian population. Results: Both the groups were comparable with respect to age, histological and clinical severity of liver disease (as assessed by MELD and Child Pugh scores). Patients with ETOH-HCV scored less in the vitality and role emotional status domains of the SF-36 scores and the psychological function, social function and free time domains of the satisfaction profile. Conclusions: These results show a significant impact of HCV infection on health status and subjective satisfaction.
A Heparin-Coated Dialysis Filter (AN69 ST) Does Not Reduce Clotting during Hemodialysis when Compared to a Conventional Polysulfone Filter (F×8)
Authors: Sagedal Solbjørg , Witczak Bartlomiej J. , Osnes Kåre , Hartmann Anders , Os Ingrid , Eikvar Lars , Klingenberg Olav , Brosstad Frank
Published: June 2011

Background: We investigated whether the heparin-coated AN69 ST hemodialysis (HD) filter induced less hypercoagulability during HD than a conventional polysulfone filter (F×8). Methods: In a crossover design, 11 patients were treated alternately with AN69 ST and F×8 filters (45 sessions). All filters were primed with unfractionated heparin (UFH) and unadsorbed UFH was removed by saline flushing. Half the conventional dalteparin dose was given as a bolus dose at the start of HD. Clotting was evaluated hourly in the venous air trap. Prothrombin fragments 1 and 2 (PF1 + 2), antithrombin (AT), β-TG and anti-FXa activity were repeatedly measured. Results: One patient treated with enalapril had two repeated adverse reactions to the AN69 ST filter and was excluded from the study. Use of the AN69 ST filter did not decrease the mean clot score or PF1 + 2, but decreased β-TG compared to the F×8 filter. Conclusion: The heparin-coated AN69 ST filter did not induce less coagulation when compared to the F×8 filter.
TEM Stereometric Analyses of Glomeruli in Aging OVE26 Transgenic Diabetic Mice
Authors: Teiken Jennifer M. , Epstein Paul N. , Carlson Edward C.
Published: June 2011

Background/Aims: Glomerular lesions in diabetic nephropathy (DN) have been studied in numerous murine diabetic models, but the critical feature of aging is often absent. Since histopathology indicates that in mice, DN glomerular lesions may just begin to develop at about 5 months of age, we utilized the long-lived OVE26 transgenic diabetic model for stereometric analyses of DN glomerulopathic aging. Methods: Albuminuria was determined by ELISA, and transmission electron microscopy stereometry was utilized exclusively to demonstrate changes in glomerular cell density and number, and alterations in the glomerular filtration barrier in OVE26 mice at 60, 150, and 450 days of age. Results: Compared to age-matched controls, albuminuria in diabetic mice is significant at 60 days. At 150 days, glomerular volume and mesangial, endothelial and total cell numbers, and podocyte effacement are significantly increased, while podocyte, endothelial, and total cell density are significantly decreased. Endothelial fenestrations are decreased, and glomerular basement membrane thickness is increased. At 450 days, stereometric alterations are exacerbated. Conclusion: Our data indicate that in OVE26 mice, albuminuria precedes morphological glomerular lesions and could be due to early-onset hyperglycemia. Moreover, in this model, most DN glomerulopathic lesions occur relatively late in life, and it is possible that they may result from prolonged hyperglycemia-induced oxidative stress.
Cilostazol Improves Outcome after Subarachnoid Hemorrhage: A Preliminary Report
Authors: Suzuki Satoshi , Sayama Tetsuro , Nakamura Takaharu , Nishimura Hiroyuki , Ohta Masaru , Inoue Takuya , Mannoji Hiromichi , Takeshita Iwao
Published: June 2011

Background: Cerebral vasospasm (VS) is the most common cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). Reversal of VS by intra-arterial infusion of cyclic adenosine monophosphate (cAMP)-elevating agents has been reported; however, the preventive role in the development of VS is not fully understood. This study is designed to evaluate the possible efficacy of using cilostazol, a selective inhibitor of phosphodiesterase type 3 and a cAMP-elevating agent, in patients with SAH. Methods: In this prospective randomized study, we enrolled 100 SAH patients who met the following criteria: neck clipping within 72 h after onset, Hunt and Hess (HH) score ≤4, modified Rankin scale (mRS) score ≤2 prior to ictus, and no serious cardiovascular complications. Patients were divided into control and cilostazol groups; we focused on the effects of cilostazol on the decrease in the incidence of symptomatic VS, cerebral infarction, and the mRS score at discharge. Result: Patients’ age, male/female ratio, mRS score prior to ictus, HH grade, Fisher group, site of the aneurysm, drugs prescribed during the observation period, and length of hospital stay were not different between the groups. Cilostazol did not significantly decrease the incidence of symptomatic VS (37.3% in the control vs. 22.4% in the cilostazol group, p = 0.183) and cerebral infarction (27.5% in control vs. 10.2% in the cilostazol, p = 0.091). However, mRS score was significantly improved at discharge (2.6 in controls vs. 1.5 in the cilostazol group, p = 0.041). Patients’ age being ≤65 years (OR = 8.47, 95% CI = 2.45–29.32, p = 0.0007), Fisher group ≤3 (OR = 4.64, 95% CI = 1.00–21.45, p = 0.049), HH grade ≤2 (OR = 4.31, 95% CI = 1.27–14.59, p = 0.019), no hydrocephalus (OR = 8.55, 95% CI = 1.72–19.23, p = 0.0046), and cilostazol use (OR = 5.52, 95% CI = 1.61–18.90, p = 0.0065) were independent predictors of good outcomes (mRS score ≤2). Conclusion: Cilostazol may improve outcomes after SAH, but further double-blind, placebo-controlled studies are required for a definitive conclusion.
Quantitating Glomerular Endothelial Fenestration: An Unbiased Stereological Approach
Authors: Najafian Behzad , Mauer Michael
Published: June 2011

Background/Aims: Glomerular endothelial cells are fenestrated, allowing for especially high transcellular hydraulic conductivity. Current knowledge about endothelial fenestration structural changes in disease conditions is limited, partly due to the absence of robust methodologies to quantitate these structures. Herein, we propose a novel method for estimating the percentage of endothelial fenestration. Methods: An unbiased stereological method based on contiguity of two phases and surface area density estimation using isotropic uniform random line probes was developed. A line grid for intercept counting and classifying endothelial coverage of fenestrated versus non-fenestrated areas was designed. The method was applied to renal biopsies from 15 patients with Fabry disease and 9 normal living kidney donor controls. Results: The percentage of glomerular capillary endothelial coverage which was fenestrated was lower in Fabry patients (43 ± 12%) versus controls (53 ± 9%; p = 0.047). The fraction of endothelial surface which was fenestrated was greater on the peripheral versus mesangial zones of the capillary walls in both Fabry patients (p = 0.00002) and controls (p = 0.0005). Conclusion: The proposed method provides an unbiased tool to quantitate endothelial fenestration changes in glomeruli. The practical example introduced showed reduced glomerular endothelial fenestration in Fabry nephropathy.
Perinatal Asphyxia in a Nonhuman Primate Model
Authors: Jacobson Misbe Elizabeth N. , Richards Todd L. , McPherson Ronald J. , Burbacher Thomas M. , Juul Sandra E.
Published: June 2011

Perinatal asphyxia is a leading cause of brain injury in neonates, occurring in 2–4 per 1,000 live births, and there are limited treatment options. Because of their similarity to humans, nonhuman primates are ideal for performing preclinical tests of safety and efficacy for neurotherapeutic interventions. We previously developed a primate model of acute perinatal asphyxia using 12–15 min of umbilical cord occlusion. Continuing this research, we have increased cord occlusion time from 15 to 18 min and extended neurodevelopmental follow-up to 9 months. The purpose of this report is to evaluate the increase in morbidity associated with 18 min of asphyxia by comparing indices obtained from colony controls, nonasphyxiated controls and asphyxiated animals. Pigtail macaques were delivered by hysterotomy after 0, 15 or 18 min of cord occlusion, then resuscitated. Over the ensuing 9 months, for each biochemical and physiologic parameters, behavioral and developmental evaluations, and structural and spectroscopic MRI were recorded. At birth, all asphyxiated animals required resuscitation with positive pressure ventilation and exhibited biochemical and clinical characteristics diagnostic of hypoxic-ischemic encephalopathy, including metabolic acidosis and attenuated brain activity. Compared with controls, asphyxiated animals developed long-term physical and cognitive deficits. This preliminary report characterizes the acute and chronic consequences of perinatal asphyxia in a nonhuman primate model, and describes diagnostic imaging tools for quantifying correlates of neonatal brain injury as well as neurodevelopmental tests for evaluating early motor and cognitive outcomes.
Iron Chelation with Deferasirox in Two Patients with HFE Hemochromatosis and Chronic Anemia
Authors: Nagler M. , Gregor M. , Wuillemin W.A.
Published: June 2011

We present 2 patients with hyperferritinemia, increased liver iron and hemochromatosis-associated HFE genotypes. At diagnosis, both patients had chronic anemia that prevented initiation of phlebotomy. Iron chelation with deferasirox proved to be a safe and effective means of substantially lowering ferritin levels.
Outcome after Thrombolysis for Acute Isolated Posterior Cerebral Artery Occlusion
Authors: Meier Niklaus , Fischer Urs , Schroth Gerhard , Findling Oliver , Brekenfeld Caspar , El-Koussy Marwan , De Marchis Gian Marco , Mono Marie-Luise , Jung Simon , Gralla Jan , Nedeltchev Krassen , Mattle Heinrich P. , Arnold Marcel
Published: June 2011

Background: To date, there is limited data on intra-arterial thrombolysis (IAT) and intravenous thrombolysis (IVT) for isolated posterior cerebral artery (PCA) occlusion. We aimed to evaluate recanalization, outcome and quality of life in patients who undergo thrombolysis for isolated PCA occlusion. Methods: Analysis of 9 patients treated with IAT and 9 patients treated with IVT with short-term (3 months) outcome and long-term (median 23 months) outcome after IAT. Results: 9 of 546 patients treated with IAT (4 women and 5 men; median age 66 years) had isolated PCA occlusion. Median baseline National Institute of Health Stroke Scale (NIHSS) score on admission was 9. Eight patients presented with visual field defects and variable additional symptoms. One patient suffered bithalamic infarction. Median time to treatment was 5.8 h. Recanalization was complete in 2, partial in 2, minimal in 2, and not achieved in 3 patients. Recanalization tended to be better when the microcatheter was placed in or close to the thrombus. We observed no major complications, and 3 months outcome was favorable (modified Rankin Scale score 0–2) in 67% of the patients after IAT. During the same period, 9 patients with PCA occlusion were treated with IVT with 89% favorable clinical outcomes at 3 months. At long-term follow-up after IAT, neuropsychological domains were more severely impaired than other neurologic functions. Conclusion: IAT is a feasible treatment of isolated PCA strokes. Clinical outcome was favorable in the majority of patients after IAT and IVT. No major complications were observed. Further studies are needed to compare IAT and IVT for isolated PCA stroke.
Retinal Arteriolar Tortuosity and Cardiovascular Risk Factors in a Multi-Ethnic Population Study of 10-Year-Old Children; the Child Heart and Health Study in England (CHASE)
Authors: Owen Christopher G. , Rudnicka Alicja R. , Nightingale Claire M. , Mullen Robert , Barman Sarah A. , Sattar Naveed , Cook Derek G. , Whincup Peter H.
Published: June 2011

Objective—

To examine the association between cardiovascular risk factors and retinal arteriolar tortuosity in a multi-ethnic child population.

Methods and Results—

Cross sectional study of 986 UK primary school children of South Asian, black African Caribbean, and white European origin aged 10 to 11 years. Anthropometric measurements and retinal imaging were carried out and a fasting blood sample collected. Digital images of retinal arterioles were analyzed using a validated semiautomated measure of tortuosity. Associations between tortuosity and cardiometabolic risk factors were analyzed using multi-level linear regression, adjusted for gender, age, ethnicity, arteriole branch status, month, and school. Levels of arteriolar tortuosity were similar in boys and girls and in different ethnic groups. Retinal arteriolar tortuosity was positively associated with levels of triglyceride, total and LDL cholesterol, and systolic and diastolic blood pressure. One standard deviation increases in these risk factors were associated with 3.7% (95% CI: 1.2%, 6.4%), 3.3% (0.9%, 5.8%), 3.1% (0.6%, 5.6%), 2.0% (−0.3%, 4.2%), and 2.3% (0.1%, 4.6%) increases in tortuosity, respectively. Adiposity, insulin resistance, and blood glucose showed no associations with tortuosity.

Conclusion—

Established cardiovascular risk factors, strongly linked to coronary heart disease in adulthood, may influence retinal arteriolar tortuosity at the end of the first decade of life.
Chromobox Protein Homolog 3 Is Essential for Stem Cell Differentiation to Smooth Muscles In Vitro and in Embryonic Arteriogenesis
Authors: Xiao Qingzhong , Wang Gang , Yin Xiaoke , Luo Zhenling , Margariti Andriani , Zeng Lingfang , Mayr Manuel , Ye Shu , Xu Qingbo
Published: June 2011

Objective—

Smooth muscle cell (SMC) differentiation is a critical process during cardiovascular formation and development, but the underlying molecular mechanism remains unclear.

Methods and Results—

Here we demonstrated that chromobox protein homolog 3 (Cbx3) is crucial for SMC differentiation from stem cells and that the chromodomain and chromoshadow domain of Cbx3 are responsible for Cbx3-induced SMC differentiation. Moreover, we identified that 4 amino acids (165 to 168) within the chromoshadow domain of Cbx3 are key elements for Cbx3 interaction with Dia-1- and Cbx3-induced SMC differentiation. Mechanistically, we found that Cbx3 mediates SMC differentiation through modulating serum response factor (SRF) recruitment to the promoters of SMC genes, in which the interaction between Cbx3 and Dia-1/SRF plays a crucial role in this process. Moreover, our in vivo study demonstrated that the misexpression of Cbx3 within neural crest cells of chick embryos resulted in the death of chick embryos at early stages because of the maldevelopment of branchial arch arteries.

Conclusion—

Our findings suggest that the interaction between Cbx3 and Dia-1/SRF is essential for SMC differentiation from stem cells and for the development of functional cardiovascular system.
Botulinum Toxin Injection in Epicardial Autonomic Ganglia Temporarily Suppresses Vagally Mediated Atrial Fibrillation
Authors: Oh Seil , Choi Eue-Keun , Zhang Youhua , Mazgalev Todor N.
Published: June 2011

Background—

Autonomic denervation may suppress atrial fibrillation (AF) vulnerability. This study was designed to assess the short- to mid-term effects of botulinum toxin, a cholinergic neurotransmission blocker, on AF inducibility.

Methods and Results—

A total of 23 mongrel dogs were studied. The sinus node and atrioventricular node epicardial fat pads were exposed through a right lateral thoracotomy. Botulinum toxin (Botox, 50 U per fat pad) or 0.9% normal saline (control) was injected into the center of each of the 2 fat pads. The electrophysiological effects were evaluated at 1, 2, and 3 weeks (7 to 8 animals at each time point) with and without cervical vagal stimulation. The vagal stimulation effects on the sinus and atrioventricular nodes were inhibited, and dispersion of atrial effective refractory period was lower at 1 week in the Botox group. Significant suppression of AF inducibility was observed at 1 week but disappeared at 2 and 3 weeks. These changes were not observed in the control group.

Conclusions—

Temporary suppression of vagally mediated AF, for at least 1 week, was achieved with botulinum toxin injection in this canine model. This effect might be associated with reduced dispersion of effective refractory period. A temporary autonomic block using botulinum toxin might be a novel therapeutic option for several clinical conditions such as post–cardiac surgery AF.
The Roles of Lipid Oxidation Products and Receptor Activator of Nuclear Factor-κB Signaling in Atherosclerotic Calcification
Authors: Demer Linda , Tintut Yin
Published: June 2011

This review focuses on the roles of oxylipids and receptor activator of nuclear factor-κB ligand signaling in calcific cardiovascular disease. Both intimal and valvular calcifications are closely associated with atherosclerosis, leading investigators to study the role of atherogenic oxidatively modified lipids (oxylipids). Results have identified the molecular signaling through which oxylipids induce osteogenic differentiation and calcification in vascular cells. A surprising concomitant finding was that, in bona fide osteoblasts from skeletal bone, oxylipids have the opposite effect, ie, inhibiting osteoblastic maturation. This is the basis for the lipid hypothesis of osteoporosis. Oxylipids also induce resorptive osteoclastic cells within the bone environment, raising the question of whether resorptive osteoclasts can be harnessed in the vascular context for cell-based therapy to remove artery wall mineral deposits. The challenge is that vascular cells produce antiosteoclastogenic factors, including the soluble decoy receptor for receptor activator of nuclear factor-κB ligand, possibly accounting for the paucity of resorptive cells and the dominance of mineral in atherosclerotic plaque. These factors may have therapeutic use in osteoclastogenic removal of mineral deposits from arteries.
What Is the Current Status of Invasive Treatment of Extracranial Carotid Artery Disease?
Authors: Naylor A. Ross
Published: June 2011

Year 2011 sees the publication of US guidelines that recommend expanding indications for carotid artery stenting into “average-risk” patients, whereas guidelines from Australia/New Zealand largely do not. This article reviews the status of invasive treatment of carotid disease and highlights 2 controversial issues that were not really addressed in these guidelines: (1) a lack of emphasis on the importance of intervening rapidly after transient ischemic attack/minor stroke; and (2) why continue to recommend that only “highly selected” asymptomatic patients should undergo intervention when virtually no-one pays any attention?
Subtherapeutic International Normalized Ratio in Warfarin-Treated Patients Increases the Risk for Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis
Authors: Seet Raymond C.S. , Zhang Yi , Moore S. Arthur , Wijdicks Eelco F. , Rabinstein Alejandro A.
Published: June 2011

Background and Purpose—

There is uncertainty whether warfarin-treated patients (despite international normalized ratio <1.7) have increased risks of symptomatic intracerebral hemorrhage after intravenous thrombolysis.

Methods—

Vascular risk factors, stroke subtype, and outcome measures were compared between warfarin- and nonwarfarin-treated patients undergoing acute thrombolysis within 3 hours of symptom onset.

Results—

From 212 patients (mean age, 74±14 years; 50% men) studied, 14 (6.5%) had prior warfarin use. After adjusting for age, baseline National Institutes of Health Stroke Scale, and stroke subtype, warfarin-treated patients had significantly increased risks of developing symptomatic intracerebral hemorrhage (adjusted OR, 14.7; 95% CI, 1.3 to 54.3). A trend for poorer stroke recovery and increased mortality was observed in warfarin-treated patients on univariate, but not on multivariable, analyses.

Conclusions—

Warfarin-treated patients with stroke have increased risks of symptomatic intracerebral hemorrhage after thrombolytic treatment. These data raise safety concerns of thrombolytic treatment in warfarin-treated patients with subtherapeutic international normalized ratio.
The Theoretician’s Clouds—Heavier or Lighter than Air? On Densities in Atmospheric Thermodynamics
Authors: Pelkowski Joachim , Frisius Thomas
Published: June 2011

Threefold densities may be introduced into atmospheric thermodynamics. For rainless clouds the general indirect or implicit conclusion is that they are denser than moist air under the same circumstances, although in a classic treatise a different conclusion was reached, to the effect that cloudy air (containing water and/or ice) is less dense than moist air under the same pressure and temperature. By reconsidering carefully different ways of determining densities, any doubts that may linger after reading the scant literature dealing explicitly with the density of a cloud are dispelled.
A Model of Atlantic Heat Content and Sea Level Change in Response to Thermohaline Forcing
Authors: Zhai Xiaoming , Johnson Helen L. , Marshall David P.
Published: June 2011

The response of ocean heat content in the Atlantic to variability in the meridional overturning circulation (MOC) at high latitudes is investigated using a reduced-gravity model and the Massachusetts Institute of Technology (MIT) general circulation model (MITgcm). Consistent with theoretical predictions, the zonal-mean heat content anomalies are confined to low latitudes when the high-latitude MOC changes rapidly, but extends to mid- and high latitudes when the high-latitude MOC varies on decadal or multidecadal time scales. This low-pass-filtering effect of the mid- and high latitudes on zonal-mean heat content anomalies, termed here the “Rossby buffer,” is shown to be associated with the ratio of Rossby wave basin-crossing time to the forcing period at high northern latitudes. Experiments using the MITgcm also reveal the importance of advective spreading of cold water in the deep ocean, which is absent in the reduced-gravity model. Implications for monitoring ocean heat content and sea level changes are discussed in the context of both models. It is found that observing global sea level variability and sea level rise using tide gauges can substantially overestimate the global-mean values.
Assessing the Roles of Three Eddy Types in Restratifying the Labrador Sea after Deep Convection
Authors: Gelderloos Renske , Katsman Caroline A. , Drijfhout Sybren S.
Published: June 2011

Restratification after deep convection is one of the key factors in determining the temporal variability of dense water formation in the Labrador Sea. In the subsurface, it is primarily governed by lateral buoyancy fluxes during early spring. The roles of three different eddy types in this process are assessed using an idealized model of the Labrador Sea that simulates the restratification season. The first eddy type, warm-core Irminger rings, is shed from the boundary current along the west coast of Greenland. All along the coastline, the boundary current forms boundary current eddies. The third type, convective eddies, arises directly around the convection area. In the model, the latter two eddy types are together responsible for replenishing 30% of the winter heat loss within 6 months. Irminger rings add another 45% to this number. The authors’ results thus confirm that the presence of Irminger rings is essential for a realistic amount of restratification in this area. The model results are compared to observations using theoretical estimates of restratification time scales derived for the three eddy types. The time scales are also used to explain contradicting conclusions in previous studies on their respective roles.
Robust Ensemble Filtering and Its Relation to Covariance Inflation in the Ensemble Kalman Filter
Authors: Luo Xiaodong , Hoteit Ibrahim
Published: June 2011

A robust ensemble filtering scheme based on the H∞ filtering theory is proposed. The optimal H∞ filter is derived by minimizing the supremum (or maximum) of a predefined cost function, a criterion different from the minimum variance used in the Kalman filter. By design, the H∞ filter is more robust than the Kalman filter, in the sense that the estimation error in the H∞ filter in general has a finite growth rate with respect to the uncertainties in assimilation, except for a special case that corresponds to the Kalman filter.

The original form of the H∞ filter contains global constraints in time, which may be inconvenient for sequential data assimilation problems. Therefore a variant is introduced that solves some time-local constraints instead, and hence it is called the time-local H∞ filter (TLHF). By analogy to the ensemble Kalman filter (EnKF), the concept of ensemble time-local H∞ filter (EnTLHF) is also proposed. The general form of the EnTLHF is outlined, and some of its special cases are discussed. In particular, it is shown that an EnKF with certain covariance inflation is essentially an EnTLHF. In this sense, the EnTLHF provides a general framework for conducting covariance inflation in the EnKF-based methods. Some numerical examples are used to assess the relative robustness of the TLHF–EnTLHF in comparison with the corresponding KF–EnKF method.
Observations of the Surface Boundary Structure within the 23 May 2007 Perryton, Texas, Supercell
Authors: Skinner Patrick S. , Weiss Christopher C. , Schroeder John L. , Wicker Louis J. , Biggerstaff Michael I.
Published: June 2011

In situ data collected within a weakly tornadic, high-precipitation supercell occurring on 23 May 2007 near Perryton, Texas, are presented. Data were collected using a recently developed fleet of 22 durable, rapidly deployable probes dubbed “StickNet” as well as four mobile mesonet probes. Kinematic and thermodynamic observations of boundaries within the supercell are described in tandem with an analysis of data from the Shared Mobile Atmospheric Research and Teaching Radar.

Observations within the rear-flank downdraft of the storm exhibit large deficits of both virtual potential temperature and equivalent potential temperature, with a secondary rear-flank downdraft gust front trailing the mesocyclone. A primarily thermodynamic boundary resided across the forward-flank reflectivity gradient of the supercell. This boundary is characterized by small deficits in virtual potential temperature coupled with positive perturbations of equivalent potential temperature. The opposing thermodynamic perturbations appear to be representative of modified storm inflow, with a flux of water vapor responsible for the positive perturbations of the equivalent potential temperature. Air parcels exhibiting negative perturbations of virtual potential temperature and positive perturbations of equivalent potential temperature have the ability to be a source of both baroclinically generated streamwise horizontal vorticity and greater potential buoyancy if ingested by the low-level mesocyclone.
Self, Belonging and Social Change
Authors: May Vanessa
Published: June 2011

One of the central interests of sociology is the relationship between self and society, and in particular how social change affects individuality, constraining or liberating the selves that we can be. This article proposes that because a sense of belonging plays a central role in connecting the person to the social, it can act as a window into studying the relationship between social change and the self. Furthermore, belonging offers a complex person-centred and dynamic approach that avoids reifying social structures, but rather depicts them as actively lived. A focus on belonging thus allows a dynamic examination of the mutual influence between self and society, and of how everyday practices are both regulated and creative, and hence generative of social change.