bluuebunny/crossref_metadata_2025 huggingface dataset:
Ancient Asteroids Enriched in Refractory Inclusions
Authors: Sunshine J. M. , Connolly H. C. , McCoy T. J. , Bus S. J. , La Croix L. M.
Published: March 2008

Calcium- and aluminum-rich inclusions (CAIs) occur in all classes of chondritic meteorites and contain refractory minerals predicted to be the first condensates from the solar nebula. Near-infrared spectra of CAIs have strong 2-micrometer absorptions, attributed to iron oxide–bearing aluminous spinel. Similar absorptions are present in the telescopic spectra of several asteroids; modeling indicates that these contain ∼30 ± 10% CAIs (two to three times that of any meteorite). Survival of these undifferentiated, large (50- to 100-kilometer diameter) CAI-rich bodies suggests that they may have formed before the injection of radiogenic
26
Al into the solar system. They have also experienced only modest post-accretionary alteration. Thus, these asteroids have higher concentrations of CAI material, appear less altered, and are more ancient than any known sample in our meteorite collection, making them prime candidates for sample return.
High-Thermoelectric Performance of Nanostructured Bismuth Antimony Telluride Bulk Alloys
Authors: Poudel Bed , Hao Qing , Ma Yi , Lan Yucheng , Minnich Austin , Yu Bo , Yan Xiao , Wang Dezhi , Muto Andrew , Vashaee Daryoosh , Chen Xiaoyuan , Liu Junming , Dresselhaus Mildred S. , Chen Gang , Ren Zhifeng
Published: March 2008

The dimensionless thermoelectric figure of merit (ZT) in bismuth antimony telluride (BiSbTe) bulk alloys has remained around 1 for more than 50 years. We show that a peak ZT of 1.4 at 100°C can be achieved in a p-type nanocrystalline BiSbTe bulk alloy. These nanocrystalline bulk materials were made by hot pressing nanopowders that were ball-milled from crystalline ingots under inert conditions. Electrical transport measurements, coupled with microstructure studies and modeling, show that the ZT improvement is the result of low thermal conductivity caused by the increased phonon scattering by grain boundaries and defects. More importantly, ZT is about 1.2 at room temperature and 0.8 at 250°C, which makes these materials useful for cooling and power generation. Cooling devices that use these materials have produced high-temperature differences of 86°, 106°, and 119°C with hot-side temperatures set at 50°, 100°, and 150°C, respectively. This discovery sets the stage for use of a new nanocomposite approach in developing high-performance low-cost bulk thermoelectric materials.
Gastric relaxation induced by hyperglycemia is mediated by vagal afferent pathways in the rat
Authors: Zhou Shi-Yi , Lu Yuan-Xu , Owyang Chung
Published: March 2008

Hyperglycemia has a profound effect on gastric motility. However, little is known about the site and mechanism that sense alteration in blood glucose level. The identification of glucose-sensing neurons in the nodose ganglia led us to hypothesize that hyperglycemia acts through vagal afferent pathways to inhibit gastric motility. With the use of a glucose-clamp rat model, we showed that glucose decreased intragastric pressure in a dose-dependent manner. In contrast to intravenous infusion of glucose, intracisternal injection of glucose at 250 and 500 mg/dl had little effect on intragastric pressure. Pretreatment with hexamethonium, as well as truncal vagotomy, abolished the gastric motor responses to hyperglycemia (250 mg/dl), and perivagal and gastroduodenal applications of capsaicin significantly reduced the gastric responses to hyperglycemia. In contrast, hyperglycemia had no effect on the gastric contraction induced by electrical field stimulation or carbachol (10−5 M). To rule out involvement of serotonergic pathways, we showed that neither granisetron (5-HT3 antagonist, 0.5 g/kg) nor pharmacological depletion of 5-HT using p-chlorophenylalanine (5-HT synthesis inhibitor) affected gastric relaxation induced by hyperglycemia. Lastly, NG-nitro-l-arginine methyl ester (l-NAME) and a VIP antagonist each partially reduced gastric relaxation induced by hyperglycemia and, in combination, completely abolished gastric responses. In conclusion, hyperglycemia inhibits gastric motility through a capsaicin-sensitive vagal afferent pathway originating from the gastroduodenal mucosa. Hyperglycemia stimulates vagal afferents, which, in turn, activate vagal efferent cholinergic pathways synapsing with intragastric nitric oxide- and VIP-containing neurons to mediate gastric relaxation.
A cholesterol-free, high-fat diet suppresses gene expression of cholesterol transporters in murine small intestine
Authors: de Vogel-van den Bosch Heleen M. , de Wit Nicole J. W. , Hooiveld Guido J. E. J. , Vermeulen Hanneke , van der Veen Jelske N. , Houten Sander M. , Kuipers Folkert , Müller Michael , van der Meer Roelof
Published: March 2008

Transporters present in the epithelium of the small intestine determine the efficiency by which dietary and biliary cholesterol are taken up into the body and thus control whole-body cholesterol balance. Niemann-Pick C1 Like Protein 1 (Npc1l1) transports cholesterol into the enterocyte, whereas ATP-binding cassette transporters Abca1 and Abcg5/Abcg8 are presumed to be involved in cholesterol efflux from the enterocyte toward plasma HDL and back into the intestinal lumen, respectively. Abca1, Abcg5, and Abcg8 are well-established liver X receptor (LXR) target genes. We examined the effects of a high-fat diet on expression and function of cholesterol transporters in the small intestine in mice. Npc1l1, Abca1, Abcg5, and Abcg8 were all downregulated after 2, 4, and 8 wk on a cholesterol-free, high-fat diet. The high-fat diet did not affect biliary cholesterol secretion but diminished fractional cholesterol absorption from 61 to 42% ( P < 0.05). In an acute experiment in which triacylglycerols of unsaturated fatty acids were given by gavage, we found that this downregulation occurs within a 6-h time frame. Studies in LXRα-null mice, confirmed by in vitro data, showed that fatty acid-induced downregulation of cholesterol transporters is LXRα independent and associated with a posttranslational increase in 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity that reflects induction of cholesterol biosynthesis as well as with a doubling of neutral fecal sterol loss. This study highlights the induction of adaptive changes in small intestinal cholesterol metabolism during exposure to dietary fat.
CCK-induced pancreatic growth is not limited by mitogenic capacity in mice
Authors: Crozier Stephen J. , Sans Maria Dolors , Lang Charles H. , D'Alecy Louis G. , Ernst Stephen A. , Williams John A.
Published: March 2008

In mice fed trypsin inhibitor (camostat) to elevate endogenous CCK, pancreatic growth plateaus by 7 days. It is unknown whether this represents the maximum growth capacity of the pancreas. To test the ability of CCK to drive further growth, mice were fed chow containing camostat (0.1%) for 1 wk, then fed standard chow for 1 wk, and finally returned to the camostat diet for a week. Pancreatic mass increased to 245% of initial value (iv) following 1 wk of camostat feeding, decreased to 147% iv following a 1 wk return to normal chow, and increased to 257% iv with subsequent camostat feeding. Camostat feeding was associated with significant increases in circulating CCK and changes in pancreatic mass were paralleled by changes in protein and DNA content. Moreover, regression of the pancreas following camostat feeding was associated with changes in the expression of the autophagosome marker LC3. Pancreatic protein synthetic rates were 130% of control after 2 days on camostat but were equivalent to control after 7 days. Changes in the phosphorylation of 4E-BP1 and S6, downstream effectors of mammalian target of rapamycin (mTOR), paralleled changes in protein synthetic rates. Cellular content of Akt, an upstream activating kinase of mTOR, decreased after 7 days of camostat feeding whereas expression of the E3 ubiquitin-ligases and the cell cycle inhibitor p21 increased after 2 days. These results indicate that CCK-stimulated growth of the pancreas is not limited by acinar cell mitogenic capacity but is due, at least in part, to inhibition of promitogenic Akt signaling.
EnteropathogenicE. coli-induced barrier function alteration is not a consequence of host cell apoptosis
Authors: Viswanathan V. K. , Weflen Andrew , Koutsouris Athanasia , Roxas Jennifer L. , Hecht Gail
Published: March 2008

Enteropathogenic Escherichia coli (EPEC) is a diarrheagenic pathogen that perturbs intestinal epithelial function. Many of the alterations in the host cells are mediated by effector molecules that are secreted directly into epithelial cells by the EPEC type III secretion system. The secreted effector molecule EspF plays a key role in redistributing tight junction proteins and altering epithelial barrier function. EspF has also been shown to localize to mitochondria and trigger membrane depolarization and eventual host cell death. The relationship, if any, between EspF-induced host cell death and epithelial barrier disruption is presently not known. Site-directed mutation of leucine 16 (L16E) of EspF impairs both mitochondrial localization and consequent host cell death. Although the mutation lies within a region critical for type III secretion, EspF(L16E) is secreted efficiently from EPEC. Despite its inability to promote cell death, EspF(L16E) was not impaired for tight junction alteration or barrier disruption. Consistent with this, the pan-caspase inhibitor Q-VD-OPH, despite reducing EPEC-induced host cell death, had no effect on infection-mediated barrier function alteration. Thus EPEC alters the epithelial barrier independent of its ability to induce host cell death.
Angiotensin-(1-12) is an alternate substrate for angiotensin peptide production in the heart
Authors: Trask Aaron J. , Jessup Jewell A. , Chappell Mark C. , Ferrario Carlos M.
Published: March 2008

Identification of angiotensin-(1-12) as an intermediate precursor derived directly from angiotensinogen led us to explore whether the heart has the capacity to process angiotensin-(1-12) into biologically active angiotensin peptides. The generation of angiotensin I, angiotensin II, and angiotensin-(1-7) from exogenous angiotensin-(1-12) was evaluated in the effluent of isolated perfused hearts mounted on a Langendorff apparatus in three normotensive and two hypertensive strains: Sprague-Dawley, Lewis, congenic mRen2.Lewis, Wistar-Kyoto, and spontaneously hypertensive rats. Hearts were perfused with Krebs solution for 60 min before and after the addition of angiotensin-(1-12) (10 nmol/l). Angiotensin-(1-12) caused the rapid appearance of both angiotensin I and angiotensin II in the perfusate that peaked between 30 and 60 min of recirculation. Production of angiotensin-(1-7) from exogenous angiotensin-(1-12) rose steadily over the course of the 60-min experiment. These data directly demonstrate that angiotensin-(1-12) is a substrate for the formation of angiotensin peptides in cardiac tissue. This finding further suggests that this angiotensinogen-derived product is a previously unrecognized important precursor peptide to the renin-angiotensin system cascade.
Reduced effects of BAY K 8644 on L-type Ca2+ current in failing human cardiac myocytes are related to abnormal adrenergic regulation
Authors: Chen Xiongwen , Zhang Xiaoying , Harris David M. , Piacentino Valentino , Berretta Remus M. , Margulies Kenneth B. , Houser Steven R.
Published: March 2008

Abnormal L-type Ca2+ channel (LTCC, also named Cav1.2) density and regulation are important contributors to depressed contractility in failing hearts. The LTCC agonist BAY K 8644 (BAY K) has reduced inotropic effects on failing myocardium. We hypothesized that BAY K effects on the LTCC current ( ICaL) in failing myocytes would be reduced because of increased basal activity. Since support of the failing heart with a left ventricular assist device (LVAD) improves contractility and adrenergic responses, we further hypothesized that BAY K effects on ICaL would be restored in LVAD-supported failing hearts. We tested our hypotheses in human ventricular myocytes (HVMs) isolated from nonfailing (NF), failing (F), and LVAD-supported failing hearts. We found that 1) BAY K had smaller effects on ICaL in F HVMs compared with NF HVMs; 2) BAY K had diminished effects on ICaL in NF HVM pretreated with isoproterenol (Iso) or dibutyryl cyclic AMP (DBcAMP); 3) BAY K effects on ICaL in F HVMs pretreated with acetylcholine (ACh) were normalized; 4) Iso had no effect on NF HVMs pretreated with BAY K; 5) BAY K effects on ICaL in LVAD HVMs were similar to those in NF HVMs; 6) BAY K effects were reduced in LVAD HVMs pretreated with Iso or DBcAMP; 7) Iso had no effect on ICaL in LVAD HVMs pretreated with BAY K. Collectively, these results suggest that the decreased BAY K effects on LTCC in F HVMs are caused by increased basal channel activity, which should contribute to abnormal contractility reserve.
Inhalation of sphingosine kinase inhibitor attenuates airway inflammation in asthmatic mouse model
Authors: Nishiuma Teruaki , Nishimura Yoshihiro , Okada Taro , Kuramoto Emi , Kotani Yoshikazu , Jahangeer Saleem , Nakamura Shun-ichi
Published: March 2008

Sphingosine 1-phosphate (S1P) produced by sphingosine kinase (SPHK) is implicated in acute immunoresponses, however, mechanisms of SPHK/S1P signaling in the pathogenesis of bronchial asthma are poorly understood. In this study, we hypothesized that SPHK inhibition could ameliorate lung inflammation in ovalbumin (OVA)-challenged mouse lungs. Six- to eight-week-old C57BL/6J mice were sensitized and exposed to OVA for 3 consecutive days. Twenty-four hours later, mice lungs and bronchoalveolar lavage (BAL) fluid were analyzed. For an inhibitory effect, either of the two different SPHK inhibitors, N, N-dimethylsphingosine (DMS) or SPHK inhibitor [SK-I; 2-( p-hydroxyanilino)-4-( p-chlorophenyl) thiazole], was nebulized for 30 min before OVA inhalation. OVA inhalation caused S1P release into BAL fluid and high expression of SPHK1 around bronchial epithelial walls and inflammatory areas. DMS or SK-I inhalation resulted in a decrease in S1P amounts in BAL fluid to basal levels, accompanied by decreased eosinophil infiltration and peroxidase activity. The extent of inhibition caused by DMS inhalation was higher than that caused by SK-I. Like T helper 2 (Th2) cytokine release, OVA inhalation-induced increase in eotaxin expression was significantly suppressed by DMS pretreatment both at protein level in BAL fluid and at mRNA level in lung homogenates. Moreover, bronchial hyperresponsiveness to inhaled methacholine and goblet cell hyperplasia were improved by SPHK inhibitors. These data suggest that the inhibition of SPHK affected acute eosinophilic inflammation induced in antigen-challenged mouse model and that targeting SPHK may provide a novel therapeutic tool to treat bronchial asthma.
Short-term exposure to cigarette smoke induces endothelial dysfunction in small intrapulmonary arteries: analysis using guinea pig precision cut lung slices
Authors: Wright J. L. , Churg A.
Published: March 2008

The pathogenesis of cigarette smoke-induced pulmonary hypertension is not understood. We have previously shown that smoke rapidly and persistently, but discoordinately, upregulates gene expression of mediators that control vasoconstriction, vasoproliferation, and vasorelaxation in small intrapulmonary arteries. To investigate the possibility that smoke also induces endothelial dysfunction, a finding common to other forms of pulmonary hypertension, we exposed guinea pigs to smoke or air (control) daily for 2 wk and then prepared precision-cut lung slices. After exposure to endothelin-1, a vasoconstrictor, intra-acinar arteries in lung slices derived from smoke-exposed animals constricted more rapidly (greater constriction at a given concentration of endothelin) than did vessels from air-exposed animals. To examine relaxation responses, arteries were constricted with the vasconstrictor U-46619 and then relaxed with progressively increasing doses of acetylcholine. Vessels from smokers had a delayed response to acetylcholine compared with vessels from controls. The NO synthase inhibitor NG-nitro-l-arginine methyl ester reduced relaxation in both control and smoke-exposed arteries, whereas the NO donor sodium nitroprusside increased relaxation of the smoke-exposed arteries, confirming that endothelial dysfunction with decreased effective NO production is present. These findings show that precision cut lung slices can be used to examine the physiological effects of cigarette smoke on intra-acinar pulmonary arteries and indicate that even relatively short-term exposure to smoke produces endothelial dysfunction with a resulting tendency to earlier constriction and later relaxation in cigarette smokers. These changes may be important in the development of pulmonary hypertension.
Modulation of the dystrophin-associated protein complex in response to resistance training in young and older men
Authors: Kosek David J. , Bamman Marcas M.
Published: March 2008

The dystrophin-associated protein complex (DAPC) is a scaffold of proteins linking the intracellular cytoskeleton with the extracellular matrix that is integral to structural stability and integrity, signaling and mechanotransduction, and force transmission. We hypothesized that the expression of DAPC component proteins would be altered by resistance loading during progressive resistance training (PRT)-mediated myofiber hypertrophy, and we investigated whether aging influenced these changes. Seventeen young (27 yr) and 13 older (65 yr) men completed 16 wk of PRT with muscle biopsies at baseline (T1), 24 h after bout 1 (T2), and 24 h after the final bout at week 16 (T3). Myofiber hypertrophy in the young (type I 31%, P < 0.005; type II 40%, P < 0.001) far exceeded hypertrophy in the old (type II only, 19.5%, P < 0.05). PRT altered protein expression for caveolin-3 (decreased 24% by T3, P < 0.01), α1-syntrophin (increased 16% by T3, P < 0.05), α-dystrobrevin (fell 23% from T2 to T3, P < 0.01), and dystrophin [rose acutely (30% by T2, P < 0.05) and returned to baseline by T3]. The phosphorylation state of membrane neuronal nitric oxide synthase (Ser1417) decreased 70% ( P < 0.005) by T3, particularly in the old (81%), whereas p38 MAPK phosphorylation increased twofold by T3 in the old ( P < 0.01). We conclude that component proteins of the DAPC are modulated by PRT, which may serve to improve both structural and signaling functions during load-mediated myofiber hypertrophy. The blunted hypertrophic adaptation seen in old vs. young men may have resulted from overstress, as suggested by marked p38 MAPK activation in old men only.
Hyperventilation evoked by activation of the vicinity of the caudal inferior olivary nucleus depends on the fastigial nucleus in anesthetized rats
Authors: Zhuang Jianguo , Xu Fadi , Frazier Donald T.
Published: March 2008

Several studies have demonstrated that cerebellar deep nuclei, particularly the rostral fastigial nucleus (FNr), are involved in respiratory modulation. These nuclei receive inputs from the contralateral caudal inferior olivary nuclei of the medulla. The objectives of this study were to determine whether electrical and chemical activation of the vicinity of the caudal inferior olivary nuclei (vIOc) affected respiration and, if true, whether the FNr was involved in the vIOc stimulation-evoked ventilatory responses. Experiments were conducted in 30 anesthetized and spontaneously breathing rats. Our results showed that 1) electrical (25 or 100 μA at 10 or 20 Hz for 10 s) and chemical (1 or 100 mM, 25–50 nl N-methyl-d-aspartate) stimulation of the vIOc augmented ventilation predominantly via increasing tidal volume; 2) the responses to the electrical stimulation were almost eliminated by lesion of the contralateral FNr via microinjection of ibotenic acid; and 3) the respiratory responses to electrical stimulation in the vicinity of the rostral IO were 65–70% smaller compared with that evoked by vIOc stimulation. These findings strongly suggest that vIOc neurons play a significant role in modulation of respiratory activity, largely depending on their projections to the FNr.
Electromyographic measures of muscle activation and changes in muscle architecture of human elbow flexors during fatiguing contractions
Authors: Rudroff Thorsten , Staudenmann Didier , Enoka Roger M.
Published: March 2008

The study compared changes in intramuscular and surface recordings of EMG amplitude with ultrasound measures of muscle architecture of the elbow flexors during a submaximal isometric contraction. Ten subjects performed a fatiguing contraction to task failure at 20% of maximal voluntary contraction force. EMG activity was recorded in biceps brachii, brachialis, and brachioradialis muscles using intramuscular and surface electrodes. The rates of increase in the amplitude of the surface EMG for the long and short heads of biceps brachii and brachioradialis were greater than those for the intramuscular recordings measured at different depths. The amplitude of the intramuscular recordings from three muscles increased at a similar rate ( P = 0.13), as did the amplitude of the three surface recordings from two muscles ( P = 0.83). The increases in brachialis thickness (27.7 ± 5.7 to 30.9 ± 3.5 mm; P < 0.05) and pennation angle (10.9 ± 3.5 to 16.5 ± 4.8°; P = 0.003) were not associated with the increase in intramuscular EMG amplitude ( P > 0.58). The increase in brachioradialis thickness (22.8 ± 4.8 to 25.5 ± 3.4 mm; P = 0.0075) was associated with the increase in the amplitude for one of two intramuscular EMG signals ( P = 0.007, r = 0.79). The time to failure was more strongly associated with the rate of increase in the amplitude of the surface EMG than that for the intramuscular EMG, which suggests that the surface measurement provides a more appropriate measure of the change in muscle activation during a fatiguing contraction.
Effect of heterogeneous ventilation and nitric oxide production on exhaled nitric oxide profiles
Authors: Suresh Vinod , Shelley David A. , Shin Hye-Won , George Steven C.
Published: March 2008

Elevated exhaled nitric oxide (NO) in the breath of asthmatic subjects is thought to be a noninvasive marker of lung inflammation. Asthma is also characterized by heterogeneous bronchoconstriction and inflammation, which impact the spatial distribution of ventilation in the lungs. Since exhaled NO arises from both airway and alveolar regions, and its level in exhaled breath depends strongly on flow, spatial heterogeneity in flow patterns and NO production may significantly affect the exhaled NO signal. To investigate the effect of these factors on exhaled NO profiles, we developed a multicompartment mathematical model of NO exchange using a trumpet-shaped central airway segment that bifurcates into two similarly shaped peripheral airway segments, each of which empties into an alveolar compartment. Heterogeneity in flow alone has only a minimal impact on the exhaled NO profile. In contrast, placing 70% of the total airway NO production in the central compartment or the distal poorly ventilated compartment can significantly increase (35%) or decrease (−10%) the plateau concentration, respectively. Reduced ventilation of the peripheral and acinar regions of the lungs with concomitant elevated NO production delays the rise of NO during exhalation, resulting in a positive phase III slope and reduced plateau concentration (−11%). These features compare favorably with experimentally observed profiles in exercise-induced asthma and cannot be simulated with single-path models. We conclude that variability in ventilation and NO production in asthmatic subjects impacts the shape of the exhaled NO profile and thus impacts the physiological interpretation.
Kinetics of muscle deoxygenation are accelerated at the onset of heavy-intensity exercise in patients with COPD: relationship to central cardiovascular dynamics
Authors: Chiappa Gaspar R. , Borghi-Silva Audrey , Ferreira Leonardo F. , Carrascosa Claúdia , Oliveira Cristino Carneiro , Maia Joyce , Gimenes Ana Cristina , Queiroga Fernando , Berton Danilo , Ferreira Eloara M. V. , Nery Luis Eduardo , Neder J. Alberto
Published: March 2008

Patients with chronic obstructive pulmonary disease (COPD) have slowed pulmonary O2uptake (V̇o2p) kinetics during exercise, which may stem from inadequate muscle O2delivery. However, it is currently unknown how COPD impacts the dynamic relationship between systemic and microvascular O2delivery to uptake during exercise. We tested the hypothesis that, along with slowed V̇o2pkinetics, COPD patients have faster dynamics of muscle deoxygenation, but slower kinetics of cardiac output (Q̇t) following the onset of heavy-intensity exercise. We measured V̇o2p, Q̇t (impedance cardiography), and muscle deoxygenation (near-infrared spectroscopy) during heavy-intensity exercise performed to the limit of tolerance by 10 patients with moderate-to-severe COPD and 11 age-matched sedentary controls. Variables were analyzed by standard nonlinear regression equations. Time to exercise intolerance was significantly ( P < 0.05) lower in patients and related to the kinetics of V̇o2p( r = −0.70; P < 0.05). Compared with controls, COPD patients displayed slower kinetics of V̇o2p(42 ± 13 vs. 73 ± 24 s) and Q̇t (67 ± 11 vs. 96 ± 32 s), and faster overall kinetics of muscle deoxy-Hb (19.9 ± 2.4 vs. 16.5 ± 3.4 s). Consequently, the time constant ratio of O2uptake to mean response time of deoxy-Hb concentration was significantly greater in patients, suggesting a slower kinetics of microvascular O2delivery. In conclusion, our data show that patients with moderate-to-severe COPD have impaired central and peripheral cardiovascular adjustments following the onset of heavy-intensity exercise. These cardiocirculatory disturbances negatively impact the dynamic matching of O2delivery and utilization and may contribute to the slower V̇o2pkinetics compared with age-matched controls.
Abdominal Obesity and the Metabolic Syndrome: Contribution to Global Cardiometabolic Risk
Authors: Després Jean-Pierre , Lemieux Isabelle , Bergeron Jean , Pibarot Philippe , Mathieu Patrick , Larose Eric , Rodés-Cabau Josep , Bertrand Olivier F. , Poirier Paul
Published: March 2008

There is currently substantial confusion between the conceptual definition of the metabolic syndrome and the clinical screening parameters and cut-off values proposed by various organizations (NCEP-ATP III, IDF, WHO, etc) to identify individuals with the metabolic syndrome. Although it is clear that in vivo insulin resistance is a key abnormality associated with an atherogenic, prothrombotic, and inflammatory profile which has been named by some the “metabolic syndrome” or by others “syndrome X” or “insulin resistance syndrome”, it is more and more recognized that the most prevalent form of this constellation of metabolic abnormalities linked to insulin resistance is found in patients with abdominal obesity, especially with an excess of intra-abdominal or visceral adipose tissue. We have previously proposed that visceral obesity may represent a clinical intermediate phenotype reflecting the relative inability of subcutaneous adipose tissue to act as a protective metabolic sink for the clearance and storage of the extra energy derived from dietary triglycerides, leading to ectopic fat deposition in visceral adipose depots, skeletal muscle, liver, heart, etc. Thus, visceral obesity may partly be a marker of a dysmetabolic state and partly a cause of the metabolic syndrome. Although waist circumference is a better marker of abdominal fat accumulation than the body mass index, an elevated waistline alone is not sufficient to diagnose visceral obesity and we have proposed that an elevated fasting triglyceride concentration could represent, when waist circumference is increased, a simple clinical marker of excess visceral/ectopic fat. Finally, a clinical diagnosis of visceral obesity, insulin resistance, or of the metabolic syndrome is not sufficient to assess global risk of cardiovascular disease. To achieve this goal, physicians should first pay attention to the classical risk factors while also considering the additional risk resulting from the presence of abdominal obesity and the metabolic syndrome, such global risk being defined as cardiometabolic risk.
Homocysteine or Renal Impairment
Authors: Potter Kathleen , Hankey Graeme J. , Green Daniel J. , Eikelboom John W. , Arnolda Leonard F.
Published: March 2008

Objective—

The purpose of this study was to determine whether adjustment for renal function eliminates the relationship between total plasma homocysteine (tHcy) and vascular risk, assessed by carotid intima medial thickness (CIMT) and flow-mediated dilation (FMD) of the brachial artery.

Methods and Results—

We used cross-sectional data from 173 stroke patients treated with B-vitamins (folic acid 2 mg, vitamin B
6
25 mg, and vitamin B
12
0.5 mg) or placebo in a randomized double-blinded trial to test the relationships between posttreatment tHcy, cystatin C (a marker of glomerular filtration rate), estimated glomerular filtration rate (eGFR, Modification of Diet in Renal Disease equation) creatinine, CIMT, and FMD in stepwise and multivariable regression models. The strong linear relationship between tHcy and cystatin C was not altered by long-term B-vitamin treatment. tHcy lost significance as a predictor of the vascular measurements after adjustment for any single marker of renal function. Cystatin C, but not tHcy, was a significant independent predictor of FMD after adjustment for age, sex, smoking, systolic blood pressure, high-density lipoprotein cholesterol, and treatment group.

Conclusions—

Adjusting for renal function eliminates the relationship between tHcy and CIMT and FMD, supporting the hypothesis that elevated tHcy is a marker for renal impairment rather than an independent cardiovascular risk factor.
Sympathetic Activation Causes Focal Adhesion Signaling Alteration in Early Compensated Volume Overload Attributable to Isolated Mitral Regurgitation in the Dog
Authors: Sabri Abdelkarim , Rafiq Khadija , Seqqat Rachid , Kolpakov Mikhail A. , Dillon Ray , Dell’italia Louis J.
Published: March 2008

We reported that left ventricular (LV) dilatation after 4 weeks of isolated mitral regurgitation (MR) in the dogs is marked by extracellular matrix loss and an increase in adrenergic drive. Given that extracellular matrix proteins and their receptor integrins influence β-adrenergic receptor (β-AR) responses in vitro, we tested whether β1-AR activation modulates focal adhesion (FA) signaling and LV remodeling in these same dogs with isolated MR. Normal dogs were compared with dogs with MR of a 4-week duration and with MR dogs treated with β
1
-AR blockade (β
1
-RB) (extended-release metoprolol succinate, 100 mg QD) that was started 24 hours after MR induction. In MR LVs, a decrease in collagen accumulation compared with normal dogs was associated with a decrease in FA kinase tyrosine phosphorylation, along with FA kinase interaction with adapter and cytoskeletal proteins, p130
Cas
and paxillin, respectively, as determined by immunoprecipitation assays. There was increased phosphorylation of stress related molecules p38 mitogen-activated protein kinase (MAPK) and Hsp27 and survival signaling kinases extracellular signal-regulated kinase 1/2 and AKT, with no evidence of cardiomyocyte apoptosis. β
1
-RB attenuated FA signaling loss and prevented p38 MAPK, Hsp27, and AKT phosphorylation induced by MR and significantly increased LV epicardial collagen content. However, β
1
-RB did not improve LV endocardial collagen loss or LV dilatation induced by MR. Isolated myocytes from normal and MR dog hearts treated with β
1
- or β
2
-AR agonists demonstrated no difference in FA kinase, p38 MAPK, Hsp27, or AKT phosphorylation. These results showed that chronic stimulation of β
1
-AR during early compensated MR impairs FA signaling that may affect myocyte/fibroblast–extracellular matrix scaffolding necessary for LV remodeling.
Circulating Endothelial Progenitor Cells as a New Marker of Endothelial Dysfunction or Repair in Acute Stroke
Authors: Chu Kon , Jung Keun-Hwa , Lee Soon-Tae , Park Hee-Kwon , Sinn Dong-In , Kim Jeong-Min , Kim Dong-Hyun , Kim Jin-Hee , Kim Se-Jeong , Song Eun-Cheol , Kim Manho , Lee Sang Kun , Roh Jae-Kyu
Published: March 2008

Background and Purpose—

Understanding on distinct subsets of endothelial progenitor cells may provide insights of endothelial dysfunction or repair in the acute ischemic event. Recent in vitro data have reported the colony-forming unit (CFU) and outgrowth cell population as a subset of endothelial progenitor cells. In this study, we undertook to validate the significance of CFU number and outgrowth cell yield in acute stroke.

Methods—

Mononuclear cells were isolated from the peripheral blood of 75 patients with acute stroke, 45 patients with chronic stroke, and 40 age-matched healthy volunteers. CFU numbers were counted after culturing them for 7 days, and outgrowth cell appearance was measured during the 2 months of culture. Endothelial progenitor cell function was also evaluated by matrigel plate assays. Independent parameters predicting CFU number and outgrowth cell yield were assessed using logistic regression analysis.

Results—

The CFU numbers and tube formation abilities in matrigel assays were significantly reduced in patients with acute stroke compared with patients with chronic stroke or healthy control subjects. Moreover, patients with large artery atherosclerosis had much lower CFU numbers and functional activities than ones with cardioembolism. Outgrowth cells were isolated from 10% of healthy control subjects and 22% of patients with chronic stroke during the cultures, but from 71% of patients with stroke. Multivariate analysis identified glycosylated hemoglobin and National Institutes of Health Stroke Scale on admission as significant independent predictors of a low CFU number and a high isolation frequency of outgrowth cells, respectively.

Conclusion—

CFU number may thus represent an accumulated endothelial progenitor cell dysfunctional status, whereas outgrowth cell appearance may reflect the resilience of the systemic circulation to acute ischemic stress.
Quantification of Microspheres Appearance in Brain Vessels
Authors: Sharma Vijay K. , Tsivgoulis Georgios , Lao Annabelle Y. , Malkoff Marc D. , Alexandrov Anne W. , Alexandrov Andrei V.
Published: March 2008

Background and Purpose—

Characteristics of ultrasound-activated gaseous microspheres (μS) reflective of their size and quantities are needed for future dose-escalation and drug delivery trials.

Methods—

A double-blind, interobserver-validated analysis of multi-gate power-motion Doppler μS traces included large (>8μ) μS from agitated saline injections in the right-to-left shunt (RLS) positive stroke patients and small (<5μ) μS from acute patients without shunts receiving thrombolysis and perflutren-lipid μS.

Results—

In 101 μS traces from 50 RLS-positive and 10 thrombolysis+μS treated patients, a large μS passage had median maximum duration 30.8 ms (interquartile range [IQR] 22.0ms), multi-gate travel time (MGTT) 58.6±19.3 ms versus small μS: duration 8.3ms (IQR 4.3ms), MGTT 43.2±13.9ms,
P
<0.001. Small μS had higher embolus-to-blood ratio (EBR): 17.5 (IQR 9.3) versus 7.5 (IQR 4),
P
<0.001. Receiver-operating curve areas were: duration 0.989 (95% CI 0.968 to 1.000), MGTT 0.766 (0.672 to 0.859), and EBR (Embolus-to-Blood Ratio) 0.927 (0.871 to 0.982),
P
<0.001. A 15.1-ms duration discriminated size ranges with 98% to 99% accuracy. On average, 130 sequential large (range 51 to 260) and 500 (265–588) small μS can produce continuous flow enhancement for 4 seconds. Small μS velocities on m-mode in obstructed vessels (39.8±11.3 cm/s) were similar to large μS in patent vessels (40.8±11.5 cm/s;
P
=0.719) and higher than surrounding red blood cell velocities (28.8±13.8 cm/s,
P
<0.001).

Conclusions—

With normal or reduced flow, activated μS passage duration through a small power motion Doppler gate can quantify the dose of delivered μS. Ultrasound can determine a minimum number of μS needed to achieve constant flow enhancement and targeted drug delivery. Propagation speed of μS smaller than red blood cells may reflect plasma flow velocities around acute occlusions.
Angiogenesis Detected After Embolic Stroke in Rat Brain Using Magnetic Resonance T2*WI
Authors: Ding Guangliang , Jiang Quan , Li Lian , Zhang Li , Zhang Zheng Gang , Ledbetter Karyn A. , Gollapalli Lakshman , Panda Swayamprava , Li Qingjiang , Ewing James R. , Chopp Michael
Published: March 2008

Background and Purpose—

This study uses T
2
* weighted imaging (T2*WI) to measure the temporal evolution of cerebral angiogenesis in rats subjected to embolic stroke up to 6 weeks after stroke onset with or without sildenafil treatment.

Method—

Male Wistar rats were subjected to embolic stroke and treated with saline (n=10) or with sildenafil (n=11), with treatment initiated at 24 hours and continued daily for 7 days after onset of ischemia. T2*WI measurements were performed at 24 hours after embolization and weekly up to 6 weeks using a 7-Tesla system. Histological measurements were obtained at 6 weeks after MRI scans.

Results—

Using T2*WI, cerebral angiogenesis was detected starting from 4 weeks and from 2 weeks after onset of embolic stroke in saline and sildenafil treated rats, respectively. Significant differences in the temporal and spatial features of angiogenesis after embolic stroke up to 6 weeks after onset of stroke were found between saline and sildenafil treated rats and were identified with T2*WI. MRI permeability parameter, K
i
, complementarily detected angiogenesis after ischemia in embolic stroke rats. Sildenafil treatment of stroke rats significantly enhanced the angiogenesis, as confirmed histologically.

Conclusions—

T2*WI can quantitatively measure the temporal evolution of angiogenesis in rats subjected to embolic stroke. Compared to control rats, sildenafil treatment significantly increased angiogenesis in treated animals up to 6 weeks after stroke.
Enhanced Expression of Lp-PLA
2
and Lysophosphatidylcholine in Symptomatic Carotid Atherosclerotic Plaques
Authors: Mannheim Dallit , Herrmann Joerg , Versari Daniele , Gössl Mario , Meyer Fredric B. , McConnell Joseph P. , Lerman Lilach O. , Lerman Amir
Published: March 2008

Background and Purpose—

Circulating lipoprotein-associated phospholipase A
2
(Lp-PLA
2
) has emerged as a novel biomarker for cardiovascular diseases. However, the correlation between the plaque expression of Lp-PLA
2
and plaque oxidative stress, inflammation, and stability as well as the clinical presentation remains poorly defined, especially for cerebrovascular disease. Therefore, this study was performed to test the hypothesis that Lp-PLA
2
expression is higher in symptomatic than in asymptomatic carotid plaques of patients undergoing carotid endarterectomy.

Methods—

The expression of Lp-PLA
2
in 167 carotid artery plaques was determined by immunoblotting and immunostaining. Plaque oxidative stress, inflammation, and stability were quantified by NAD(P)H oxidase p67phox and MMP-2 immunoblotting, oxidized LDL (oxLDL) immunoreactivity, macrophage and Sirius red collagen staining. Lysophosphatidylcholine 16:0 (lysoPC) concentration was measured in 55 plaques using liquid chromatography tandem mass spectrometry.

Results—

Lp-PLA
2
expression was significantly higher in plaques of symptomatic patients than asymptomatic patients (1.66±0.19 versus 1.14±0.10,
P
<0.05) and localized mainly to shoulder and necrotic lipid core areas in colocalization with oxLDL and macrophage content. Similarly, Lp-PLA
2
expression was related to collagen content, which was lower in plaques from symptomatic patients than in plaques from asymptomatic patients (9.1±2.2 versus 18.5±1.7% of staining/field,
P
<0.001). LysoPC plaque concentration was significantly higher in plaques of symptomatic than asymptomatic patients (437.0±57.91 versus 228.84±37.00 mmol/L,
P
<0.05).

Conclusions—

Symptomatic carotid artery plaques are characterized by increased levels of Lp-PLA
2
and its product lysoPC in correlation with markers of tissue oxidative stress, inflammation, and instability. These findings strongly support a role for Lp-PLA2 in the pathophysiology and clinical presentation of cerebrovascular disease.
Use of a Local Worker Survey as a Source of Neighborhood Information
Authors: Strycker Lisa A. , Duncan Susan C. , Duncan Terry E. , Chaumeton Nigel R. , He Haiou
Published: March 2008

Researchers increasingly recognize the potential influence of the neighborhood environment on individual health and social behavior. To examine these influences, it is important to use varying measures and sources of neighborhood characteristics. Though neighborhood residents are often surveyed, the perceptions of neighborhood workers have been largely ignored. The current study documents procedures and findings from two longitudinal studies in which workers in 60 neighborhoods were surveyed about neighborhood social cohesion and social control (collective efficacy), and neighborhood problems. Results indicated that workers within neighborhoods were more homogeneous in their views of neighborhood collective efficacy and neighborhood problems than were workers across neighborhoods. In addition, not only were workers' perceptions of their neighborhoods similar to the perceptions of neighborhood residents but they also provided unique information. Overall, this study demonstrates the viability and usefulness of local workers as an additional source of neighborhood information.
Predictors of Two Types of Earthquake Preparation
Authors: Spittal Matthew J. , McClure John , Siegert Richard J. , Walkey Frank H.
Published: March 2008

There is a need to clarify why people who are at risk from natural disasters such as earthquakes are often less prepared than they could be. This study of residents in Wellington, New Zealand ( N = 358), tested demographic and psychological predictors of two aspects of earthquake preparation: survival actions (e.g., storing water) and damage-mitigation actions (e.g., fastening bookshelves or securing foundations). Psychological predictors were participants' tendency to take risks and their locus of control; significant demographic predictors were home ownership and length of residence. When demographic factors were taken into account, risk-taking tendency predicted earthquake preparation in general and survival actions in particular, but not mitigation actions. In contrast, locus of control predicted mitigation actions. These findings extend existing theories and show the value of measuring mitigation actions as well as survival actions.
Reintroducing Adventure Into Children's Outdoor Play Environments
Authors: Staempfli Marianne B.
Published: March 2008

Over the last decade, awareness about the changing nature of children's play has gradually increased, leading to some concerns that outdoor play, particularly unstructured outdoor play, is rapidly declining. Reasons for these changes are diverse and multilayered, rooted in ever-evolving sets of social and parental expectations and the children's needs for entertainment and self-expression. Parents are struggling with competing, rational, and emotive judgments (personal and social in nature) about positive and negative risks associated with play. As suggested in this article, adventure playgrounds are a specific type of outdoor play environments that have the potential to offer an abundance of developmental opportunities for children to grow emotionally, socially, and physically.
Edward W. Blyden, “The Jewish Question,” and the Diaspora
Authors: Echeruo Michael J. C.
Published: March 2008

Dr. Blyden’s booklet, “The Jewish Question,” has been largely ignored, as it relates not only to the Jewish Question, proper, but also to the question of African American identifications with Africa and the quest to return, in one sense or another, to the “land of their fathers.” This article examines all of these three aspects of Blyden’s work and suggests in what ways the idea of a Diaspora could be understood in theory and in practice, considering Blyden’s attitudes.
Health Technology Assessment in the Cost-Disutility Plane
Authors: Eckermann Simon , Briggs Andrew , Willan Andrew R.
Published: March 2008

Previously, comparisons of multiple strategies in health technology assessment have been undertaken on the incremental cost-effectiveness plane using efficiency frontiers and cost-effectiveness acceptability curves. This article proposes shifting the comparison of multiple strategies to the cost-disutility plane. Evidence-based decision making requires comparison of all strategies against each other. Consequently, the origin in the incremental cost-effectiveness plane cannot be the appropriate reference point in comparing multiple nondominated strategies. A linear transformation onto the cost-disutility plane allows an equivalent comparison of net benefit and permits the use of standard efficiency measurement methods to estimate 1) the degree of dominance (technical inefficiency) of dominated strategies and 2) the net benefit inefficiency (i.e., losses in net benefit relative to an optimal strategy). In comparing strategies under uncertainty, a comparison of loss in net benefit leads to the expected net loss frontier, which, unlike cost effectiveness acceptability curves, directly identifies differences in expected net benefit (net loss) and the expected value of perfect information. Thus, decision makers can be better informed about the choice of optimal strategy and the potential value of future research to resolve uncertainty. Comparing strategies in the cost-disutility plane is suggested to better inform decision making and to provide a link between the cost-effectiveness literature and efficiency measurement methods.
A Spiritually Based Group Intervention for Combat Veterans With Posttraumatic Stress Disorder
Authors: Bormann Jill E. , Thorp Steven , Wetherell Julie L. , Golshan Shahrokh
Published: March 2008

Purpose: To assess the feasibility, effect sizes, and satisfaction of mantram repetition—the spiritual practice of repeating a sacred word/phrase throughout the day—for managing symptoms of posttraumatic stress disorder (PTSD) in veterans. Design: A two group (intervention vs. control) by two time (pre- and postintervention) experimental design was used. Methods: Veterans were randomly assigned to intervention ( n = 14) or delayed-treatment control ( n = 15). Measures were PTSD symptoms, psychological distress, quality of life, and patient satisfaction. Effect sizes were calculated using Cohen's d. Findings: Thirty-three male veterans were enrolled, and 29 (88%) completed the study. Large effect sizes were found for reducing PTSD symptom severity ( d = –.72), psychological distress ( d = –.73) and increasing quality of life ( d = –.70). Conclusions: A spiritual program was found to be feasible for veterans with PTSD. They reported moderate to high satisfaction. Effect sizes show promise for symptom improvement but more research is needed.
Changing the Way Employees Interact With Guests With Disabilities
Authors: Hall Elizabeth W.
Published: March 2008

The purpose of this study was to investigate the effectiveness of a disability awareness workshop and its effect on theme park employees. Two research questions were posed: Would employees who attended a disability awareness workshop demonstrate a greater knowledge base in disability issues and legislation? Would they alter their attitudes toward persons with disabilities? The 40 employees participating in this study were given the Facts About Disabilities Scale (FAD) and the Interaction With Disabled Persons Scale (IDP) as a pretest. Employees in the treatment group attended a 1-day disability awareness workshop. Following the workshop, all employees were given the FAD and the IDP as a posttest. A repeated-measures analysis of covariance revealed statistically significant differences in the knowledge levels of employees and more positive attitudes toward guests with disabilities as a result of attending the disability awareness workshop. Conclusions and recommendations for further research are provided.