bluuebunny/crossref_metadata_2025 huggingface dataset:
High-altitude exposure of three weeks duration increases lung diffusing capacity in humans
Authors: Agostoni Piergiuseppe , Swenson Erik R. , Bussotti Maurizio , Revera Miriam , Meriggi Paolo , Faini Andrea , Lombardi Carolina , Bilo Grzegorz , Giuliano Andrea , Bonacina Daniele , Modesti Pietro A. , Mancia Giuseppe , Parati Gianfranco
Published: March 2011

Background: high-altitude adaptation leads to progressive increase in arterial PaO2. In addition to increased ventilation, better arterial oxygenation may reflect improvements in lung gas exchange. Previous investigations reveal alterations at the alveolar-capillary barrier indicative of decreased resistance to gas exchange with prolonged hypoxia adaptation, but how quickly this occurs is unknown. Carbon monoxide lung diffusing capacity and its major determinants, hemoglobin, alveolar volume, pulmonary capillary blood volume, and alveolar-capillary membrane diffusion, have never been examined with early high-altitude adaptation. Methods and Results: lung diffusion was measured in 33 healthy lowlanders at sea level (Milan, Italy) and at Mount Everest South Base Camp (5,400 m) after a 9-day trek and 2-wk residence at 5,400 m. Measurements were adjusted for hemoglobin and inspired oxygen. Subjects with mountain sickness were excluded. After 2 wk at 5,400 m, hemoglobin oxygen saturation increased from 77.2 ± 6.0 to 85.3 ± 3.6%. Compared with sea level, there were increases in hemoglobin, lung diffusing capacity, membrane diffusion, and alveolar volume from 14.2 ± 1.2 to 17.2 ± 1.8 g/dl ( P < 0.01), from 23.6 ± 4.4 to 25.1 ± 5.3 ml·min−1·mmHg−1( P < 0.0303), 63 ± 34 to 102 ± 65 ml·min−1·mmHg−1( P < 0.01), and 5.6 ± 1.0 to 6.3 ± 1.1 liters ( P < 0.01), respectively. Pulmonary capillary blood volume was unchanged. Membrane diffusion normalized for alveolar volume was 10.9 ± 5.2 at sea level rising to 16.0 ± 9.2 ml·min−1·mmHg−1·l−1( P < 0.01) at 5,400 m. Conclusions: at high altitude, lung diffusing capacity improves with acclimatization due to increases of hemoglobin, alveolar volume, and membrane diffusion. Reduction in alveolar-capillary barrier resistance is possibly mediated by an increase of sympathetic tone and can develop in 3 wk.
Cardiac function following prolonged exercise: influence of age
Authors: Banks Laura , Sasson Zion , Esfandiari Sam , Busato Gian-Marco , Goodman Jack M.
Published: March 2011

This study sought to determine the influence of age on the left ventricular (LV) response to prolonged exercise (PE; 150 min). LV systolic and diastolic performance was assessed using echocardiography (ECHO) before (pre) and 60 min following (post) exercise performed at 80% maximal aerobic power in young (28 ± 4.5 years; n = 18; mean ± SD) and middle-aged (52 ± 3.9 years; n = 18) participants. LV performance was assessed using two-dimensional ECHO, including speckle-tracking imaging, to determine LV strain (LV S) and LV S rate (LV SR), in addition to Doppler measures of diastolic function. We observed a postexercise elevation in LV S (young: −19.5 ± 2.1% vs. −21.6 ± 2.1%; middle-aged: −19.9 ± 2.3% vs. −20.8 ± 2.1%; P < 0.05) and LV SR (young: −1.19 ± 0.1 vs. −1.37 ± 0.2; middle-aged: −1.20 ± 0.2 vs. −1.38 ± 0.2; P < 0.05) during recovery in both groups. Diastolic function was reduced during recovery, including the LV SR ratio of early-to-late atrial diastolic filling (SRe/a), in young (2.35 ± 0.7 vs. 1.89 ± 0.5; P < 0.01) and middle-aged (1.51 ± 0.5 vs. 1.05 ± 0.2; P < 0.01) participants, as were conventional indices including the E/A ratio. Dobutamine stress ECHO revealed a postexercise depression in LV S in response to increasing dobutamine dose, which was similar in both young (pre-exercise dobutamine 0 vs. 20 μg·kg−1·min−1: −19.5 ± 2.1 vs. −27.2 ± 2.2%; postexercise dobutamine 0 vs. 20 μg·kg−1·min−1: −21.6 ± 2.1 vs. −23.7 ± 2.2%; P < 0.05) and middle-aged participants (pre: −19.9 ± 2.3 vs. −25.3 ± 2.7%; post: −20.8 ± 2.1 vs. −23.5 ± 2.7; P < 0.05). This was despite higher noradrenaline concentrations immediately postexercise in the middle-aged participants compared with young (4.26 ± 2.7 nmol/L vs. 3.00 ± 1.4 nmol/L; P = 0.12). These data indicate that LV dysfunction is observed following PE and that advancing age does not increase the magnitude of this response.
Helicobacter pyloriPrevalence and Circulating Micronutrient Levels in a Low-Income United States Population
Authors: Epplein Meira , Signorello Lisa B. , Zheng Wei , Cai Qiuyin , Hargreaves Margaret K. , Michel Angelika , Pawlita Michael , Fowke Jay H. , Correa Pelayo , Blot William J.
Published: March 2011

High prevalence of Helicobacter pylori (H. pylori), the leading cause of gastric cancer, and low levels of micronutrients have been observed in many developing countries, and the question remains as to the whether an association between the 2 exists. The present study seeks to further our understanding of this potential connection in the Southern Community Cohort Study, representing a low-income population in the United States. Blood levels of antibodies to H. pylori proteins were assessed by multiplex serology for a sample of 310 African American and white participants, ages 40 to 79 years. Blood collected at baseline was also assayed for levels of carotenoids, tocopherols, retinol, and folate. Multivariate linear regression was used to calculate least-squares mean micronutrient levels within groups defined by H. pylori status. The mean serum levels of all micronutrients assayed were lower among H. pylori + individuals than H. pylori − individuals, significantly for β-carotene, folate, and retinol (decreases of 27.6%, 18.6%, and 9.7%, respectively). Individuals who were seropositive to the virulent CagA+ H. pylori strains had even lower mean levels of micronutrients, particularly β-carotene, folate, total carotenoids, and retinol (decreases of 38.9%, 19.1%, 17.0%, and 11.7%, respectively, compared with H. pylori − individuals). However, dietary micronutrient levels as derived from a food frequency questionnaire did not vary between groups defined by H. pylori status. These results provide support for the hypothesis that H. pylori infection impairs nutrient absorption and suggest a need for future studies to explore the role of H. pylori infection on nutrition and gastric cancer risk in this high-risk population. Cancer Prev Res; 4(6); 871–8. ©2011 AACR.
Reintroduction of Oxaliplatin: A Viable Approach to the Long-Term Management of Metastatic Colorectal Cancer
Authors: Grothey Axel
Published: March 2011

Oxaliplatin-based chemotherapy is an effective first-line treatment option for patients with metastatic colorectal cancer (mCRC), which, in combination with targeted therapies and a sequential treatment approach using all active agents, has extended median overall survival to 2 years and beyond. Prolonged survival brings into focus the burden of treatment, in terms of associated toxicities and quality of life, and attention is now being paid to lowering the toxicity burden for patients receiving chemotherapy for mCRC without compromising efficacy. The use of oxaliplatin can lead to the development of sensory neuropathy, which commonly limits the dose and/or duration of treatment that can be administered. Temporary withdrawal of oxaliplatin (treatment holidays) has been shown to be an effective strategy for the management of this adverse effect. Data from randomized controlled trials indicate that a formalized stop-and-go approach to the delivery of oxaliplatin does not compromise efficacy, and indeed for some patients may prove beneficial by allowing them to continue treatment for longer periods. This paper presents a critical review of the evidence to support the utility of treatment interruption and reintroduction of oxaliplatin for the long-term management of mCRC.
Eficacia y seguridad de la administración de hierro en poblaciones juveniles
Authors: Schümann Klaus , Solomons Noel W.
Published: March 2011

La anemia por carencia de hierro (ACH) del lactante reduce su capacidad cognitiva máxima de por vida y puede poner en riesgo la vida de una madre adolescente en el parto. La administración de hierro es un componente de las estrategias encaminadas a prevenir o invertir la carencia de hierro (CH), y el hierro puede administrarse por vía parenteral o mediante aportes complementarios o alimentos enriquecidos por vía oral. Pueden suscitarse problemas de seguridad en el lugar de administración, es decir, en la luz intestinal, que aparecerían a partir de las intervenciones como consecuencia de depósitos de hierro excesivos. Las mejoras recientes en la farmacología de los compuestos de hierro parenterales despejan el camino en terapia pediátrica e incluso en salud pública. El aporte complementario de hierro por vía oral, habitualmente junto al ácido fólico, es el tratamiento principal de la ACH en el entorno clínico. A menudo se combina con múltiples micronutrientes y se utiliza también para la resolución de la anemia grave en el ámbito extrahospitalario y para la profilaxis en la población no anémica. El enriquecimiento de alimentos básicos (como harina) o alimentos (leche para lactantes, alimentos complementarios) y bebidas específicos de la edad son los métodos habituales para la profilaxis de la CH. Se dispone de preparados especiales ricos en hierro (polvos, comprimidos disgregables, productos comestibles para untar) destinados al enriquecimiento casero. El bioenriquecimiento, es decir, el enriquecimiento del contenido en hierro de cosechas durante el cultivo es un abordaje novedoso que todavía tiene que ser puesto en práctica o evaluado íntegramente en relación con niños. En la luz intestinal se observan efectos secundarios y signos tóxicos tras la ingestión oral de hierro. Después de la administración oral y parenteral, el aumento del hierro circulatorio puede incrementar el riesgo de complicaciones a partir de infecciones coexistentes, especialmente en el caso del paludismo, y cuando el estado individual de hierro es suficiente. Se produce un deterioro del crecimiento en caso de exposición de niños con suficiencia de hierro a intervenciones con este nutriente, de manera que parece aconsejable orientar el hierro a individuos afectados de CH. Aparecen numerosas consecuencias adversas por la acumulación de depósitos de hierro excesivos en todo el cuerpo como resultado de la agresión oxidativa mediada por hierro. La maduración incompleta de la homeostasis del hierro puede permitir una mayor absorción de hierro antes de los 6 meses de edad.
Trajectories of Cognitive Decline following Dementia Onset: What Accounts for Variation in Progression?
Authors: MacDonald Stuart W.S. , Karlsson Sari , Fratiglioni Laura , Bäckman Lars
Published: March 2011

Background: Delineating the natural history of dementia progression has important clinical implications, including reducing caregiver burden and targeting effective drug trials. We examined whether trajectories of cognitive change differed reliably after diagnosis, and whether diverse predictors of such differences (demographic, psychological, biological, genetic, social) could be identified. Methods: Cognitive change was examined for incident dementia cases (mild: n = 156; moderate: n = 77; severe: n = 73) and controls (n = 249) from the Kungsholmen Project, a community-based study of adults 75 years and older. Results: For those with dementia, total variance attributed to between-person differences in cognitive decline was modest and linked to but a single predictor (history of cardiovascular disease). Although less variance in cognitive decline was observed for the similarly aged controls, numerous significant predictors of these differences were identified. Conclusion: The neurodegenerative process underlying dementia overshadows formerly significant predictors of cognitive change.
Imaging inflammatory plasma leakage in vivo
Authors: Lindbom Lennart , Kenne Ellinor
Published: March 2011

Increased vascular permeability and consequent plasma leakage from postcapillary venules is a cardinal sign of inflammation. Although the movement of plasma constituents from the vasculature to the affected tissue aids in clearing the inflammatory stimulus, excessive plasma extravasation can lead to hospitalisation or death in cases such as influenza-induced pneumonia, burns or brain injury. The use of intravital imaging has significantly contributed to the understanding of the mechanisms controlling the vascular permeability alterations that occur during inflammation. Today, intravital imaging can be performed using optical and non-optical techniques. Optical techniques, which are generally used in experimental settings, include traditional intravital fluorescence microscopy and near-infrared fluorescence imaging. Magnetic resonance (MRI) and radioisotopic imaging are used mainly in the clinical setting, but are increasingly used in experimental work, and can detect plasma leakage without optics. Although these methods are all able to visualise inflammatory plasma leakage in vivo, the spatial and temporal resolution differs between the techniques. In addition, they vary with regards to invasiveness and availability. This overview discusses the use of imaging techniques in the visualisation of inflammatory plasma leakage.
Allelic imbalance of tissue-type plasminogen activator (t-PA) gene expression in human brain tissue
Authors: Tjärnlund-Wolf Anna , Hultman Karin , Curtis Maurice , Faull Richard , Medcalf Robert , Jern Christina
Published: March 2011

We have identified a single-nucleotide polymorphism (SNP) in the t-PA enhancer (-7351C>T), which is associated with endothelial t-PA release in vivo. In vitro studies demonstrated that this SNP is functional at the level of transcription. In the brain, t-PA has been implicated in both physiologic and pathophysiologic processes. The aim of the present study was to examine the effect of the t-PA –7351C>T SNP on t-PA gene expression in human brain tissue. Allelic mRNA expression was measured in heterozygous post-mortem brain tissues using quantitative TaqMan genotyping assay. Protein-DNA interactions were assessed using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). Significantly higher levels of t-PA mRNA were generated from chromosomes that harboured the wild-type –7351C allele, as compared to those generated from the mutant T allele (for the hippocampus, C to T allelic ratio of ~1.3, p=0.010, n=12; and for the cortex, C to T allelic ratio of ~1.2, p=0.017, n=12). EMSA showed reduced neuronal and astrocytic nuclear protein binding affinity to the T allele, and identified Sp1 and Sp3 as the major transcription factors that bound to the –7351 site. ChIP analyses confirmed that Sp1 recognises this site in intact cells. In conclusion, the t-PA –7351C>T SNP affects t-PA gene expression in human brain tissue. This finding might have clinical implications for neurological conditions associated with enhanced t-PA levels, such as in the acute phase of cerebral ischaemia, and also for stroke recovery.
Erythrocyte membrane sulfatide plays a crucial role in the adhesion of sickle erythrocytes to endothelium
Authors: Zhou Zhou , Thiagarajan Perumal , Udden Mark , López José , Guchhait Prasenjit
Published: March 2011

Enhanced adhesion of sickle erythrocytes to the vascular endothelium and subendothelial matrix is fundamental to the development of vascular occlusion in sickle cell disease. Erythrocyte membrane sulfatide is implicated in the pathogenesis of vasoocclusive crises in sickle cell disease (SCD) patients. Because previous evidence linking sulfatide to cell adhesion has largely been circumstantial due to a lack of reagents that specifically target sulfatide, we used two sulfatide-specific strategies to address the role of erythrocyte membrane sulfatide in sickle cell adhesion to the vascular endothelium: a single-chain fragment variable chain (scFv) antibody against sulfatide as well as cerebroside sulfotransferase-deficient mice incapable of synthesising sulfatide. The sickle erythrocytes from mice and humans adhered at a greater extent and at higher shear stresses to activated endothelium than normal erythrocytes, and approximately 60% of the adhesion was prevented by the anti-sulfatide scFv. Similarly, the extent of adhesion of sulfatide-deficient erythrocytes was lower than normal erythrocytes. These findings suggest an important role for membrane sulfatide in sickle cell disease pathophysiology.
Imaging fibrin formation and platelet and endothelial cell activation in vivo
Authors: Furie Bruce , Bellido-Martin Lola , Chen Vivien , Jasuja Reema , Furie Barbara
Published: March 2011

Over the past six decades research employing in vitro assays has identified enzymes, cofactors, cell receptors and associated ligands important to the haemostatic process and its regulation. These studies have greatly advanced our understanding of the molecular and cellular bases of haemostasis and thrombosis. However, in vitro assays cannot simultaneously reproduce the interactions of all of the components of the haemostatic process that occur in vivo nor do they reflect the importance of haemodynamic factors resulting from blood flow. To overcome these limitations investigators have increasingly turned to animal models of haemostasis and thrombosis. In this article we describe some advances in the visualisation of platelet and endothelial cell activation and blood coagulation in vivo and review what we have learned from our intravital microscopy experiments using primarily the laser-induced injury model for thrombosis.
Neointima Formed by Arterial Smooth Muscle Cells Expressing Versican Variant V3 Is Resistant to Lipid and Macrophage Accumulation
Authors: Merrilees Mervyn J. , Beaumont Brent W. , Braun Kathleen R. , Thomas Anita C. , Kang Inkyung , Hinek Aleksander , Passi Alberto , Wight Thomas N.
Published: March 2011

Objective—

Extracellular matrix (ECM) of neointima formed following angioplasty contains elevated levels of versican, loosely arranged collagen, and fragmented deposits of elastin, features associated with lipid and macrophage accumulation. ECM with a low versican content, compact structure, and increased elastic fiber content can be achieved by expression of versican variant V3, which lacks chondroitin sulfate glycosaminoglycans. We hypothesized that V3-expressing arterial smooth muscle cells (ASMC) can be used to form a neointima resistant to lipid and macrophage accumulation associated with hypercholesterolemia.

Methods and Results—

ASMC transduced with V3 cDNA were seeded into ballooned rabbit carotid arteries, and animals were fed a chow diet for 4 weeks, followed by a cholesterol-enriched diet for 4 weeks, achieving plasma cholesterol levels of 20 to 25 mmol/L. V3 neointimae at 8 weeks were compact, multilayered, and elastin enriched. They were significantly thinner (57%) than control neointimae; contained significantly more elastin (118%), less collagen (22%), and less lipid (76%); and showed significantly reduced macrophage infiltration (85%). Mechanistic studies demonstrated that oxidized low-density lipoprotein stimulated the formation of a monocyte-binding ECM, which was inhibited in the presence of V3 expressing ASMC.

Conclusion—

These results demonstrate that expression of V3 in vessel wall creates an elastin-rich neointimal matrix that in the presence of hyperlipidemia is resistant to lipid deposition and macrophage accumulation.
Chronic Electrical Neuronal Stimulation Increases Cardiac Parasympathetic Tone by Eliciting Neurotrophic Effects
Authors: Rana Obaida R. , Saygili Erol , Gemein Christopher , Zink Matthias D.H. , Buhr Alexandra , Saygili Esra , Mischke Karl , Nolte Kay W. , Weis Joachim , Weber Christian , Marx Nikolaus , Schauerte Patrick
Published: March 2011

Rationale:

Recently, we provided a technique of chronic high-frequency electric stimulation (HFES) of the right inferior ganglionated plexus for ventricular rate control during atrial fibrillation in dogs and humans. In these experiments, we observed a decrease of the intrinsic ventricular rate during the first 4 to 5 months when HFES was intermittently shut off.

Objective:

We thus hypothesized that HFES might elicit trophic effects on cardiac neurons, which in turn increase baseline parasympathetic tone of the atrioventricular node.

Methods and Results:

In mongrel dogs atrial fibrillation was induced by rapid atrial pacing. Endocardial HFES of the right inferior ganglionated plexus, which contains abundant fibers to the atrioventricular node, was performed for 2 years. Sham-operated nonstimulated dogs served as control. In chronic neurostimulated dogs, we found an increased neuronal cell size accompanied by an increase of choline acetyltransferase and unchanged tyrosine hydroxylase protein expression as compared with unstimulated dogs. Moreover, β-nerve growth factor (NGF) and neurotrophin (NT)-3 were upregulated in chronically neurostimulated dogs. In vitro, HFES of cultured neurons of interatrial ganglionated plexus from adult rats increased neuronal growth accompanied by upregulation of NGF, NT-3, glial-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) expression. NGF was identified as the main growth-inducing factor, whereas NT-3 did not affect HFES-induced growth. However, NT-3 could be identified as an important acetylcholine-upregulating factor.

Conclusions:

HFES of cardiac neurons in vivo and in vitro causes neuronal cellular hypertrophy, which is mediated by NGF and boosters cellular function by NT-3–mediated acetylcholine upregulation. This knowledge may contribute to develop HFES techniques to augment cardiac parasympathetic tone.
Noninvasive Brain Stimulation May Improve Stroke-Related Dysphagia
Authors: Kumar Sandeep , Wagner Cynthia W. , Frayne Colleen , Zhu Lin , Selim Magdy , Feng Wuwei , Schlaug Gottfried
Published: March 2011

Background and Purpose—

Treatment options for stroke-related dysphagia are currently limited. In this study, we investigated whether noninvasive brain stimulation in combination with swallowing maneuvers facilitates swallowing recovery in dysphagic stroke patients during early stroke convalescence.

Methods—

Fourteen patients with subacute unilateral hemispheric infarction were randomized to anodal transcranial direct current stimulation (tDCS) versus sham stimulation to the sensorimotor cortical representation of swallowing in the unaffected hemisphere over the course of 5 consecutive days with concurrent standardized swallowing maneuvers. Severity of dysphagia was measured using a validated swallowing scale, Dysphagia Outcome and Severity scale, before the first and after the last session of tDCS or sham. The effect of tDCS was analyzed in a multivariate linear regression model using changes in Dysphagia Outcome and Severity Scale as the outcome variable after adjusting for the effects of other potential confounding variables such as the National Institutes of Health Stroke Scale and Dysphagia Outcome and Severity scale scores at baseline, acute ischemic lesion volumes, patient age, and time from stroke onset to stimulation.

Results—

Patients who received anodal tDCS gained 2.60 points of improvement in Dysphagia Outcome and Severity scale scores compared to patients in the sham stimulation group who showed an improvement of 1.25 points (
P
=0.019) after controlling for the effects of other aforementioned variables. Six out 7 (86%) patients in tDCS stimulation group gained at least 2 points of improvement compared with 3 out 7 (43%) patients in the sham group (
P
=0.107).

Conclusions—

Because brain stem swallowing centers have bilateral cortical innervations, measures that enhance cortical input and sensorimotor control of brain stem swallowing may be beneficial for dysphagia recovery.
Family History of Stroke Is an Independent Risk Factor for Lacunar Stroke Subtype With Asymptomatic Lacunar Infarcts at Younger Ages
Authors: Knottnerus Iris L.H. , Gielen Marij , Lodder Jan , Rouhl Rob P.W. , Staals Julie , Vlietinck Robert , van Oostenbrugge Robert J.
Published: March 2011

Background and Purpose—

Results from case-control and case-case studies indicate that a positive family history of stroke (FHstroke) is an independent risk factor for lacunar stroke. Different lacunar stroke phenotypes can be distinguished on the basis of the presence of asymptomatic lacunar infarcts (aLACs), ischemic white-matter lesions, or brain microbleeds. The aim of the present study was to determine whether familial aggregation of stroke was different for lacunar stroke phenotypes.

Methods—

In 157 patients with a first-ever lacunar stroke, a complete first-degree FHstroke was obtained by a standardized questionnaire and additional interview. Lacunar stroke patients were categorized successively into groups, depending on the presence of aLACs, ischemic white-matter lesions, and brain microbleeds on magnetic resonance imaging.

Results—

Fifty-two percent of patients reported a positive FHstroke in at least one of their first-degree relatives. In younger (<65 years) probands, a high frequency of parental FHstroke (59% versus 20%,
P
<0.01) in those with aLACs compared with probands without aLACs was found. In multivariate analysis, the strongest associations were found for parental FHstroke (odds ratio=6.46; 95% CI=1.96 to 21.33), maternal FHstroke (odds ratio=4.00; 95% CI=1.18 to 13.56), and paternal FHstroke (odds ratio=5.40; 95% CI=1.14 to 25.61).

Conclusions—

A family history of stroke might be an independent risk factor for the lacunar stroke phenotype with aLACs at younger ages, suggesting a role for genetic factors in this phenotype caused by diffuse vasculopathy.
In Vivo Real-Time Multiphoton Imaging of T Lymphocytes in the Mouse Brain After Experimental Stroke
Authors: Fumagalli Stefano , Coles Jonathan A. , Ejlerskov Patrick , Ortolano Fabrizio , Bushell Trevor J. , Brewer James M. , De Simoni Maria-Grazia , Dever Gary , Garside Paul , Maffia Pasquale , Carswell Hilary V.
Published: March 2011

Background and Purpose—

To gain a better understanding of T cell behavior after stroke, we have developed real-time in vivo brain imaging of T cells by multiphoton microscopy after middle cerebral artery occlusion.

Methods—

Adult male hCD2-GFP transgenic mice that exhibit green fluorescent protein-labeled T cells underwent permanent left distal middle cerebral artery occlusion by electrocoagulation (n=6) or sham surgery (n=6) and then multiphoton laser imaging 72 hours later.

Results—

Extravasated T cell number significantly increased after middle cerebral artery occlusion versus sham. Two T cell populations existed after middle cerebral artery occlusion, possibly driven by 2 T cell subpopulations; 1 had significantly lower and the other significantly higher track velocity and displacement rate than sham.

Conclusions—

The different motilities and behaviors of T cells observed using our imaging approach after stroke could reveal important mechanisms of immune surveillance for future therapeutic exploitations.
Partial Aortic Occlusion and Cerebral Venous Steal
Authors: Pranevicius Osvaldas , Pranevicius Mindaugas , Liebeskind David S.
Published: March 2011

Acute ischemic stroke therapy emphasizes early arterial clot lysis or removal. Partial aortic occlusion has recently emerged as an alternative hemodynamic approach to augment cerebral perfusion in acute ischemic stroke. The exact mechanism of cerebral flow augmentation with partial aortic occlusion remains unclear and may involve more than simple diversion of arterial blood flow from the lower body to cerebral collateral circulation. The cerebral venous steal hypothesis suggests that even a small increase in tissue pressure in the ischemic area will divert blood flow to surrounding regions with lesser tissue pressures. This may cause no-reflow (absence of flow after restoration of arterial patency) in the ischemic core and “luxury perfusion” in the surrounding regions. Such maldistribution may be reversed with increased venous pressure titrated to avoid changes in intracranial pressure. We propose that partial aortic occlusion enhances perfusion in the brain by offsetting cerebral venous steal. Partial aortic occlusion redistributes blood volume into the upper part of the body, manifested by an increase in central venous pressure. Increased venous pressure recruits the collapsed vascular network and, by eliminating cerebral venous steal, corrects perifocal perfusion maldistribution analogous to positive end-expiratory pressure recruitment of collapsed airways to decrease ventilation/perfusion mismatch in the lungs.
Screening for Right-to-Left Shunts With Contrast Transcranial Doppler in Hereditary Hemorrhagic Telangiectasia
Authors: Manawadu Dulka , Vethanayagam Dilini , Saqqur Maher , Derksen Carol , Choy Jonathan , Khan Khurshid
Published: March 2011

Background and Purpose—

Contrast transthoracic echocardiography (TTCE) is used to screen hereditary hemorrhagic telangiectasia (HHT) patients for right-to-left shunts (RLS) associated with increased stroke risk. We hypothesized that contrast transcranial Doppler (TCDc), shown to be highly sensitive for detecting RLS in patent foramen ovale, will be as comparable to TTCE for screening HHT patients.

Methods—

We compared TTCE and TCDc for detecting RLS in 12 patients with HHT who also underwent CT pulmonary studies to determine pulmonary arteriovenous malformation (PAVM) presence. The sensitivity and specificity of TTCE and TCDc in detecting PAVM were determined and the agreement between TTCE and TCDc in detecting RLS was assessed.

Results—

Both TTCE and TCDc had 100% sensitivity in detecting underlying PAVM; the specificity was 25% and 38%, respectively. The agreement in detecting RLS between TTCE and TCD was high (κ=0.76). TCD was well-tolerated with no immediate adverse or embolic events over the next 3 months.

Conclusions—

TCDc offers a simple office-based alternative to TTCE for screening RLS associated with PAVM in HHT patients.
Racialized Media Coverage of Minority Candidates in the 2008 Democratic Presidential Primary
Authors: McIlwain Charlton D.
Published: March 2011

This article investigates the prominence of racial content in newspaper stories about Barack Obama and three other candidates running in the 2008 Democratic Party presidential primary. Content analyses of stories appearing in six national newspapers sought to ascertain how frequent racial references appeared in news accounts of the presidential contest, how salient the racial content was, and what factors explained race-related coverage. Consistent with previous studies, the presence of one or more racial minorities in the stories increased the likelihood and presence of racial references found in the story. However, results challenge the conventional wisdom that racial content is salient enough to serve as a prominent racial cue activating readers’ or voters’ negative racial prejudices. This study finds that more than any other factor, journalists’ desire to heighten the election’s competitiveness influenced the presence and degree of racial content present in stories.
The Mobilized Voter: Portrayals of Electoral Participation in Print News Coverage of Campaign 2008
Authors: Jarvis Sharon E. , Han Soo-Hye
Published: March 2011

This study examines how electoral participation was portrayed in print news coverage of the 2008 American presidential election. Specifically, 2,241 instances of three terms— vote, voter, and voting—were subjected to quantitative and qualitative coding techniques and compared to a larger project that analyzed more than 26,000 instances of these terms in coverage of 15 presidential elections, 1948 to 2004. The findings show that print coverage of electoral participation in 2008 featured the lowest level of game framing, the second-highest level of mobilization efforts, the most positive tone, and the most mentions of electoral challenges of the past 60 years. The article interprets these trends in light of journalistic routines and the potential socialization effects of such coverage.
An evaluation of the effects of chronic diseases and health conditions on tobacco cessation
Authors: Bowden Dawn E , Barr Nikki , Rickert Shannon
Published: March 2011

Objective: This study examined the effects of chronic health conditions on tobacco cessation and participation in a follow-up assessment among 13,900 smokers in a telephone-based tobacco cessation programme.

Design: This study involved gathering data from individuals during pre- and post-intervention telephonic assessments following their decision to participate in the tobacco cessation wellness programme.

Setting: The study sample included participants from across the United States, with a large concentration living in the Midwestern region.

Method: The study sample was limited to participants who were eligible to receive three-month, six-month, and 12-month follow-up calls. Logistic regressions were used to allow an estimate of the impact of chronic conditions while holding constant other factors such as age, readiness, and confidence.

Results: The results suggest that the presence of certain chronic conditions was associated with a reduced likelihood of quitting smoking. The presence of chronic conditions did not influence the likelihood that participants completed the follow-up assessment. Interestingly, the effect of chronic conditions on cessation was only slightly higher than the impact of gender. The four-point difference warrants further investigation, especially considering the higher rates of depression in women.

Conclusion: This study supports prior research that the presence of one or more chronic conditions has a negative effect on the ability to cease tobacco use. More customized programmes are required to overcome the significant effect of gender, the presence of certain chronic conditions such as depression, and the impact of follow-up calls on cessation success.
Graphite fiber composites interlayered with single-walled carbon nanotubes
Authors: Kim H.S. , Hahn H.T.
Published: March 2011

A scalable processing method was used to fabricate graphite fiber composites with single-walled carbon nanotubes (SWCNTs) and the microstructures and properties of the fabricated laminates were investigated. SWCNTs were sprayed onto the surface of graphite/epoxy prepreg using an air spray. Interlaminar shear strength (ILSS) tests showed that the air spray processing had minimal effect on the quality of the laminates. Scanning electron microscopy (SEM) studies showed that SWCNTs are distributed uniformly in the plane of the laminate but not in the thickness direction due to low resin flow during cure. At high concentrations (>1.0 wt%), combination of a rather thick band of SWCNTs and low resin flow caused lack of resin inside of SWCNT bundles. The properties positively affected are in-plane shear strength, interlaminar fracture toughness (mode I), compressive strength, and electrical conductivity. Those properties showed improvement particularly when a lower concentration of SWCNTs was used. Fractography study using SEM showed altered crack propagation and crack bridging due to the presence of SWCNTs. The out-of-plane electrical conductivity was improved by 144% for 2 wt% SWCNT samples compared to samples without SWCNTs.
The Role of iNOS and PHOX in Periapical Bone Resorption
Authors: Silva M.J.B. , Sousa L.M.A. , Lara V.P.L. , Cardoso F.P. , Júnior G.M. , Totola A.H. , Caliari M.V. , Romero O.B. , Silva G.A.B. , Ribeiro-Sobrinho A.P. , Vieira L.Q.
Published: March 2011

Nitric oxide (NO) and reactive oxygen species (ROS) are key molecules in resistance to pathogens. Little is known about their role in pathogenesis of periapical lesions. To address this issue, we induced periapical lesions in mice lacking nitric oxide synthase (iNOS-/-) or phagocyte oxidase (PHOX-/-). iNOS-/- mice expressed higher levels of IL-1β, TNF-α, RANK, RANKL, and MCP-1 than C57BL/6 and PHOX-/-. Apical thickening of the periodontal ligament was also greater in iNOS-/- compared with other groups. Interestingly, ROS production did not interfere in periapical lesion progression, but seemed to be essential for the appearance of multinucleated TRAP-positive cells. Thus, periapical lesion progression in iNOS-/- was associated with an imbalance of pro-inflammatory cytokines (IL-1β and TNF-α), bone-resorptive modulators (RANK and RANKL), and MCP-1. We conclude that NO, but not ROS, controls progression of bone resorption in a murine experimental model of apical periodontitis.
Scientific Approaches to AIDS Prevention and Control in China
Authors: Teng T. , Shao Y.
Published: March 2011

The HIV epidemic in China started among intravenous drug users in the late 1980s. The second wave of the epidemic was caused by an outbreak in the paid plasma donors in central China in the mid-1990s. Sexually transmitted HIV cases have steadily increased and comprised more than half the reported HIV/AIDS infections since 2007. In the last 5 years, there has been a sharp increase of HIV infection in men who have sex with men. The HIV epidemic in China has expanded from high-risk groups to the general population and from rural regions to urban areas. This brief article discusses the history of HIV epidemics in China and the challenges facing the current AIDS control efforts in the country. It explains that only scientific approaches can sustain the national AIDS control programs and introduce the type of research needed to address those challenges. The selected research areas include molecular epidemiology, drug resistance surveillance, and the Chinese HIV vaccine research.
Overview of the Oral HIV/AIDS Research Alliance Program
Authors: Shiboski C.H. , Webster-Cyriaque J.Y. , Ghannoum M. , Greenspan J.S. , Dittmer D. ,   Oral HIV/AIDS Research Alliance, Subcommittee of the AIDS Clinical Trial Group
Published: March 2011

The Oral HIV/AIDS Research Alliance is part of the AIDS Clinical Trials Group, the largest HIV clinical trial organization in the world, and it is funded by the National Institute of Dental and Craniofacial Research, in collaboration with the National Institute of Allergy and Infectious Diseases. The alliance’s main objective is to investigate the oral complications associated with HIV/AIDS as the epidemic is evolving—in particular, the effects of potent antiretrovirals on the development of oral mucosal lesions and associated fungal and viral pathogens. Furthermore, oral fluids are being explored for their potential monitoring and diagnostic role with respect to HIV disease and coinfections. This article presents an overview of the alliance, its scientific agenda, and an outline of the novel interventional and noninterventional clinical studies ongoing and developing within the AIDS Clinical Trials Group infrastructure in the United States and internationally.
Plausibility of HIV-1 Infection of Oral Mucosal Epithelial Cells
Authors: Herzberg M.C. , Vacharaksa A. , Gebhard K.H. , Giacaman R.A. , Ross K.F.
Published: March 2011

The AIDS pandemic continues. Little is understood about how HIV gains access to permissive cells across mucosal surfaces, yet such knowledge is crucial to the development of successful topical anti-HIV-1 agents and mucosal vaccines. HIV-1 rapidly internalizes and integrates into the mucosal keratinocyte genome, and integrated copies of HIV-1 persist upon cell passage. The virus does not appear to replicate, and the infection may become latent. Interactions between HIV-1 and oral keratinocytes have been modeled in the context of key environmental factors, including putative copathogens and saliva. In keratinocytes, HIV-1 internalizes within minutes; in saliva, an infectious fraction escapes inactivation and is harbored and transferable to permissive target cells for up to 48 hours. When incubated with the common oral pathogen Porphyromonas gingivalis, CCR5− oral keratinocytes signal through protease-activated receptors and Toll-like receptors to induce expression of CCR5, which increases selective uptake of infectious R5-tropic HIV-1 into oral keratinocytes and transfer to permissive cells. Hence, oral keratinocytes—like squamous keratinocytes of other tissues—may be targets for low-level HIV-1 internalization and subsequent dissemination by transfer to permissive cells.
Candida-Host Interactions in HIV Disease
Authors: Fidel P.L.
Published: March 2011

Oropharyngeal candidiasis (OPC), caused primarily by Candida albicans, is the most common oral infection in HIV+ persons. Although Th1-type CD4+ T cells are the predominant host defense mechanism against OPC, CD8+ T cells and epithelial cells become important when blood CD4+ T cells are reduced below a protective threshold during progression to AIDS. In an early cross-sectional study, OPC+ tissue biopsied from HIV+ persons had an accumulation of activated memory CD8+ T cells at the oral epithelial–lamina propria interface, with reduced expression of the adhesion molecule E-cadherin, suggesting a protective role for CD8+ T cells but a dysfunction in the mucosal migration of the cells. In a subsequent 1-year longitudinal study, OPC− patients with high oral Candida colonization (indicative of a preclinical OPC condition), had higher numbers of CD8+ T cells distributed throughout the tissue, with normal E-cadherin expression. In OPC+ patients, where lack of CD8+ T cell migration was associated with reduced E-cadherin, subsequent evaluations following successful treatment of infection revealed normal E-cadherin expression and cellular distribution. Regarding epithelial cell responses, intact oral epithelial cells exhibit fungistatic activity via an acid-labile protein moiety. A proteomic analysis revealed that annexin A1 is a strong candidate for the effector moiety. The current hypothesis is that under reduced CD4+ T cells, HIV+ persons protected from OPC have CD8+ T cells that migrate to the site of a preclinical infection under normal expression of E-cadherin, whereas those with OPC have a transient reduction in E-cadherin that prohibits CD8+ T cells from migrating for effector function. Oral epithelial cells concomitantly function through annexin A1 to keep Candida in a commensal state but can easily be overwhelmed, thereby contributing to susceptibility to OPC.
Epithelial Cell Innate Response to Candida albicans
Authors: Naglik J.R. , Moyes D.
Published: March 2011

With the advent of treatments and diseases such as AIDS resulting in increasing numbers of patients with suppressed immune systems, fungal diseases are an escalating problem. Candida albicans is the most common of these fungal pathogens, causing infections in many of these patients. It is therefore important to understand how immunity to this fungus is regulated and how it might be manipulated. Although work has been done to identify the receptors, fungal moieties, and responses involved in anti- Candida immunity, most studies have investigated interactions with myeloid or lymphoid cells. Given that the first site of contact of C. albicans with its host is the mucosal epithelial surface, recent studies have begun to focus on interactions of C. albicans with this site. The results are startling yet in retrospect obvious, indicating that epithelial cells play an important role in these interactions, initiating responses and even providing a level of protection. These findings have obvious implications, not just for fungal pathogens, but also for identifying how host organisms can distinguish between commensal and pathogenic microbes. This review highlights some of these recent findings and discusses their importance in the wider context of infection and immunity.
Pediatric Oral HIV Research in the Developing World
Authors: Yengopal V. , Bhayat A. , Coogan M.
Published: March 2011

This article is a review of the literature between 2003 (since the last workshop) and April 2009 (Beijing workshop). It focuses on the prevalence of oral lesions associated with HIV infection, oral lesions as predictors of HIV infection, oral lesions as markers of the efficacy of highly active antiretroviral treatment and quality of life, caries risk, the management of oral lesions, and epidemiologic tests for clinical significance of oral lesions.
Kaposi Sarcoma–Associated Herpesvirus/Human Herpesvirus 8 and Kaposi Sarcoma
Authors: Martin J.N.
Published: March 2011

Kaposi sarcoma-associated herpesvirus (KSHV) was discovered in 1994 and is now known to be a necessary but not sufficient causative agent of Kaposi sarcoma. While KSHV is likely also the causative agent of primary effusion lymphoma and multicentric Castleman’s disease, its causal role has been refuted in the case of multiple myeloma, sarcoidosis, prostate cancer, and amyotrophic lateral sclerosis. The epidemiology of KSHV is both intriguing and challenging. Two epidemiologic findings are clear, but their explanation is unknown. The first is that KSHV is distributed disparately throughout the world, with the virus being common in the general population throughout Africa and the Middle East, but uncommon virtually everywhere else. The second is that even though the virus is uncommon in the general population in industrialized settings, it is disproportionately concentrated among homosexual men in these areas. KSHV has special importance to the dental profession because saliva is the body fluid that harbors it most commonly, although exactly in which ways saliva spreads the virus are not known.
HIV Transmission in the Dental Setting and the HIV-Infected Oral Health Care Professional
Authors: Flint S.R. , Croser D. , Reznik D. , Glick M. , Naidoo S. , Coogan M.
Published: March 2011

This workshop addressed two important issues: first, the global evidence of HIV transmission from health care provider to patient and from patient to health care provider in the general health care environment and the dental practice setting; second, in the era of highly active antiretroviral therapy, whether oral health care professionals living with HIV pose a risk of transmission to their patients and whether standard infection control is adequate to protect both the patient and the oral health care professional in dental practice. The workshop culminated in a general discussion and the formulation of a consensus statement from the participating delegates, representing more than 30 countries, on the criteria under which an HIV-infected oral health care professional might practice dentistry without putting patients at risk. This consensus statement, the Beijing Declaration, was agreed nem con.
Mechanisms of Viral Infections Associated with HIV
Authors: Tugizov S.M. , Webster-Cyriaque J.Y. , Syrianen S. , Chattopadyay A. , Sroussi H. , Zhang L. , Kaushal A.
Published: March 2011

HIV infection is commonly associated with activation and dissemination of several other viral pathogens, including herpes simplex virus 1/2, human cytomegalovirus, human herpesvirus 8, Epstein-Barr virus, Varicella Zoster virus, and human papillomavirus, which behave as opportunistic agents and cause various diseases in immunocompromised hosts. The increased frequency and severity of diseases caused by these viruses in HIV-infected individuals is due mainly to dysfunction of both the adaptive and innate immune responses to viral pathogens. In addition, molecular interactions between HIV and these opportunistic viruses are likely to play critical roles in the progression of disease, including neoplasia. This report reviews the critical aspects of HIV interaction with opportunistic viruses, including Epstein-Barr virus, human cytomegalovirus, herpes simplex virus, Varicella Zoster virus, human herpesvirus 8, and human papillomavirus.