bluuebunny/crossref_metadata_2025 huggingface dataset:
Increase in Rhamnolipid Synthesis under Iron-Limiting Conditions Influences Surface Motility and Biofilm Formation in
Pseudomonas aeruginosa
Authors: Glick Rivka , Gilmour Christie , Tremblay Julien , Satanower Shirley , Avidan Ofir , Déziel Eric , Greenberg E. Peter , Poole Keith , Banin Ehud
Published: February 2010

Iron is an essential element for life but also serves as an environmental signal for biofilm development in the opportunistic human pathogen
Pseudomonas aeruginosa
. Under iron-limiting conditions,
P. aeruginosa
displays enhanced twitching motility and forms flat unstructured biofilms. In this study, we present evidence suggesting that iron-regulated production of the biosurfactant rhamnolipid is important to facilitate the formation of flat unstructured biofilms. We show that under iron limitation the timing of rhamnolipid expression is shifted to the initial stages of biofilm formation (versus later in biofilm development under iron-replete conditions) and results in increased bacterial surface motility. In support of this observation, an
rhlAB
mutant defective in biosurfactant production showed less surface motility under iron-restricted conditions and developed structured biofilms similar to those developed by the wild type under iron-replete conditions. These results highlight the importance of biosurfactant production in determining the mature structure of
P. aeruginosa
biofilms under iron-limiting conditions.
Dual Control of
Sinorhizobium meliloti
RpoE2 Sigma Factor Activity by Two PhyR-Type Two-Component Response Regulators
Authors: Bastiat Bénédicte , Sauviac Laurent , Bruand Claude
Published: February 2010

RpoE2 is an extracytoplasmic function (ECF) sigma factor involved in the general stress response of
Sinorhizobium meliloti
, the nitrogen-fixing symbiont of the legume plant alfalfa. RpoE2 orthologues are widely found among alphaproteobacteria, where they play various roles in stress resistance and/or host colonization. In this paper, we report a genetic and biochemical investigation of the mechanisms of signal transduction leading to
S. meliloti
RpoE2 activation in response to stress. We showed that RpoE2 activity is negatively controlled by two paralogous anti-sigma factors, RsiA1 (SMc01505) and RsiA2 (SMc04884), and that RpoE2 activation by stress requires two redundant paralogous PhyR-type response regulators, RsiB1 (SMc01504) and RsiB2 (SMc00794). RsiB1 and RsiB2 do not act at the level of
rpoE2
transcription but instead interact with the anti-sigma factors, and we therefore propose that they act as anti-anti-sigma factors to relieve RpoE2 inhibition in response to stress. This model closely resembles a recently proposed model of activation of RpoE2-like sigma factors in
Methylobacterium extorquens
and
Bradyrhizobium japonicum
, but the existence of two pairs of anti- and anti-anti-sigma factors in
S. meliloti
adds an unexpected level of complexity, which may allow the regulatory system to integrate multiple stimuli.
17β-Estradiol modulates the macrophage migration inhibitory factor secretory pathway by regulating ABCA1 expression in human first-trimester placenta
Authors: Ietta Francesca , Bechi Nicoletta , Romagnoli Roberta , Bhattacharjee Jayonta , Realacci Massimo , Di Vito Maura , Ferretti Cristina , Paulesu Luana
Published: February 2010

Successful pregnancy involves a series of events, most of them mediated by hormones and cytokines. Estrogens, besides being important for placental growth and embryo development, have a marked effect on the immune system exerting either pro- or anti-inflammatory properties. Numerous studies suggest that estrogens directly affect cellular function, including cytokine production. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in pregnancy, particularly during the earlier stages of placentation. Since reports on mice have shown that estrogens modulate MIF, herein we investigated the effect of estrogens on human placental MIF. By using an in vitro model of first-trimester chorionic villous explants, we found that 17β-estradiol (E2) was able to modulate the release of MIF in a dose-dependent manner (10−12vs. 10−9M, P < 0.05; 10−9vs. 10−5M, P < 0.05; 10−12vs. 10−5M, P < 0.001). Unlike MIF release, no significant change in tissue MIF protein or MIF mRNA was observed. We showed evidence that E2concentrations (10−9and 10−5M) act on placental tissue downregulating the mRNA and protein expression of the ATP-binding cassette transporter protein A1, a membrane transporter involved in MIF secretion. These findings emphasize the mutual cooperation between hormones and cytokines and suggest that increasing estrogen levels with advancing gestation may have a major role in regulating placental MIF secretion.
Hydrogen sulfide protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis by preventing GSK-3β-dependent opening of mPTP
Authors: Yao Ling-Ling , Huang Xiao-Wei , Wang Yong-Gang , Cao Yin-Xiang , Zhang Cai-Cai , Zhu Yi-Chun
Published: February 2010

Hydrogen sulfide (H2S) is an endogenously generated gaseous transmitter, which has recently been suggested to regulate cardiovascular functions. The present study aims to clarify the mechanisms underlying the cardioprotective effects of H2S. Signaling elements were examined in cardiomyocytes cultured under hypoxia/reoxygenation conditions and in a rat model of ischemia-reperfusion. In cultured cardiomyocytes, sodium hydrosulfide (NaHS; 10, 30, and 50 μmol/l) showed concentration-dependent inhibitory effects on cardiomyocyte apoptosis induced by hypoxia/reoxygenation. These effects were associated with an increase in phosphorylation of glycogen synthase kinase-3β (GSK-3β) (Ser9) and a decrease in Bax translocation, caspase-3 activation, and mitochondrial permeability transition pore (mPTP) opening. Transfection of a phosphorylation-resistant mutant of GSK-3β at Ser9 attenuated the effects of NaHS in reducing cardiomyocyte apoptosis, Bax translocation, caspase-3 activation, and mPTP opening. In a rat model of ischemia-reperfusion, NaHS administration reduced myocardial infarct size and increased the phosphorylation of GSK-3β (Ser9) at a dose of 30 μmol/kg. In conclusion, the H2S donor prevents cardiomyocyte apoptosis by inducing phosphorylation of GSK-3β (Ser9) and subsequent inhibition of mPTP opening.
Strain-dependent susceptibility for hypertension in mice resides in the natural killer gene complex
Authors: Taherzadeh Zhila , VanBavel Ed , de Vos Judith , Matlung Hanke L. , van Montfrans Gert , Brewster Lizzy M. , Seghers Leonard , Quax Paul H. A. , Bakker Erik N. T. P.
Published: February 2010

Hypertension is associated with chronic vascular inflammation. We tested the hypothesis that the sensitivity to develop hypertension and vascular remodeling depends on the immunological background. Blood pressure, vascular remodeling, endothelial function, vascular architecture (number of collateral arteries), and expression of inflammatory cytokines were determined in mice that received NG-nitro-l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthesis. We studied C57BL/6, BALB/c, and BALB.B6-Cmv1r mice, a congenic strain where the natural killer (NK) gene complex of C57BL/6 mice is introduced in the BALB/c background. During a 4-wk treatment with l-NAME, blood pressure initially increased in both C57BL/6 and BALB/C mice, but after 4 wk, only C57BL/6 mice showed a significant increase in mean arterial blood pressure (+53 mmHg; P < 0.001) and small artery inward remodeling. Endothelial function and vascular design were significantly different between C57BL/6 mice and BALB/C mice. The inflammatory response was similar in C57BL/6 and BALB/C mice, except for the leukocyte marker CD11b. Cellular colocalization of CD11b with NK1.1 indicated the recruitment of NK cells in C57BL/6 mice. Congenic BALB.B6-Cmv1r mice showed the same endothelial response and vascular architecture as BALB/c mice. However, BALB.B6-Cmv1r mice displayed a similar sensitivity to hypertension and vascular remodeling as C57BL/6 mice. In conclusion, we have identified the NK gene complex as an important determinant in the genetically determined sensitivity to develop l-NAME-induced hypertension in mice.
Novel bradykinin signaling in adult rat cardiac myocytes through activation of p21-activated kinase
Authors: Ke Yunbo , Sheehan Katherine A. , Egom E. Eroume A. , Lei Ming , Solaro R. John
Published: February 2010

Although bradykinin (BK) is known to exert effects on the myocardium, its intracellular signaling pathways remain poorly understood. Experiments in other cell types indicated that p21-activated kinase-1 (Pak1), a Ser/Thr kinase downstream of small monomeric G proteins, is activated by BK. We previously reported that the expression of active Pak1 in adult cardiac myocytes induced activation of protein phosphatase 2A and dephosphorylation of myofilament proteins (Ke et al. Circ Res 94: 194–200, 2004). In experiments reported here, we tested the hypothesis that BK signals altered protein phosphorylation in adult rat cardiac myocytes through the activation and translocation of Pak1. Treatment of myocytes with BK resulted in the activation of Pak1 as demonstrated by increased autophosphorylation at Thr423 and a diminished striated localization, which is present in the basal state. BK induced dephosphorylation of both cardiac troponin I and phospholamban. Treatment of isolated myocytes with BK also blunted the effect of isoproterenol to enhance peak Ca2+and relaxation of Ca2+transients. Protein phosphatase 2A was demonstrated to associate with both Pak 1 and phospholamban. Our studies indicate a novel signaling mechanism for BK in adult rat cardiac myocytes and support our hypothesis that Pak 1 is a significant regulator of phosphatase activity in the heart.
Impact of anti-apoptotic and anti-oxidative effects of bone marrow mesenchymal stem cells with transient overexpression of heme oxygenase-1 on myocardial ischemia
Authors: Tsubokawa Toshinari , Yagi Kunimasa , Nakanishi Chiaki , Zuka Masahiko , Nohara Atsushi , Ino Hidekazu , Fujino Noboru , Konno Tetsuo , Kawashiri Masa-aki , Ishibashi-Ueda Hatsue , Nagaya Noritoshi , Yamagishi Masakazu
Published: February 2010

Although mesenchymal stem cells (MSCs) have therapeutic potential for tissue injury, intolerance and poor cell viability limit their reparative capability. Therefore, we examined the impact of bone marrow-derived MSCs, in which heme oxygenase-1 (HO-1) was transiently overexpressed, on the repair of an ischemic myocardial injury. When MSCs and HO-1-overexpressed MSCs (MSCHO-1) were exposed to serum deprivation/hypoxia or H2O2-induced oxidative stress, MSCHO-1 exhibited increased resistance to cell apoptosis compared with MSCs (17 ± 1 vs. 30 ± 2%, P < 0.05) and were markedly resistant to cell death (2 ± 1 vs. 32 ± 2%, P < 0.05). Under these conditions, vascular endothelial growth factor (VEGF) production was 2.1-fold greater in MSCHO-1 than in MSCs. Pretreatment of MSCs and MSCHO-1 with phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B (Akt) pathway inhibitors such as LY-294002 (50 μM) or wortmannin (100 nM) significantly decreased VEGF production. In a rat infarction model with MSCs or MSCHO-1 (5 × 106 ± 0.1 × 106 cells/rat) transplantation, the number of TdT-mediated dUTP nick end-labeling-positive cells was significantly lower in the MSCHO-1 group than in the MSC group (12.1 ± 1.0 cells/field vs. 26.5 ± 2.6, P < 0.05) on the 4th day after cell transplantation. On the 28th day, increased capillary density associated with decreased infarction size was observed in the MSCHO-1 group (1,415 ± 47/mm2 with 21.6 ± 2.3%) compared with those in the MSCs group (1,215 ± 43/mm2 with 28.2 ± 2.3%, P < 0.05), although infarction size relative to area at risk was not different in each group at 24 h after transplantation. These results demonstrate that MSCHO-1 exhibit markedly enhanced anti-apoptotic and anti-oxidative capabilities compared with MSCs, thus contributing to improved repair of ischemic myocardial injury through cell survival and VEGF production associated with the PI 3-kinase/Akt pathway.
Reactivity of mouse alveolar macrophages to cigarette smoke is strain dependent
Authors: Vecchio Daniela , Arezzini Beatrice , Pecorelli Alessandra , Valacchi Giuseppe , Martorana Piero A. , Gardi Concetta
Published: February 2010

Cigarette smoke (CS) is a main risk factor in chronic obstructive pulmonary disease (COPD), but only 20% of smokers develop COPD, suggesting genetic predisposition. Animal studies have shown that C57BL/6J mice are sensitive to CS and develop emphysema, whereas Institute of Cancer Research (ICR) mice are not. To investigate the potential factors responsible for the different susceptibility of ICR and C57BL/6J mice to CS, we evaluated in alveolar macrophages (AMs) isolated from these strains of mice the possible mechanisms involved in the inflammatory and oxidative responses induced by CS. Lactate dehydrogenase (LDH) release revealed that C57BL/6J AMs were more susceptible to CS extract (CSE) toxicity than ICR. Differences were observed in inflammatory and oxidative response after CSE exposure. Proinflammatory cytokines and matrix metalloproteinases (MMPs) were increased in C57BL/6J but not ICR AMs. Control C57BL/6J AMs showed a higher baseline production of reactive oxygen species (ROS) and H2O2with lower baseline levels of GSH, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase (GPX2). This was associated with reduced histone deacetylase-2 (HDAC2) expression, activation of NF-κB, and higher basal levels of TNF-α and IL-6. CSE induced a decrease in HDAC2 protein levels in both C57BL/6J and ICR AMs; however, the level of HDAC2 was significantly lower in C57BL/6 than in ICR AMs. Furthermore, CSE enhanced NF-κB-dependent cytokine release only in C57BL/6J AMs. We suggest that an imbalance in oxidative stress decreases HDAC2 levels and facilitates NF-κB binding, resulting in a proinflammatory response in C57BL/6J but not in ICR AMs. These results could contribute in understanding the different susceptibility to CS of these strains of mice.
Induction of human β-defensin-2 in pulmonary epithelial cells byLegionella pneumophila: involvement of TLR2 and TLR5, p38 MAPK, JNK, NF-κB, and AP-1
Authors: Scharf Stefanie , Hippenstiel Stefan , Flieger Antje , Suttorp Norbert , N'Guessan Philippe Dje
Published: February 2010

Legionella pneumophila is an important causative agent of severe pneumonia in humans. Human alveolar epithelium is an effective barrier for inhaled microorganisms and actively participates in the initiation of innate host defense. Induction of antimicrobial peptide human β-defensin-2 (hBD-2) by various stimuli in epithelial cells has been reported. However, the mechanisms by which bacterial infections enhance hBD-2 expression remain poorly understood. In this study, we investigated the effect of the pulmonary pathogen L. pneumophila on induction of hBD-2 in human pulmonary epithelial cells. Infection with L. pneumophila markedly increased hBD-2 production, and the response was attenuated in Toll-like receptor (TLR) 2 and TLR5 transient knockdown cells. Furthermore, pretreatment with SB-202190 (an inhibitor of p38 MAPK) and JNK II (an inhibitor of c-Jun NH2-terminal kinase), but not U0126 (an inhibitor of ERK), reduced L. pneumophila-induced hBD-2 release in A549 cells. L. pneumophila-induced hBD-2 liberation was mediated via recruitment of NF-κB and AP-1 to the hBD-2 gene promoter. Additionally, we showed that exo- and endogenous hBD-2 elicited a strong antimicrobial effect towards L. pneumophila. Together, these results suggest that L. pneumophila induces hBD-2 release in A549 cells, and the induction seems to be mediated through TLR2 and TLR5 as well as activation of p38 MAPK, JNK, NF-κB, and AP-1.
Exercise-induced immunosuppression: roles of reactive oxygen species and 5′-AMP-activated protein kinase dephosphorylation within immune cells
Authors: Moir Hannah , Hughes Michael G. , Potter Stephen , Sims Craig , Butcher Lee R. , Davies Nia A. , Verheggen Kenneth , Jones Kenneth P. , Thomas Andrew W. , Webb Richard
Published: February 2010

We previously proposed 5′-AMP-activated protein kinase (AMPK) dephosphorylation within immune cells as an intracellular mechanism linking exercise and immunosuppression. In this study, AMPK phosphorylation underwent transient (<1 h) decreases (53.8 ± 7.2% basal) immediately after exercise (45 min of cycling at 70% V̇o2max) in a cohort of 16 adult male participants. Similar effects were seen with running. However, because exercise-induced inactivation of AMPK was previously shown to occur in an AMP-independent manner, the means by which AMPK is inactivated in this context is not yet clear. To investigate the hypothesis that exercise-induced inactivation of AMPK is mediated via signaling mechanisms distinct from changes in cellular AMP-to-ATP ratios, reactive oxygen species (ROS) and intracellular Ca2+signaling were investigated in mononuclear cells before and after exercise and in cultured monocytic MM6 cells. In in vitro studies, treatment with an antioxidant (ascorbic acid, 4 h, 50 μM) decreased MM6 cell intracellular ROS levels (88.0 ± 5.2% basal) and induced dephosphorylation of AMPK (44.7 ± 17.6% basal). By analogy, the fact that exercise decreased mononuclear cell ROS content (32.8 ± 16.6% basal), possibly due to downregulation (43.4 ± 8.0% basal) of mRNA for NOX2, the catalytic subunit of the cytoplasmic ROS-generating enzyme NADPH oxidase, may provide an explanation for the AMPK-dephosphorylating effect of exercise. In contrast, exercise-induced Ca2+signaling events did not seem to be coupled to changes in AMPK activity. Thus we propose that the exercise-induced decreases in both intracellular ROS and AMPK phosphorylation seen in this study constitute evidence supporting a role for ROS in controlling AMPK, and hence immune function, in the context of exercise-induced immunosuppression.
Associations of Clinical Stroke Misclassification (‘Clinical-Imaging Dissociation’) in Acute Ischemic Stroke
Authors: Potter Gillian , Doubal Fergus , Jackson Caroline , Sudlow Cathie , Dennis Martin , Wardlaw Joanna
Published: February 2010

Background: Up to 20% of lacunar infarcts are clinically misdiagnosed as cortical infarcts and vice versa. The reasons for this discrepancy are unclear. We assessed clinical and imaging features which might explain this ‘clinical-imaging dissociation’ (C-ID). Methods: Patients with an acute stroke syndrome (cortical or lacunar) underwent magnetic resonance imaging including diffusion-weighted imaging (DWI). We recorded DWI-positive infarcts and proximity to cortex for small subcortical infarcts. We examined factors associated with C-ID. Results: 137 patients with a mild cortical or lacunar syndrome had an acute ischemic lesion on DWI. Of these, 21/93 (23%) with a cortical syndrome had an acute lacunar infarct and 7/44 (16%) with a lacunar syndrome had an acute cortical infarct. From 72 patients with an acute lacunar infarct on DWI, lesion proximity to cortex (odds ratio (OR) 14.5, 95% confidence interval (CI) 1.61–130.1), left hemisphere location (OR 8.95, 95% CI 1.23–64.99) and diabetes (OR 17.1, 95% CI 1.49–196.16) predicted C-ID. On multivariate analysis of all 137 patients, C-ID was associated with diabetes (OR 7.12, 95% CI 1.86–27.2). Conclusions: C-ID occurs in a fifth of patients with mild stroke. Lacunar infarcts lying close to cortex are more likely to cause cortical symptoms. Diabetes is associated with any clinical-imaging mismatch. Stroke misclassification which can arise with clinical classification alone should be minimized in research by verification with high-sensitivity imaging.
Physical Exercise in Patients with Severe Kidney Disease
Authors: Kosmadakis G.C. , Bevington A. , Smith A.C. , Clapp E.L. , Viana J.L. , Bishop N.C. , Feehally J.
Published: February 2010

Patients with advanced chronic kidney disease (CKD), especially those on long-term dialysis, often suffer from muscle wasting and excessive fatigue. It is known that inactivity, muscle wasting and reduced physical functioning are associated with increased mortality in CKD. Known causes include uraemic myopathy and neuropathy, inactivity, and anaemia. Exercise in patients receiving regular dialysis treatment for end-stage renal disease was first introduced 3 decades ago, but is still only offered in a minority of renal units around the world, despite a significant body of evidence to support its use. Work is needed to increase awareness of the potential benefits of increased physical activity for patients with advanced CKD. This review summarizes the mechanisms of exercise intolerance and debility in advanced CKD patients, the methods used for the estimation of functional capacity, the options currently available for exercise training, and their influence on the well-being of this group of patients.
Identification and Assessment of Plasma Lysozyme as a Putative Biomarker of Atherosclerosis
Authors: Abdul-Salam Vahitha B. , Ramrakha Punit , Krishnan Unni , Owen David R. , Shalhoub Joseph , Davies Alun H. , Tang Tjun Y. , Gillard Jonathan H. , Boyle Joseph J. , Wilkins Martin R. , Edwards Robert J.
Published: February 2010

Objective—

To identify a plasma biomarker of atheromatous disease.

Methods and Results—

Surface-enhanced laser desorption ionization–time-of-flight mass spectrometry was used to identify possible plasma protein biomarkers of atheromatous disease in patients presenting with chronic stable angina pectoris by comparing those with 3-vessel disease with those without any evidence of coronary artery disease. The level of a 14.7-kDa protein was elevated; this protein was isolated and identified as a lysozyme. Arterial plasma lysozyme levels, measured by immunoassay, confirmed this observation in separate cohorts of patients. The application of arterial plasma lysozyme levels to 197 patients with varying degrees of coronary artery disease, using a cutoff value of 1.5 μg/mL, was able to distinguish patients with 1 or more occluded coronary arteries, with 86% sensitivity and 93% specificity. Of 20 patients with carotid atheroma, 19 had increased arterial plasma levels. In contrast, C-reactive protein levels showed no association with disease severity. Venous lysozyme levels in patients with carotid atheroma were shown to decrease after intensive atorvastatin treatment.

Conclusion—

Raised plasma lysozyme levels may be a useful biomarker of atherosclerotic cardiovascular disease and response to therapy. Additional studies to investigate this are warranted.
Embryonic Stem Cell–Derived Endothelial Cells Engraft Into the Ischemic Hindlimb and Restore Perfusion
Authors: Huang Ngan F. , Niiyama Hiroshi , Peter Christoph , De Abhijit , Natkunam Yasodha , Fleissner Felix , Li Zongjin , Rollins Mark D. , Wu Joseph C. , Gambhir Sanjiv S. , Cooke John P.
Published: February 2010

Objective—

We examined the effect of delivery modality on the survival, localization, and functional effects of exogenously administered embryonic stem cells (ESCs) or endothelial cells derived from them (ESC-ECs) in the ischemic hindlimb.

Methods and Results—

Murine ESCs or ESC-ECs were stably transduced with a construct for bioluminescence imaging (BLI) and fluorescent detection. In a syngeneic murine model of limb ischemia, ESCs or ESC-ECs were delivered by intramuscular (IM), intrafemoral artery (IA), or intrafemoral vein injections (n=5 in each group). For 2 weeks, cell survival and localization were tracked by BLI and confirmed by immunohistochemistry, and functional improvement was assessed by laser Doppler perfusion. BLI showed that ESCs localized to the ischemic limb after IM or IA, but not after intrafemoral vein administration. Regardless of the route of administration, ESCs were detected outside the hindlimb circulation in the spleen or lungs. ESCs did not improve limb perfusion and generated teratomas. In contrast, ESC-ECs delivered by all 3 modalities localized to the ischemic limb, as assessed by BLI. Most surprisingly, ESC-EC injected intrafemoral vein eventually localized to the ischemic limb after initially lodging in the pulmonary circulation. Immunohistochemical studies confirmed the engraftment of ESC-ECs into the limb vasculature after 2 weeks. Notably, ESC-ECs were not detected in the spleen or lungs after 2 weeks, regardless of route of administration. Furthermore, ESC-ECs significantly improved limb perfusion and neovascularization compared with the parental ESCs or the vehicle control group.

Conclusion—

In contrast to parental ESCs, ESC-ECs preferentially localized in the ischemic hindlimb by IA, IM, and intrafemoral vein delivery. ESC-ECs engrafted into the ischemic microvasculature, enhanced neovascularization, and improved limb perfusion.
Lung Endothelial Dysfunction in Congestive Heart Failure
Authors: Kerem Alexander , Yin Jun , Kaestle Stephanie M. , Hoffmann Julia , Schoene Axel M. , Singh Baljit , Kuppe Hermann , Borst Mathias M. , Kuebler Wolfgang M.
Published: February 2010

Rationale
:

Congestive heart failure (CHF) frequently results in remodeling and increased tone of pulmonary resistance vessels. This adaptive response, which aggravates pulmonary hypertension and thus, promotes right ventricular failure, has been attributed to lung endothelial dysfunction.

Objective
:

We applied real-time fluorescence imaging to identify endothelial dysfunction and underlying molecular mechanisms in an experimental model of CHF induced by supracoronary aortic banding in rats.

Methods and Results
:

Endothelial dysfunction was evident in lungs of CHF rats as impaired endothelium-dependent vasodilation and lack of endothelial NO synthesis in response to mechanical stress, acetylcholine, or histamine. This effect was not attributable to downregulation of endothelial NO synthase. Imaging of the cytosolic Ca
2+
concentration ([Ca
2+
]
i
) revealed a singular impairment of endothelial [Ca
2+
]
i
homeostasis and signaling characterized by a lack of [Ca
2+
]
i
oscillations and deficient or attenuated [Ca
2+
]
i
responses to mechanical stress, histamine, acetylcholine, or thapsigargin. Reconstitution of a [Ca
2+
]
i
signal by ionophore treatment restored endothelial NO production, but lack of endothelial responsiveness was not primarily attributable to downregulation of Ca
2+
influx channels in CHF. Rather, we identified a massive remodeling of the endothelial cytoskeleton in the form of an increased expression of β-actin and F-actin formation which contributed critically to endothelial dysfunction in CHF because cytoskeletal disruption by cytochalasin D largely reconstituted endothelial [Ca
2+
]
i
signaling and NO production.

Conclusions
:

Our findings characterize a unique scenario of endothelial dysfunction in CHF that is caused by a singular impairment of [Ca
2+
]
i
signaling, and identify cytoskeletal reorganization as a major regulator of endothelial signaling and function.
Short Communication: Dating Components of Human Atherosclerotic Plaques
Authors: Gonçalves Isabel , Stenström Kristina , Skog Göran , Mattsson Sören , Nitulescu Mihaela , Nilsson Jan
Published: February 2010

Rationale
:

Atherosclerotic plaques that give rise to acute clinical symptoms are typically characterized by degradation of the connective tissue and plaque rupture. Experimental studies have shown that mechanisms to repair vulnerable lesions exist, but the rate of remodeling of human plaque tissue has not been studied.

Objective
:

In the present study, we determined the biological age of different components of advanced human atherosclerotic plaques by analyzing tissue levels of
14
C released into the atmosphere during the nuclear weapons tests in the late 1950s and early 1960s.

Methods and Results
:

Atherosclerotic plaques were obtained from 10 patients (age 46 to 80 years) undergoing carotid surgery. Different regions of the plaques were dissected and analyzed for
14
C content using accelerator mass spectrometry. At the time of surgery, the mean biological age of the cap region was 6.4±3.2 years, which was significantly lower than that of the shoulder region (12.9±3.0 years,
P
<0.01), the interface toward the media (12.4±3.3 years,
P
<0.01), and the core (9.8±4.5 years,
P
<0.05). Analysis of proliferative activity and rate of apoptosis showed no signs of increased cellular turnover in the cap, suggesting that the lower
14
C content reflected a more recent time of formation.

Conclusions
:

These results show that the turnover time of human plaque tissue is very long and may explain why regression of atherosclerotic plaque size rarely is observed in cardiovascular intervention trials.
Clinical Spectrum of CADASIL and the Effect of Cardiovascular Risk Factors on Phenotype
Authors: Adib-Samii Poneh , Brice Glen , Martin Roswell J. , Markus Hugh S.
Published: February 2010

Background and Purpose—

Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is an inherited arteriopathy with clinical features that include recurrent lacunar stroke, migraine, and cognitive impairment. For reasons that remain unclear, there is great variability in the clinical expression of CADASIL, both between and within families. This study examined the clinical phenotype as well as any associations with risk factors and genotype in a large, prospective cohort.

Methods—

Two hundred symptomatic individuals from 124 families were recruited as part of a UK prevalence study of CADASIL and were seen subsequently in a national referral clinic. All were assessed by a standardized questionnaire and examination.

Results—

Mean age at assessment was 47.7 years and was 33.6 years at symptom onset. Migraine, usually with aura, was the most prevalent feature, affecting 75% of individuals. More than half had a history of stroke, with a mean age at onset of 46 years. Hypertension (odds ratio=2.57,
P
=0.007) and pack-years of smoking (odds ratio=1.07,
P
=0.001) were associated with an increased risk of stroke. A history of stroke was a significant risk factor for both dementia and disability. Mutations clustered in exon 4 of the
NOTCH3
gene, which contained ≥71.4% of familial mutations. Four previously unreported mutations were found (T697C, C1279T, G1370C, and C1774T). No associations were identified between genotype and clinical phenotype.

Conclusions—

Our data suggest that cardiovascular risk factors may modulate the clinical expression of CADASIL. The associations with hypertension and smoking suggest that risk factors should be treated aggressively in patients with CADASIL.
Statewide Hospital-Based Stroke Services in North Carolina
Authors: Goldstein Larry B.
Published: February 2010

Background and Purpose—

Statewide assessments of stroke prevention and treatment services were performed in North Carolina in 1998 and 2003. The 2003 survey found certain technologies, but not stroke-related programs, were more widely available. The survey was repeated in 2008 to determine whether there was an interval change in accessibility.

Methods—

A 2-page questionnaire was sent to each North Carolina hospital. Results were compared with the 1998 and 2003 surveys.

Results—

Complete responses were obtained from each of the state’s emergent stroke care hospitals. The proportions providing CT angiography and diffusion-weighted MRI increased between each period (each
P
<0.05); the use of care maps and intravenous tissue plasminogen activator protocols increased between 2003 and 2008 but not between 1998 and 2003. There were no changes in availability of MRI, MR angiography, catheter angiography, carotid ultrasound, transcranial Doppler, transthoracic echocardiography, or in the proportions of hospitals having a stroke unit, having a neurologist or neurointerventionalist readily available, or providing stroke-related public education (each
P
>0.05). The proportions of hospitals having a group of “basic” stroke capabilities did not change (18%, 21%, and 20%, respectively,
P
>0.05). In 2008, 41% of North Carolina’s population resided in a county with at least 1 Primary Stroke Center and an additional 40% in a county using telemedicine or having a transfer plan for patients with acute stroke.

Conclusions—

The availability of certain diagnostic tests, but not specialty staff or stroke units, increased in North Carolina hospitals between 1998 and 2008. Although there was no change in stroke-related hospital-based organizational features between 1998 and 2003, there were improvements between 2003 and 2008, possibly reflecting programs aimed at developing stroke care systems.
Acupuncture in Poststroke Rehabilitation
Authors: Wu Ping , Mills Edward , Moher David , Seely Dugald
Published: February 2010

Background and Purpose—

Acupuncture is a low-risk treatment with purported claims of effectiveness for poststroke rehabilitation. To comprehensively assess the efficacy of acupuncture in poststroke rehabilitation, we conducted a systematic review and meta-analysis of all randomized clinical trials of acupuncture for poststroke rehabilitation.

Methods—

We searched 7 English and 2 Chinese databases from inception to September 2009. Eligible studies included randomized clinical trials that evaluated the clinical efficacy of acupuncture in adult patients with disability after stroke. We extracted data on trial quality, protocol, and outcomes assessed. A summary OR was calculated based on pooled dichotomous results. I
2
was used to infer heterogeneity and we conducted metaregression to determine if specific covariates explained heterogeneity.

Results—

Thirty-five articles written in Chinese and 21 articles written in English were included. The overall quality of the studies was “fair” and most studies were small (median n=86; range, 16 to 241). The majority (80%) of the studies reported a significant benefit from acupuncture; however, there was some evidence of publication bias. In 38 trials, data were available for meta-analysis and metaregression, yielding an OR in favor of acupuncture compared with controls (OR=4.33, 95% CI: 3.09 to 6.08; I
2
=72.4%). Randomization, modes of delivery, method of control, study source country, and reporting of randomization may explain some of the heterogeneity observed between the studies.

Conclusions—

Randomized clinical trials demonstrate that acupuncture may be effective in the treatment of poststroke rehabilitation. Poor study quality and the possibility of publication bias hinder the strength of this recommendation and argue for a large, transparent, well-conducted randomized clinical trial to support this claim and implement changes to clinical practice.
Inelastic Interface Damage Modeling with Friction Effects: Application to Z-Pinning Reinforcement in Carbon Fiber Epoxy Matrix Laminates
Authors: Gornet Laurent , Ijaz Hassan , Cartié Denis D.R.
Published: February 2010

This article presents the implementation of a new inelastic damage model able to carry out simulation of initiation and evolution of damage in the Z-pinned laminated composite structures with friction effects. The classical elastic damage model is modified to an inelastic model with friction effects obeying the simple Coulomb friction criterion. The main idea is the modification of strain energy parameter by introducing sliding and friction parameters. The simulations of single Z-fiber pull tests highlight the effectiveness of the proposed model for micro-scale predictions.
Fibril Morphology and Tendon Mechanical Properties in Patellar Tendinopathy
Authors: Kongsgaard Mads , Qvortrup Klaus , Larsen Jytte , Aagaard Per , Doessing Simon , Hansen Philip , Kjaer Michael , Magnusson S. Peter
Published: February 2010

Background

Patellar tendinopathy is characterized by pathologic abnormalities. Heavy slow resistance training (HSR) is effective in the management of patellar tendinopathy, but the underlying functional mechanisms remain elusive.

Purpose

To investigate fibril morphology and mechanical properties in patellar tendinopathy and the effect of HSR on these properties.

Study Design

Cohort study; Level of evidence, 2.

Methods

Eight male patients with patellar tendinopathy completed 12 weeks of HSR. Nine healthy subjects served as controls. Assessments were conducted at baseline and at 12 weeks. Patients assessed symptoms/function and maximal tendon pain during activity. Tendon biopsy samples were analyzed for fibril density, volume fraction, and mean fibril area. Tendon mechanical properties were assessed using force and ultrasonography samplings.

Results

Patients improved in symptoms/function (P = .02) and maximal tendon pain during activity (P = .008). Stiffness and modulus of control and tendinopathy tendons were similar at baseline. Stiffness remained unaffected in control tendons (3487 ± 392 to 3157 ± 327 N/mm, P = .57) but declined in tendinopathic tendons at 12 weeks (3185 ± 187 to 2701 ± 201 N/mm, P = .04). At baseline, fibril volume fraction was equal, fibril density smaller (P = .03), and mean fibril area tended to be higher in tendinopathy versus controls (P = .07). Fibril morphology remained unchanged in controls but fibril density increased (70% ± 18%, P = .02) and fibril mean area decreased (—26% ± 21%, P = .04) in tendinopathic tendons after HSR.

Conclusion

Fibril morphology is abnormal in tendinopathy, but tendon mechanical properties are not. Clinical improvements after HSR were associated with changes in fibril morphology toward normal fibril density and mean fibril area. Heavy slow resistance training improved the clinical outcome of patellar tendinopathy, and these improvements were associated with normalization of fibril morphology, most likely due to a production of new fibrils.
Using Systematic Screening Data to Assess Risk and Identify Students for Targeted Supports: Illustrations Across the K-12 Continuum
Authors: Lane Kathleen Lynne , Kalberg Jemma Robertson , Menzies Holly , Bruhn Allison , Eisner Shanna , Crnobori Mary
Published: February 2010

In this article the authors provide practitioners and researchers with three illustrations of how to use systematic screening tools within the context of three-tiered models of support to (a) measure the overall level of risk present in a school over time and (b) identify students who may require more targeted supports in the form of secondary and tertiary prevention efforts. Specifically, the authors explore data-driven approaches to interpreting systematic screening data collected as part of regular school practices at the high, middle, and elementary school levels. In each illustration they describe the student population, the procedures used by each school to construct the three-tiered model, the primary prevention plan developed, the systematic screening tool incorporated into regular school practices, and the data analysis plan. Furthermore, the authors offer findings of treatment outcome studies that demonstrate how student risk shifts over time following program implementation. They also include hypothetical and actual illustrations of how to use data from a variety of screening tools to identify students for secondary and tertiary prevention efforts.
The Influence of Fidelity of Implementation on the Reading Outcomes of Middle School Students Experiencing Reading Difficulties
Authors: Benner Gregory J. , Nelson J. Ron , Stage Scott A. , Ralston Nicole C.
Published: February 2010

The purpose of this study is to examine the extent to which two specific elements of fidelity of implementation (i.e., adherence and quality of delivery) enhanced or constrained the effects of a reading intervention for middle school students experiencing reading difficulties. A total of 281 middle school students with reading difficulties received an intensive reading intervention (i.e., Corrective Reading Decoding strand) delivered by trained school staff ( n = 21) at three middle schools. Although students receiving the Corrective Reading Decoding strand made statistically significant ( p < .001) improvements in their basic reading skills and passage comprehension overall, variations in student gains were found. Overall fidelity of implementation accounted for 22% and 18% of the variance in the gains in basic reading skills and passage comprehension of middle school students with reading difficulties, respectively ( p < .05). Two teacher actions, following the lesson format as designed and reteaching lessons when needed, predicted student basic reading and passage comprehension skills above and beyond other teacher actions ( p < .05). Results, implications, and limitations are discussed.
Doing the Right Thing With Families During Critical Life Events
Authors: Milton Constance L.
Published: February 2010

With complex medical technology readily available for life-sustaining situations, making critical healthcare decisions has never been more arduous. Individuals, families, and communities face difficult circumstances, while all-at-once attempting to make decisions that are ethically considered to be doing the right thing. What should the nurse do and how ought the nurse be with others during these moments of potentially divisive situations for families. This article begins a discussion of the ethical complexities for doing what is right in the midst of critical life events through the lens of the humanbecoming family model.
A Meta-Analysis of Self-Care Behavior Research on Elders in Thailand
Authors: Klainin Piyanee , Ounnapiruk Liwan
Published: February 2010

Self-care is essential for elderly individuals to maintain their optimal level of health. This meta-analysis was conducted to summarize research findings relating to self-care among the elderly in Thailand. Twenty studies undertaken from 1990 to 2008 were used and 328 effect sizes were computed. Most studies were unpublished master’s theses guided by Orem’s self-care deficit theory. Data were collected in these studies by face-to-face interviews. Variables with the largest effect sizes encompassed self-concept, social support, and self-efficacy. Those with medium effect sizes entailed family relationships, overall health beliefs, internal locus of control, health status, and external locus of control. Results from this meta-analysis is useful information for nursing.
Experimental impact of aspirin exposure on rat intestinal bacteria, epithelial cells and cell line
Authors: Upreti Raj K , Kannan A. , Pant AB
Published: February 2010

Aspirin, a commonly used therapeutic non-steroidal anti-inflammatory drug (NSAID) is known to cause gastric mucosal damage. Intestinal bacteria having a regulatory effect on intestinal homeostasis play significant role in NSAID-induced intestinal injury. Bacteria and specific cell lines are considered to be suitable for toxicity screening and testing of chemicals. Therefore, to evaluate and compare in vitro toxicity, cultures of rat intestinal epithelial cells (IEC), isolated bacteria and IEC-6 cell line were assessed for viability, morphometric analysis, membrane transport enzymes and structural constituents for membrane damage, dehydrogenase activity test for respiratory and energy producing processes and esterase activity test for intra- and extra-cellular degradation, following the post exposure to aspirin (0—50 µg mL- 1). Similar pattern of dose-dependent changes in these parameters were observed in three types of cells. Similar in situ effects on IEC validated the in vitro findings. These findings indicate that higher aspirin concentrations may alter cellular functions of IEC and gut bacteria. Furthermore, results suggest that gut bacteria and IEC-6 cell line can be used for the initial screening of gastrointestinal cellular toxicity caused by NSAIDs.
Retinoic acid-inducible gene-I (RIG-I) is induced by IFN-γ in human mesangial cells in culture: possible involvement of RIG-I in the inflammation in lupus nephritis
Authors: Imaizumi T. , Tanaka H. , Tajima A. , Tsuruga K. , Oki E. , Sashinami H. , Matsumiya T. , Yoshida H. , Inoue I. , Ito E.
Published: February 2010

Interferon-γ is a potent Th1-type cytokine and a key molecule in the pathogenesis of autoimmune diseases including lupus nephritis. Retinoic acid-inducible gene-I is a putative RNA helicase that plays an important role in immune and inflammatory reactions. We previously demonstrated the increased expression of the retinoic acid-inducible gene-I protein in the kidney tissue of patients with lupus nephritis, and the presence of a significant amount of retinoic acid-inducible gene-I mRNA in the urinary sediment of patients with this inflammatory renal disease. In the present study, interferon-γ was found to induce the expression of retinoic acid-inducible gene-I in human mesangial cells in culture. Knockdown of retinoic acid-inducible gene-I inhibited the interferon-γ-induced upregulation of interferon regulatory factor 7, a transcriptional factor involved in immune and inflammatory reactions. These findings suggest that retinoic acid-inducible gene-I produced by mesangial cells may be involved in the pathogenesis of lupus nephritis.
The Generational Rivalry for Time
Authors: King Vera
Published: February 2010

This article examines the effects of acceleration on the dynamic of time and power in generational relationships. The cultural patterns of an accelerated, hyperflexible life conduct in late modernity, it is argued, encourage a form of generational relationship characterized chiefly by the generational rivalry for time. In place of a steadfast ‘gift of time’ to younger generations appear various forms of the ‘annexation of time’. Insofar, late modernity is distinguished by a generative paradox: while there is increased demand for the intensity of generational ties and the quality of generational relationships and while accelerated societies necessitate greater capacities for coping with more complex lives and the respective conditions of growing up, the preconditions for this in generational relationships have nevertheless become more precarious in a variety of ways.
Using Focus Groups in Community-Based Participatory Research: Challenges and Resolutions
Authors: Makosky Daley Christine , James Aimee S. , Ulrey Ezekiel , Joseph Stephanie , Talawyma Angelia , Choi Won S. , Greiner K. Allen , Coe M. Kathryn
Published: February 2010

A community-based participatory approach requires that community members be involved in all phases of the research process. We describe three focus group studies with American Indians in Kansas and Missouri, using a newly developed method of conducting and analyzing focus groups with community input (72 focus groups, 519 participants). We conducted two needs assessment studies focused on barriers to breast and colorectal cancer screening and one study focused on Internet use for gathering health information. Community members and researchers collaborated to develop guides for the focus group moderators. Community organizations and our community advisory board conducted recruitment, and we trained and employed community members as moderators, assistant moderators, and analysts. Our community partners also helped with dissemination of research findings to their constituents. The methodologic approach and data from these three studies will allow us to more appropriately address health disparities in the American Indian community, with full community support for our research.