bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in Mice
Authors: Asagami Tomoko , Belanoff Joseph K. , Azuma Junya , Blasey Christine M. , Clark Robin D. , Tsao Philip S.
Published: July 2011

Previous research has shown that mifepristone can prevent and reverse weight gain in animals and human subjects taking antipsychotic medications. This proof-of-concept study tested whether a more potent and selective glucocorticoid receptor antagonist could block dietary-induced weight gain and increase insulin sensitivity in mice. Ten-week-old, male, C57BL/6J mice were fed a diet containing 60% fat calories and water supplemented with 11% sucrose for 4 weeks. Groups () received one of the following: CORT 108297 (80 mg/kg QD), CORT 108297 (40 mg/kg BID), mifepristone (30 mg/kg BID), rosiglitazone (10 mg/kg QD), or vehicle. Compared to mice receiving a high-fat, high-sugar diet plus vehicle, mice receiving a high-fat, high-sugar diet plus either mifepristone or CORT 108297 gained significantly less weight. At the end of the four week treatment period, mice receiving CORT 108297 40 mg/kg BID or CORT 108297 80 mg/kg QD also had significantly lower steady plasma glucose than mice receiving vehicle. However, steady state plasma glucose after treatment was not highly correlated with reduced weight gain, suggesting that the effect of the glucocorticoid receptor antagonist on insulin sensitivity may be independent of its mitigating effect on weight gain.
A Review of Weight Control Strategies and Their Effects on the Regulation of Hormonal Balance
Authors: Schwarz Neil A. , Rigby B. Rhett , La Bounty Paul , Shelmadine Brian , Bowden Rodney G.
Published: July 2011

The estimated prevalence of obesity in the USA is 72.5 million adults with costs attributed to obesity more than 147 billion dollars per year. Though caloric restriction has been used extensively in weight control studies, short-term success has been difficult to achieve, with long-term success of weight control being even more elusive. Therefore, novel approaches are needed to control the rates of obesity that are occurring globally. The purpose of this paper is to provide a synopsis of how exercise, sleep, psychological stress, and meal frequency and composition affect levels of ghrelin, cortisol, insulin GLP-1, and leptin and weight control. We will provide information regarding how hormones respond to various lifestyle factors which may affect appetite control, hunger, satiety, and weight control.
Psoas Abscess Formation in Suboptimally Controlled Diabetes Mellitus
Authors: Lansdown A. J. , Downing A. , Roberts A. W. , Martin D.
Published: July 2011

Psoas abscess formation is a rare entity for which diabetes mellitus remains a major predisposing factor. Diabetes has long been associated with a predisposition to unusual and more serious infections. Here we present two cases that demonstrate that chronically suboptimally controlled diabetes remains an important marker for the development of primary psoas abscess. It is important to include psoas abscess in the differential in such patients to ensure early diagnosis and treatment.
Testing Strategies for Detection of Xenotropic Murine Leukemia Virus-Related Virus Infection
Authors: Tang Shixing , Hewlett Indira K.
Published: July 2011

Xenotropic murine leukemia virus-related virus (XMRV) is a newly identified gamma retrovirus and may be associated with prostate cancer- (PC) and chronic fatigue syndrome (CFS). Since its identification in 2006 and detection of polytropic murine lenkemia virus (MLV)-like sequences in CFS patients in 2010, several test methods including nucleic acid testing methods and serological assays have been developed for detection of XMRV and/or MLV-like sequences. However, these research assays have not yet been validated and evaluated due to the lack of well-characterized reference materials. Mouse DNA contamination should be carefully checked when testing human specimens in order to avoid false-positive detection of XMRV or MLV-like sequences.
Optimization of the Preparation Process for an Oral Phytantriol-Based Amphotericin B Cubosomes
Authors: Yang Zhiwen , Peng Xinsheng , Tan Yinhe , Chen Meiwan , Zhu Xingqi , Feng Min , Xu Yuehong , Wu Chuanbin
Published: July 2011

In order to develop an oral formation of Amphotericin B (AmB) using phytantriol- (PYT-) based cubosomes with desirable properties, homogenization conditions were firstly investigated to determine their effects on the morphological and dimensional characteristics of cubosomes. Under the optimized homogenization conditions of 1200 bar for 9 cycles, cubosomes with reproducible, narrow particle size distribution and a mean particle size of 256.9 nm ± 4.9 nm were obtained. The structure of the dispersed cubosomes was revealed by SAXS (small-angle X-ray scattering) and Cryo-TEM (cryogenic transmission electron microscopy) as a bicontinuous cubic liquid crystalline phase with Pn3m geometry. To overcome the poor drug solubility and increase the drug-loading rate, a solubilization method was firstly used to develop cubosomes containing AmB. The encapsulation efficiency determined by HPLC assay was87.8%±3.4%, and UV spectroscopy and stability studies in simulated gastric fluids further confirmed that AmB was successfully encapsulated in cubosomes.
Can Better Mother-Daughter Relations Reduce the Chance of a Suicide Attempt among Latinas?
Authors: Zayas Luis H. , Hausmann-Stabile Carolina , Kuhlberg Jill
Published: July 2011

National surveys and other research on adolescent Latinas show that adolescent females have higher rates of suicidal ideation, planning, and attempts than other ethnic and racial minority youth. Internalizing behaviors and family conflicts are commonly associated with suicidality in research on adolescents. In the case of Latinas, we explore the connection between adolescent Hispanic cultural involvement, mother-adolescent mutuality, internalizing behaviors, and suicidality. This paper presents data from a study of 232 Latinas, some with a recent history of suicide attempts (n=122). The results show that higher adolescent Hispanic cultural involvement was associated with greater mother-daughter mutuality and thus led to reduction in the likelihood of suicide attempts. The relationship between mother-daughter mutuality and suicide attempts among Latinas is mediated by specific internalizing behaviors (withdrawn depressive). Our findings highlight the positive effect that Latino cultural values have in the relationship between Latina adolescent and their mothers and confirm the importance that internalizing behaviors and the mother-daughter relationship have for suicide attempters.
A Novel Route for Development of Bulk Al/SiC Metal Matrix Nanocomposites
Authors: Padhi Payodhar , Kar Sachikanta
Published: July 2011

Addition of nano particles, even in quantities as small as 2 weight percent can enhance the hardness or yield strength by a factor as high as 2. There are several methods for the production of metal matrix nanocomposites including mechanical alloying, vertex process, and spray deposition and so forth. However, the above processes are expensive. Solidification processing is a relatively cheaper route. During solidification processing, nano particulates tend to agglomerate as a result of van der Waals forces and thus proper dispersion of the nano particulate in metal matrix is a challenge. In the present study a noncontact method, where the ultrasonic probe is not in direct contact with the liquid metal, was attempted to disperse nanosized SiC particulates in aluminum matrix. In this method, the mold was subjected to ultrasonic vibration. Hardness measurements and microstructural studies using HRTEM were carried out on samples taken from different locations of the nanocomposite ingot cast by this method.
Stability of the Pexiderized Lobacevski Equation
Authors: Kim Gwang Hui
Published: July 2011

The aim of this paper is to investigate the solution and the superstability of the Pexiderized Lobacevski equation f((x + y)/2) 2 = g(x)h(y), where f, g, h : G2 → ℂ are unknown functions on an Abelian semigroup (G, +). The obtained result is a generalization of Gǎvruţa′s result in 1994 and Kim′s result in 2010.
Coupling and Shielding Properties of the Baffle in ICP System
Authors: Brcka Jozef , Robison R. Lee
Published: July 2011

This contribution is dealing with experimental and computational evaluation of the deposition baffle that is transparent to radio frequency (RF) magnetic fields generated by an external antenna in an inductively coupled plasma (ICP) source but opaque to the deposition of the metal onto a dielectric wall in ionized physical vapor deposition (IPVD) system. Various engineering aspects related to the deposition baffle are discussed. Among the many requirements focus is on specific structure of the slots and analysis to minimize deposition on the baffle (we used a string model for simulating the profile evolution) and deposition through the DB on dielectric components of the ICP source. Transparency of the baffle to RF magnetic fields is computed using a three‐dimensional (3D) electromagnetic field solver. A simple two‐dimensional sheath model is used to understand plasma interactions with the DB slot structure. Performance and possible failure of device are briefly discussed.
Manipulation of Polyhydroxybutyrate Properties through Blending with Ethyl-Cellulose for a Composite Biomaterial
Authors: Chan Rodman T. H. , Garvey Christopher J. , Marçal Helder , Russell Robert A. , Holden Peter J. , Foster L. John R.
Published: July 2011

Polyhydroxybutyrate (PHB) is widely used as a biomaterial in medical and tissue-engineering applications, a relatively high crystallinity limits its application. Blending PHB with ethyl-cellulose (EtC) was readily achieved to reduce PHB crystallinity and promote its degradation under physiological conditions without undue influence on biocompatibility. Material strength of composite films remained unchanged at 6.5±0.6 MPa with 40% (w/w) EtC loadings. Phase separation between the two biopolymers was determined with PHB crystallinity decreasing from 63% to 47% for films with the same loading. This reduction in crystallinity supported an increase in the degradation rates of composite films from 0.39 to 0.81% wk−1for PHB and its composite, respectively. No significant change in morphology and proliferation of olfactory ensheathing cells were observed with the composites despite significant increases in average surface roughness (Ra) of the films from 2.90 to 3.65 μm for PHB and blends with 80% (w/w) EtC, respectively.
Lipids, Lipoproteins, and Age-Related Macular Degeneration
Authors: Ebrahimi Katayoon B. , Handa James T.
Published: July 2011

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly. While excellent treatment has emerged for neovascular disease, treatment for early AMD is lacking due to an incomplete understanding of the early molecular events. A prominent age-related change is the accumulation of neutral lipid in normal Bruch's membrane (BrM) throughout adulthood and also disease-related BrM accumulations called basal deposits and drusen. AMD lesion formation has thus been conceptualized as sharing mechanisms with atherosclerotic plaque formation, where low-density lipoprotein (LDL) retention within the arterial wall initiates a cascade of pathologic events. However, we do not yet understand how lipoproteins contribute to AMD. This paper explores how systemic and local production of lipoproteins might contribute to the pathogenesis of AMD.
Combinatorial Treatments That Overcome PDGFRβ-Driven Resistance of Melanoma Cells to V600EB-RAF Inhibition
Authors: Shi Hubing , Kong Xiangju , Ribas Antoni , Lo Roger S.
Published: July 2011

V600EB-RAF mutation is found in 50% to 60% of melanomas, and the novel agents PLX4032/vemurafenib and GSK2118436 that inhibit the V600EB-RAF kinase achieve a remarkable clinical response rate. However, as might be expected, acquired clinical resistance to these agents arises in most melanoma patients. PLX4032/vemurafenib resistance that arises in vivo in tumor matched short-term cultures or in vitro in melanoma cell lines is not caused by acquisition of secondary mutations in V600EB-RAF but rather is caused by upregulating platelet-derived growth factor receptor β (PDGFRβ) or N-RAS which results in resistance or sensitivity to mitogen-activated protein (MAP)/extracellular signal-regulated (ERK; MEK) kinase inhibitors, respectively. In this study, we define a targeted combinatorial strategy to overcome PLX4032/vemurafenib resistance in melanoma cell lines or short-term culture where the resistance is driven by PDGFRβ upregulation, achieving synergistic growth inhibition and cytotoxicity. PDGFRβ-upregulated, PLX4032-resistant (PPRM) cell lines show dual phospho (p)-ERK and p-AKT upregulation, and their growth inhibitory responses to specific small molecule inhibitors correlated with p-ERK, p-AKT, and p-p70S6K levels. Coordinate inhibition of V600EB-RAF inhibition and the RTK–PI3K–AKT–mTORC axis led to functionally significant rebound signaling, illustrating a robust and dynamic network connectivity. Combined B-RAF, phosphoinositide 3-kinase (PI3K), and mTORC1/2 inhibition suppressed both immediate early and delayed compensatory signaling, resulting in a highly synergistic growth inhibitory response but less efficient cytotoxic response. In contrast, the combination of MEK1/2, PI3K, and mTORC1/2 inhibitors consistently triggered apoptosis in a highly efficient manner. Together, our findings offer a rational strategy to guide clinical testing in preidentified subsets of patients who relapse during treatment with V600EB-RAF inhibitors. Cancer Res; 71(15); 5067–74. ©2011 AACR.
Should eGFR and Albuminuria Be Added to the Framingham Risk Score Chronic Kidney Disease and Cardiovascular Disease Risk Prediction
Authors: Chang Alex , Kramer Holly
Published: July 2011

Presence of chronic kidney disease (CKD) defined as decreased glomerular filtration rate (GFR) and/or increased urine albumin excretion is associated with heightened risk of cardiovascular disease (CVD) and all-cause as well as CVD mortality. Although CKD is strongly linked with CVD, it remains undetermined whether this strong association is simply due to shared CVD risk factors or unique traits consequential to CKD. The probability of future CVD events can be estimated with reasonable accuracy using the Framingham equation which was derived from the Framingham study, a community-based cohort of 5,209 white adults aged 30–62 years who were first examined in 1948. Efforts to capture excess CVD risk associated with CKD have been evaluated by adding estimated GFR, cystatin C, serum creatinine and measures of urinary albumin excretion to the Framingham equation which is based on traditional cardiovascular risk factors. Although decreased GFR and increased urine albumin excretion are consistently associated with cardiovascular outcomes, the addition of these factors to the Framingham equation has not been shown to substantially improve overall CVD risk prediction in populations not enriched with CKD. Moreover, the Framingham equation itself underpredicts cardiovascular events among adults with stage 3 and 4 CKD without clinical CVD. Given the poor performance of the Framingham equation in adults with CKD, future studies should explore risk equations which include traditional CVD risk factors and the unique comorbidities associated with CKD for prediction of cardiovascular events in adults with CKD.
Bright-Light Therapy in the Treatment of Mood Disorders
Authors: Pail Gerald , Huf Wolfgang , Pjrek Edda , Winkler Dietmar , Willeit Matthaeus , Praschak-Rieder Nicole , Kasper Siegfried
Published: July 2011

Bright-light therapy (BLT) is established as the treatment of choice for seasonal affective disorder/winter type (SAD). In the last two decades, the use of BLT has expanded beyond SAD: there is evidence for efficacy in chronic depression, antepartum depression, premenstrual depression, bipolar depression and disturbances of the sleep-wake cycle. Data on the usefulness of BLT in non-seasonal depression are promising; however, further systematic studies are still warranted. In this review, the authors present a comprehensive overview of the literature on BLT in mood disorders. The first part elucidates the neurobiology of circadian and seasonal adaptive mechanisms focusing on the suprachiasmatic nucleus (SCN), the indolamines melatonin and serotonin, and the chronobiology of mood disorders. The SCN is the primary oscillator in humans. Indolamines are known to transduce light signals into cells and organisms since early in evolution, and their role in signalling change of season is still preserved in humans: melatonin is synthesized primarily in the pineal gland and is the central hormone for internal clock circuitries. The melatonin precursor serotonin is known to modulate many behaviours that vary with season. The second part discusses the pathophysiology and clinical specifiers of SAD, which can be seen as a model disorder for chronobiological disturbances and the mechanism of action of BLT. In the third part, the mode of action, application, efficacy, tolerability and safety of BLT in SAD and other mood disorders are explored.
A Multicenter Brain Perfusion SPECT Study Evaluating Idiopathic Normal-Pressure Hydrocephalus on Neurological Improvement
Authors: Ishii Kazunari , Hashimoto Masaaki , Hayashida Kohei , Hashikawa Kazuo , Chang Chia-Cheng , Nakagawara Jyoji , Nakayama Teiji , Mori Satoru , Sakakibara Ryuji
Published: July 2011

Purpose: This study was designed to investigate the specific cerebral blood flow (CBF) pattern in patients with idiopathic normal-pressure hydrocephalus (iNPH) and a predictive value for shunt responsiveness in a multicenter study (Study of Idiopathic Normal-Pressure Hydrocephalus on Neurological Improvement: SINPHONI). Methods: Eighty-four iNPH patients underwent shunt operations using MRI selection criteria from the SINPHONI and were subjected to CBF single photon emission computed tomography (SPECT). The perfusion patterns on SPECT were classified: anterior-dominant CBF reduction type (A type), posterior-dominant CBF reduction type (P type), and mixed or diffuse CBF reduction type (M type). The predictive value of the CBF pattern for favorable shunt outcome was evaluated. Results: Favorable outcomes were obtained in 76% (64/84) of patients, and shunt responsiveness was achieved in 85% (71/84) of patients. Areas of severely reduced relative CBF were demonstrated around the corpus callosum and in the sylvian fissure area, which included the effects of dilatations of the ventricles and sylvian fissures and relatively increased perfusion in the medial and lateral frontal, parietal, and occipital areas at high convexity. Forty-nine (58%) cases were A type, 25 (30%) cases were M type, and 10 (12%) cases were P type. A, M, and P type cases exhibited 83, 84, and 90% positive predictive values for shunt responsiveness, respectively. Mean modified Rankin scale and Mini-Mental State Examination scores of the A type group were significantly better than those of other groups. Conclusion: The iNPH patients showed various patterns of CBF reduction, but there was no significant difference in the predictive value among the three patterns, though CBF reduction patterns may suggest a severe condition of iNPH.
Use of Online Conductivity Monitoring to Study Sodium Mass Balance in Chronic Haemodialysis Patients: Prospects for Treatment Individualisation
Authors: Odudu Aghogho , Lambie Stewart , Taal Maarten W. , Fluck Richard J. , McIntyre Christopher W.
Published: July 2011

Background: Failure to achieve isonatric haemodialysis (HD) drives an expansion of extracellular volume leading to increased interdialytic weight gain (IDWG). This may be a causative factor in the development of HD-induced cardiac injury. We examined total and diffusive sodium mass balance during HD. Methods: 24 chronic HD patients using a fixed 140 mmol/l sodium concentration were studied over 4 weeks. Dialysate and plasma conductivity and ionic mass balance (IMB) were recorded. IMB estimates total ionic transfer across the HD membrane. Results: Mean total IMB was 338 mmol indicating net sodium removal. Intrapatient variability was less than interpatient variability (coefficient of variation = 42 vs. 26%, respectively). The diffusive component of ionic mass balance (IMBdiff) was 97 ± 18 mmol approximating 29% (±22–36) of total sodium removal. IMBdiff also correlated with both plasma conductivity and predialysis plasma sodium (r2 = 0.82 and 0.6, respectively; p < 0.0001) as well as the reduction in plasma conductivity and plasma sodium during HD (r2 = 0.7 and 0.5, respectively; p < 0.0001). Conclusion: HD against a fixed dialysate sodium concentration of 140 mmol/l results in a wide range of sodium removal with a mean of 29% removed by diffusion. Online conductivity monitoring can be utilized as part of a variety of strategies to enable the delivery of individualised and isonatric HD. Further study is required to explore the utility of such strategies which may be crucial in reducing IDWG and HD-induced cardiac injury.
PSEUDOMARKER: A Powerful Program for Joint Linkage and/or Linkage Disequilibrium Analysis on Mixtures of Singletons and Related Individuals
Authors: Hiekkalinna Tero , Schäffer Alejandro A. , Lambert Brian , Norrgrann Petri , Göring Harald H.H. , Terwilliger Joseph D.
Published: July 2011

A decade ago, there was widespread enthusiasm for the prospects of genome-wide association studies to identify common variants related to common chronic diseases using samples of unrelated individuals from populations. Although technological advancements allow us to query more than a million SNPs across the genome at low cost, a disappointingly small fraction of the genetic portion of common disease etiology has been uncovered. This has led to the hypothesis that less frequent variants might be involved, stimulating a renaissance of the traditional approach of seeking genes using multiplex families from less diverse populations. However, by using the modern genotyping and sequencing technology, we can now look not just at linkage, but jointly at linkage and linkage disequilibrium (LD) in such samples. Software methods that can look simultaneously at linkage and LD in a powerful and robust manner have been lacking. Most algorithms cannot jointly analyze datasets involving families of varying structures in a statistically or computationally efficient manner. We have implemented previously proposed statistical algorithms in a user-friendly software package, PSEUDOMARKER. This paper is an announcement of this software package. We describe the motivation behind the approach, the statistical methods, and software, and we briefly demonstrate PSEUDOMARKER’s advantages over other packages by example.
Projection from the Cochlear Nucleus to the Peripheral Vestibule in Wistar Rats
Authors: Wang Jing , Chi Fang-lu , Zhao Hao , Xin Yuan
Published: July 2011

Objective: To find morphological evidence of a direct projection from the cochlear nucleus (CN; at the brainstem level) in the auditory system to the peripheral end organs in the vestibular system. Methods: Experiments were conducted on male Wistar rats (n = 24). Two neuronal tracers were used: (1) 5% molecular probe F-8793 was injected into the unilateral peripheral vestibule and used as a retrograde tracer; (2) PHA-L (Invitrogen L-11270) was injected into the unilateral CN and used as an anterograde tracer. All animals were allowed to recover for 7 days after surgery to facilitate sufficient transportation of the tracers. Subsequently, brainstems in the retrograde group and inner ears in the anterograde group were sliced coronally on a freezing microtome and observed under a fluorescence microscope. Results: After PHA-L injection into the CN, terminal labeling was observed in the peripheral vestibule, especially in the inferior vestibular nerve. The retrograde tracing study showed that the positive cells could be found in the ventral part of the CN. Conclusions: These results suggest that there is a novel pathway with a consanguineous functional connection between the CN and peripheral vestibule.
Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists
Authors: Marchesi Chiara , Pierfranceschi Matteo , Crowther Mark , Garcia David , Hylek Elaine , Witt Daniel , Clark Nathan , Squizzato Alessandro , Imberti Davide , Ageno Walter , Dentali Francesco
Published: July 2011

Prothrombin complex concentrates (PCCs) are recommended as the treatment of choice in warfarin-related coagulopathy. However, the risk of thromboembolic complications associated with their use is not well defined. We performed a meta-analysis to estimate the rate of thromboembolic complications in patients receiving vitamin K antagonists (VKAs) treated with PCCs for bleeding or before urgent surgery. Medline and Embase databases were searched. Two reviewers performed study selection and extracted data independently. Studies providing data on incidence of thromboembolic complications in VKA-treated patients were eligible for the study. Weighted mean proportion of the rate of thromboembolic complications and the mortality rate were calculated. Twenty-seven studies (1,032 patients) were included. Seven studies used 3-factor, and 20 4-factor PCCs. Twelve patients had a thromboembolic complication (weighted mean 1.4%; 95% CI 0.8–2.1), of which two were fatal. The incidence of thromboembolic events was 1.8% (95% CI 1.0–3.0) in patients treated with 4-factor PCCs, and 0.7% (95% CI 0.0–2.4) in patients treated with 3-factor PCCs. Total mortality rate was 10.6% (95% CI 5.9–16.6). In conclusion, our results suggest there is a low but quantifiable risk of thromboembolism in VKA-treated patients receiving PCCs for anticoagulation reversal. These findings should be confirmed in randomised, controlled trials.
Telethonin Deficiency Is Associated With Maladaptation to Biomechanical Stress in the Mammalian Heart
Authors: Knöll Ralph , Linke Wolfgang A. , Zou Peijian , Miočiċ Snježana , Kostin Sawa , Buyandelger Byambajav , Ku Ching-Hsin , Neef Stefan , Bug Monika , Schäfer Katrin , Knöll Gudrun , Felkin Leanne E. , Wessels Johannes , Toischer Karl , Hagn Franz , Kessler Horst , Didié Michael , Quentin Thomas , Maier Lars S. , Teucher Nils , Unsöld Bernhard , Schmidt Albrecht , Birks Emma J. , Gunkel Sylvia , Lang Patrick , Granzier Henk , Zimmermann Wolfram-Hubertus , Field Loren J. , Faulkner Georgine , Dobbelstein Matthias , Barton Paul J.R. , Sattler Michael , Wilmanns Matthias , Chien Kenneth R.
Published: July 2011

Rationale:

Telethonin (also known as
titin-cap
or
t-cap
) is a 19-kDa Z-disk protein with a unique β-sheet structure, hypothesized to assemble in a palindromic way with the N-terminal portion of titin and to constitute a signalosome participating in the process of cardiomechanosensing. In addition, a variety of telethonin mutations are associated with the development of several different diseases; however, little is known about the underlying molecular mechanisms and telethonin's in vivo function.

Objective:

Here we aim to investigate the role of telethonin in vivo and to identify molecular mechanisms underlying disease as a result of its mutation.

Methods and Results:

By using a variety of different genetically altered animal models and biophysical experiments we show that contrary to previous views, telethonin is not an indispensable component of the titin-anchoring system, nor is deletion of the gene or cardiac specific overexpression associated with a spontaneous cardiac phenotype. Rather, additional titin-anchorage sites, such as actin–titin cross-links via α-actinin, are sufficient to maintain Z-disk stability despite the loss of telethonin. We demonstrate that a main novel function of telethonin is to modulate the turnover of the proapoptotic tumor suppressor p53 after biomechanical stress in the nuclear compartment, thus linking telethonin, a protein well known to be present at the Z-disk, directly to apoptosis (“mechanoptosis”). In addition, loss of telethonin mRNA and nuclear accumulation of this protein is associated with human heart failure, an effect that may contribute to enhanced rates of apoptosis found in these hearts.

Conclusions:

Telethonin knockout mice do not reveal defective heart development or heart function under basal conditions, but develop heart failure following biomechanical stress, owing at least in part to apoptosis of cardiomyocytes, an effect that may also play a role in human heart failure.
Plaque Distribution of Stenotic Middle Cerebral Artery and Its Clinical Relevance
Authors: Xu Wei-Hai , Li Ming-Li , Gao Shan , Ni Jun , Zhou Li-Xin , Yao Ming , Peng Bin , Feng Feng , Jin Zheng-Yu , Cui Li-Ying
Published: July 2011

Background and Purpose—

Microanatomy studies reveal that most penetrating branches of middle cerebral artery (MCA) arise from the dorsal–superior surface of the trunk. Using high-resolution MRI, we sought to explore the plaque distribution of MCA atherosclerosis and its clinical relevance in relation to the orifices of penetrating arteries.

Methods—

We retrospectively analyzed the imaging and clinical data of 86 patients with atherosclerotic MCA stenosis. On high-resolution MRI, plaques were categorized based on the involvement of the superior, inferior, ventral, or dorsal MCA wall. The relationship of plaque distribution and clinical presentation was analyzed.

Results—

A total of 92 stenotic MCAs (40 symptomatic and 52 asymptomatic) on 828 image slices were studied. Overall, of the 251 slices with identified plaques, plaques were more frequently located at the ventral (44.8%) and inferior (31.7%) wall as compared with the superior (14.3%) and dorsal wall (9.0%;
P
<0.001). Symptomatic MCA stenosis had more superior (
P
=0.016) and less inferior (
P
=0.023) wall plaques than asymptomatic stenosis. Within the group of symptomatic MCA stenosis, vessels with penetrating artery infarctions had more superior (
P
=0.001) but less ventral (
P
=0.038) and inferior (
P
=0.024) plaques than without penetrating artery infarctions.

Conclusions—

MCA plaques tend to locate opposite to the orifices of penetrating arterial branches. Further studies are required to investigate whether MCA plaque distribution is an independent determinant of stroke occurrence and its subtypes.
Effects of Extending the Time Window of Thrombolysis to 4.5 Hours
Authors: Asplund Kjell , Glader Eva-Lotta , Norrving Bo , Eriksson Marie ,   for the Riks-Stroke Collaboration
Published: July 2011

Background and Purpose—

The European Cooperative Acute Stroke Study (ECASS) III trial and Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register (SITS-ISTR) data were published in 2008. Riks-Stroke, the Swedish Stroke Register, was used to explore how thrombolysis in the 3- to 4.5-hour window has been spread in different hospitals and patient groups and what effects this has had on treatment within 3 hours.

Methods—

All 76 hospitals in Sweden admitting patients with acute stroke participate in Riks-Stroke. During the study period, January 2003 to June 2010, 92 150 18- to 80-year-old patients were hospitalized for acute ischemic stroke.

Results—

After the publication of the ECASS III results in the third quarter of 2008, thrombolysis in the 3- to 4.5-hour window increased from 0.5% before publication to 2.1% in 2010. Thrombolysis in the 3- to 4.5-hour window spread somewhat faster in men than women (
P
=0.04) but at a similar rate in different age groups. The use of thrombolysis within 3 hours after onset of symptoms increased successively from 0.9% in 2003 to 6.6% in late 2008 and then it stabilized at 6%. The median time from arrival to the hospital to start of treatment remained unchanged at 66 to 69 minutes before and after 2008 (
P
=0.06).

Conclusions—

Since the end of 2008, there has been a rapid nationwide dissemination of thrombolysis in the 3- to 4.5-hour window, whereas rates in the <3-hour window have leveled off. The extended time window has not affected door-to-needle time.
Lobbying Allies? The NSZZ Solidarność Coordinating Office Abroad, 1982–1989
Authors: Goddeeris Idesbald
Published: July 2011

After the proclamation of martial law in Poland in December 1981, a Solidarność Coordinating Office Abroad was set up. Led by Jerzy Milewski, the organization eliminated any internal opposition and succeeded in being recognized by most Western partners as the foreign representative of Solidarność. The Coordinating Office received most of its financial aid from trade union internationals and from the United States. Initially, the Coordinating Office was active mainly within international institutions such as the Conference on Security and Cooperation in Europe and the International Labor Organization. From 1984 onward, the organization sought to influence senior politicians and governments and became an important reminder to the Western world of the Polish crisis, as well as providing financial and material aid to the banned Polish trade union. However, it did not have a definitive impact on policymaking and remained largely dependent on its allied organizations.
U.S. Conduct in the Vietnam War: Commentaries on Bernd Greiner's War without Fronts
Authors: Bacevich Andrew J. , Moïse Edwin , Lawrence Mark Atwood , Greiner Bernd
Published: July 2011

Three leading experts on the Vietnam War and U.S. foreign policy offer separate evaluations of Bernd Greiner's book War without Fronts: The USA in Vietnam. The book presents a harsh and controversial appraisal of the conduct of U.S. troops in Vietnam, depicting the My Lai massacre not as an aberration but as one of a long series of atrocities committed by U.S. personnel. The three commentators diverge in their assessments of the book. Andrew Bacevich and Edwin Moïse sharply criticize the book, which they see as one-sided and often tendentious, selective, and inaccurate in its use of evidence. Bacevich argues that the book is intended in part, if only subconsciously, to bolster revisionist German claims about the conduct of Germany during the Second World War, and Moïse casts doubt on Greiner's use of key sources. Mark Lawrence, by contrast, praises the book and believes that it will help to refocus study of U.S. conduct in Vietnam. The forum concludes with a reply by Greiner to the three commentaries.
Orthodox Theology of Personhood: A Critical Overview (Part 2)
Authors: Lubardić Bogdan
Published: July 2011

This paper offers a critical overview of the more recent Orthodox theology of personhood. This theology is put into perspective in terms of overviewing its development and transmission between four notable exponents: Lossky, Yannaras, Zizioulas and Horuzhy. The model of personhood they share is shown to be re-received and specifically reworked by each, not without sparks of mutual critique. Still, the general tendency is to make the conception of personhood more ecclesially and anthropologically relevant. Critical consequences of this of theological tought are not to be understood narrowly. For they ramify to bear upon epistemology, ontology, philosophy, theology proper and ethics. Apart from fruitful solutions to the questions raised by thematizing the challenge of personhood (as immanent to our being image-bearers of God), we display entry points for critical problematization of this Orthodox current of thought. Hence critical consequences of the theology of personhood are not articulated without reference to the meta-critique of it, as offered by a third generation of Orthodox theologians. We propose to view this process in general as a birth of a ‘theological age’ of sorts: the nascent of ecclesial understanding of our personhood in God.
Venezuela and military expenditure data
Authors: Colgan Jeff
Published: July 2011

The Stockholm International Peace Research Institute (SIPRI) and the International Institute of Strategic Studies (IISS) both publish datasets on military expenditure that are widely used by scholars and military analysts. This article illustrates the limitations in the reliability and validity of these data, using a case study of contemporary Venezuela to highlight the issues. There is a debate over recent Venezuelan military expenditure under President Chávez: some argue that the expenditure has increased dramatically; others argue that it has not. The SIPRI and IISS datasets ought to be tailor-made for resolving this debate, but the estimates they provide are significantly flawed: military spending is reported to be quite low and to have declined as a percentage of GDP. New evidence presented in this article suggests that Venezuela’s recent military expenditures were typically at least 20% to 70% higher than the estimates provided by SIPRI and IISS. Moreover, the military expenditures have at least kept pace with GDP growth as oil revenues increased over the period 2002–08. A key source of the discrepancy in the estimates is the way in which extra-budgetary purchases, especially of foreign arms and supplies, are treated. In some states, such as Venezuela in recent years, extra-budgetary purchases are responsible for a large portion of the expenditure, but these purchases are frequently not captured by standard data sources.
Teacher Perceptions of Teacher Leadership
Authors: Angelle Pamela S. , DeHart Corey A.
Published: July 2011

Researchers for this multisite quantitative study examined the relationships between teacher perceptions of the extent of teacher leadership in a school and the grade level, degree level, and leadership status of the respondents. Data for this study were collected in two administrations in 43 schools in seven U.S. states. To test for differences among the variables and the four factors of the Teacher Leadership Inventory, a one-way ANOVA was conducted for each variable. Findings indicated significant differences between elementary school teachers and middle/high school teachers, teachers with a bachelor’s degree and teachers with graduate degrees, and formal teacher leaders and teachers in no leadership position. Attention to these results will allow school districts to better align leadership training with the needs of specific teachers and support principals in school improvement.
The Impact of Stigma in Healthcare on People Living with Chronic Illnesses
Authors: Earnshaw Valerie A. , Quinn Diane M.
Published: July 2011

Approximately half of adults are living with a chronic illness, many of whom may feel stigmatized by their chronic illness in different contexts. We explored the impact of internalized, experienced, and anticipated stigma within healthcare settings on the quality of life of 184 participants living with chronic illnesses (e.g. diabetes, inflammatory bowel disease, asthma). Results of a path analysis demonstrate that participants who internalized stigma and experienced stigma from healthcare workers anticipated greater stigma from healthcare workers. Participants who anticipated greater stigma from healthcare workers, in turn, accessed healthcare less and experienced a decreased quality of life.
Notch1 controls macrophage recruitment and Notch signaling is activated at sites of endothelial cell anastomosis during retinal angiogenesis in mice
Authors: Outtz Hasina H. , Tattersall Ian W. , Kofler Natalie M. , Steinbach Nicole , Kitajewski Jan
Published: July 2011

Notch is a critical regulator of angiogenesis, vascular differentiation, and vascular integrity. We investigated whether Notch signaling affects macrophage function during retinal angiogenesis in mice. Retinal macrophage recruitment and localization in mice with myeloid-specific loss of Notch1 was altered, as these macrophages failed to localize at the leading edge of the vascular plexus and at vascular branchpoints. Furthermore, these retinas were characterized by elongated endothelial cell sprouts that failed to anastomose with neighboring sprouts. Using Notch reporter mice, we demonstrate that retinal macrophages localize between Dll4-positive tip cells and at vascular branchpoints, and that these macrophages had activated Notch signaling. Taken together, these data demonstrate that Notch signaling in macrophages is important for their localization and interaction with endothelial cells during sprouting angiogenesis.
Erythrocyte peripheral type benzodiazepine receptor/voltage-dependent anion channels are upregulated by Plasmodium falciparum
Authors: Bouyer Guillaume , Cueff Anne , Egée Stéphane , Kmiecik Justyna , Maksimova Yelena , Glogowska Edyta , Gallagher Patrick G. , Thomas Serge L. Y.
Published: July 2011

Plasmodium falciparum relies on anion channels activated in the erythrocyte membrane to ensure the transport of nutrients and waste products necessary for its replication and survival after invasion. The molecular identity of these anion channels, termed “new permeability pathways” is unknown, but their currents correspond to up-regulation of endogenous channels displaying complex gating and kinetics similar to those of ligand-gated channels. This report demonstrates that a peripheral-type benzodiazepine receptor, including the voltage dependent anion channel, is present in the human erythrocyte membrane. This receptor mediates the maxi-anion currents previously described in the erythrocyte membrane. Ligands that block this peripheral-type benzodiazepine receptor reduce membrane transport and conductance in P falciparum-infected erythrocytes. These ligands also inhibit in vitro intraerythrocytic growth of P falciparum. These data support the hypothesis that dormant peripheral-type benzodiazepine receptors become the “new permeability pathways” in infected erythrocytes after up-regulation by P falciparum. These channels are obvious targets for selective inhibition in anti-malarial therapies, as well as potential routes for drug delivery in pharmacologic applications.
Differences in cortical response to acupressure and electroacupuncture stimuli
Authors: Witzel Thomas , Napadow Vitaly , Kettner Norman W , Vangel Mark G , Hämäläinen Matti S , Dhond Rupali P
Published: July 2011

Background

FMRI studies focus on sub-cortical effects of acupuncture stimuli. The purpose of this study was to assess changes in primary somatosensory (S1) activity over the course of different types of acupuncture stimulation. We used whole head magnetoencephalography (MEG) to map S1 brain response during 15 minutes of electroacupuncture (EA) and acupressure (AP). We further assessed how brain response changed during the course of stimulation.

Results

Evoked brain response to EA differed from AP in its temporal dynamics by showing clear contralateral M20/M30 peaks while the latter demonstrated temporal dispersion. Both EA and AP demonstrated significantly decreased response amplitudes following five minutes of stimulation. However, the latency of these decreases were earlier in EA (~30 ms post-stimulus) than AP (> 100 ms). Time-frequency responses demonstrated early onset, event related synchronization (ERS), within the gamma band at ~70-130 ms and the theta band at ~50-200 ms post-stimulus. A prolonged event related desynchronization (ERD) of alpha and beta power occurred at ~100-300 ms post-stimulus. There was decreased beta ERD at ~100-300 ms over the course of EA, but not AP.

Conclusion

Both EA and AP demonstrated conditioning of SI response. In conjunction with their subcortical effects on endogenous pain regulation, these therapies show potential for affecting S1 processing and possibly altering maladaptive neuroplasticity. Thus, further investigation in neuropathic populations is needed.
Wide cross-reactivity between Anopheles gambiae and Anopheles funestus SG6 salivary proteins supports exploitation of gSG6 as a marker of human exposure to major malaria vectors in tropical Africa
Authors: Rizzo Cinzia , Ronca Raffaele , Fiorentino Gabriella , Mangano Valentina D , Sirima Sodiomon B , Nèbiè Issa , Petrarca Vincenzo , Modiano David , Arcà Bruno
Published: July 2011

Background

The Anopheles gambiae gSG6 is an anopheline-specific salivary protein which helps female mosquitoes to efficiently feed on blood. Besides its role in haematophagy, gSG6 is immunogenic and elicits in exposed individuals an IgG response, which may be used as indicator of exposure to the main African malaria vector A. gambiae. However, malaria transmission in tropical Africa is sustained by three main vectors (A. gambiae, Anopheles arabiensis and Anopheles funestus) and a general marker, reflecting exposure to at least these three species, would be especially valuable. The SG6 protein is highly conserved within the A. gambiae species complex whereas the A. funestus homologue, fSG6, is more divergent (80% identity with gSG6). The aim of this study was to evaluate cross-reactivity of human sera to gSG6 and fSG6.

Methods

The A. funestus SG6 protein was expressed/purified and the humoral response to gSG6, fSG6 and a combination of the two antigens was compared in a population from a malaria hyperendemic area of Burkina Faso where both vectors were present, although with a large A. gambiae prevalence (>75%). Sera collected at the beginning and at the end of the high transmission/rainy season, as well as during the following low transmission/dry season, were analysed.

Results

According to previous observations, both anti-SG6 IgG level and prevalence decreased during the low transmission/dry season and showed a typical age-dependent pattern. No significant difference in the response to the two antigens was found, although their combined use yielded in most cases higher IgG level.

Conclusions

Comparative analysis of gSG6 and fSG6 immunogenicity to humans suggests the occurrence of a wide cross-reactivity, even though the two proteins carry species-specific epitopes. This study supports the use of gSG6 as reliable indicator of exposure to the three main African malaria vectors, a marker which may be useful to monitor malaria transmission and evaluate vector control measures, especially in conditions of low malaria transmission and/or reduced vector density. The Anopheles stephensi SG6 protein also shares 80% identity with gSG6, suggesting the attractive possibility that the A. gambiae protein may also be useful to assess human exposure to several Asian malaria vectors.