bluuebunny/crossref_metadata_2025 huggingface dataset:
Epithelial Barriers in Homeostasis and Disease
Authors: Marchiando Amanda M. , Graham W. Vallen , Turner Jerrold R.
Published: January 2010

Epithelia form barriers that are essential to life. This is particularly true in the intestine, where the epithelial barrier supports nutrient and water transport while preventing microbial contamination of the interstitial tissues. Along with plasma membranes, the intercellular tight junction is the primary cellular determinant of epithelial barrier function. Disruption of tight junction structure, as a result of specific protein mutations or aberrant regulatory signals, can be both a cause and an effect of disease. Recent advances have provided new insights into the extracellular signals and intracellular mediators of tight junction regulation in disease states as well as into the interactions of intestinal barrier function with mucosal immune cells and luminal microbiota. In this review, we discuss the critical roles of the tight junction in health and explore the contributions of barrier dysfunction to disease pathogenesis.
Fibrogenic Reactions in Lung Disease
Authors: Araya Jun , Nishimura Stephen L.
Published: January 2010

Fibrogenic lung reactions occur as a common phenotype shared among disorders of heterogeneous etiologies. Even with a common etiology, the extent and pattern of fibrosis vary greatly among individuals, even within families, suggesting complex gene-environment interactions. The search for mechanisms shared among all fibrotic lung diseases would represent a major advance in the identification of therapeutic targets that could have a broad impact on lung health. Although it is difficult to grasp all of the complexities of the varied cell types and cytokine networks involved in lung fibrogenic responses, and to predict the biologic responses to the overexpression or deficiency of individual cytokines, a large body of evidence converges on a single common theme: the central importance of the transforming growth factor beta (TGF-β) pathway. Therapies that act upstream or downstream of TGF-β activation have the therapeutic potential to treat all fibrogenic responses in the lung.
Comparative structural and hemodynamic analysis of vascular trees
Authors: Yang J. , Yu L. X. , Rennie M. Y. , Sled J. G. , Henkelman R. M.
Published: January 2010

The availability of detailed three-dimensional images of vascular trees from mammalian organs provides a wealth of essential data for understanding the processes and mechanisms of vascular patterning. Using this detailed geometric data requires the ability to compare individual representations of vascular trees in statistically meaningful ways. This article provides some comparisons of geometry and also of simulated hemodynamics, enabling the identification of similarities and differences among 10 individual specimens (5 placenta specimens and 5 lung specimens). Similar comparisons made with a series of models (starting with the simplest and increasing in complexity) enable the identification of essential features that are needed to account for the patterns and function of vascular arborization.
Biaxial distension of precision-cut lung slices
Authors: Dassow C. , Wiechert L. , Martin C. , Schumann S. , Müller-Newen G. , Pack O. , Guttmann J. , Wall W. A. , Uhlig S.
Published: January 2010

The mechanical forces acting on lung parenchyma during (mechanical) ventilation and its (patho)physiological consequences are currently under intense scrutiny. Several in vivo and cell culture models have been developed to study the pulmonary responses to mechanical stretch. While providing extremely useful information, these models do also suffer from limitations in being either too complex for detailed mechanical or mechanistic studies, or in being devoid of the full complexity present in vivo (e.g., different cell types and interstitial matrix). Therefore in the present study it was our aim to develop a new model, based on the biaxial stretching of precision-cut lung slices (PCLS). Single PCLS were mounted on a thin and flexible carrier membrane of polydimethylsiloxane (PDMS) in a bioreactor, and the membrane was stretched by applying varying pressures under static conditions. Distension of the membrane-PCLS construct was modeled via finite element simulation. According to this analysis, lung tissue was stretched by up to 38% in the latitudinal and by up to 44% in the longitudinal direction, resulting in alveolar distension similar to what has been described in intact lungs. Stretch for 5 min led to increased cellular calcium levels. Lung slices were stretched dynamically with a frequency of 15/min for 4 h without causing cell injury {3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test; live/dead straining}. These findings suggest that stretching of PCLS on PDMS-membranes may represent a useful model to investigate lung stretch in intact lung tissue in vitro for several hours.
In vivo anti-inflammatory action of eugenol on lipopolysaccharide-induced lung injury
Authors: Magalhães Clarissa B. , Riva Douglas R. , DePaula Leonardo J. , Brando-Lima Aline , Koatz Vera Lúcia G. , Leal-Cardoso José Henrique , Zin Walter A. , Faffe Débora S.
Published: January 2010

Eugenol, a methoxyphenol component of clove oil, suppresses cyclooxygenase-2 expression, while eugenol dimers prevent nuclear factor-κB (NF-κB) activation and inflammatory cytokine expression in lipopolysaccharide-stimulated macrophages. Our aim was to examine the in vivo anti-inflammatory effects of eugenol. BALB/c mice were divided into four groups. Mice received saline [0.05 ml intratracheally (it), control (Ctrl) and eugenol (Eug) groups] or Escherichia coli LPS (10 μg it, LPS and LPSEug groups). After 6 h, mice received saline (0.2 ml ip, Ctrl and LPS groups) or eugenol (160 mg/kg ip, Eug and LPSEug groups). Twenty-four hours after LPS injection, pulmonary resistive (ΔP1) and viscoelastic (ΔP2) pressures, static elastance (Est), and viscoelastic component of elastance (ΔE) were measured. Lungs were prepared for histology. In parallel mice, bronchoalveolar lavage fluid was collected 24 h after LPS injection. TNF-α was determined by ELISA. Lung tissue expression of NF-κB was determined by EMSA. ΔP1, ΔP2, Est, and ΔE were significantly higher in the LPS group than in the other groups. LPS mice also showed significantly more alveolar collapse, collagen fibers, and neutrophil influx and higher TNF-α levels and NF-κB expression than the other groups. Eugenol treatment reduced LPS-induced lung inflammation, improving lung function. Our results suggest that eugenol exhibits in vivo anti-inflammatory action in LPS-induced lung injury.
Analyses of mouse breath with ion mobility spectrometry: a feasibility study
Authors: Vautz Wolfgang , Nolte Jürgen , Bufe Albrecht , Baumbach Jörg I. , Peters Marcus
Published: January 2010

Exhaled breath can provide comprehensive information about the metabolic state of the subject. Breath analysis carried out during animal experiments promises to increase the information obtained from a particular experiment significantly. This feasibility study should demonstrate the potential of ion mobility spectrometry for animal breath analysis, even for mice. In the framework of the feasibility study, an ion mobility spectrometer coupled with a multicapillary column for rapid preseparation was used to analyze the breath of orotracheally intubated spontaneously breathing mice during anesthesia for the very first time. The sampling procedure was validated successfully. Furthermore, the breath of four mice (2 healthy control mice, 2 with allergic airway inflammation) was analyzed. Twelve peaks were identified directly by comparison with a database. Additional mass spectrometric analyses were carried out for validation and for identification of unknown signals. Significantly different patterns of metabolites were detected in healthy mice compared with asthmatic mice, thus demonstrating the feasibility of analyzing mouse breath with ion mobility spectrometry. However, further investigations including a higher animal number for validation and identification of unknown signals are needed. Nevertheless, the results of the study demonstrate that the method is capable of rapid analyses of the breath of mice, thus significantly increasing the information obtained from each particular animal experiment.
Contributions of central and peripheral chemoreceptors to the ventilatory response to CO2/H+
Authors: Forster H. V. , Smith C. A.
Published: January 2010

The major objective of this review is to evaluate existing information and reach conclusions regarding whether there is interaction between Pco2/H+ stimulation of carotid (peripheral) and intracranial (central) chemoreceptors. Interaction is defined as a ventilatory response to simultaneous changes in the degree of Pco2/H+ stimulation of both chemoreceptors that is greater (hyperadditive) or less (hypoadditive) than the sum of the responses when stimulation of each set of chemoreceptors is individually altered. Simple summation of the simultaneous changes in stimuli results in no interaction (i.e., additive interaction). Knowledge of the nature of central/peripheral interaction is crucial for determining the physiological significance of newer models of ventilatory control based on recent neuroanatomic observations of the circuitry of key elements of the ventilatory control system. In this review, we will propose that these two sets of receptors are not functionally separate but rather that they are dependent on one another such that the sensitivity of the medullary chemoreceptors is critically determined by input from the peripheral chemoreceptors and possibly other breathing-related reflex afferents as well. The short format of this minireview demands that we be somewhat selective in developing our ideas. We will briefly discuss the limitations of experiments used to study CO2/H+ sensitivity and interaction to date, traditional views of the relative contributions of peripheral and central chemoreceptors to CO2/H+ sensitivity, the evidence for and against different types of interaction, and the effect of tonic carotid chemoreceptor afferent activity on central control mechanisms.
Concentric muscle contractions before static stretching minimize, but do not remove, stretch-induced force deficits
Authors: Kay Anthony D. , Blazevich Anthony J.
Published: January 2010

The effects of concentric contractions and passive stretching on musculotendinous stiffness and muscle activity were studied in 18 healthy human volunteers. Passive and concentric plantar flexor joint moment data were recorded on an isokinetic dynamometer with simultaneous electromyogram (EMG) monitoring of the triceps surae, real-time motion analysis of the lower leg, and ultrasound imaging of the Achilles-medial gastrocnemius muscle-tendon junction. The subjects then performed six 8-s ramped maximal voluntary concentric contractions before repeating both the passive and concentric trials. Concentric moment was significantly reduced (6.6%; P < 0.01), which was accompanied by, and correlated with ( r = 0.60–0.94; P < 0.05), significant reductions in peak triceps surae EMG amplitude (10.2%; P < 0.01). Achilles tendon stiffness was significantly reduced (11.7%; P < 0.01), but no change in gastrocnemius medialis muscle operating length was detected. The subjects then performed three 60-s static plantar flexor stretches before being retested 2 and 30 min poststretch. A further reduction in concentric joint moment (5.8%; P < 0.01) was detected poststretch at 90% of range of motion, with no decrease in muscle activity or Achilles tendon stiffness, but a significant increase in muscle operating length and decrease in tendon length was apparent at this range of motion ( P < 0.05). Thirty minutes after stretching, muscle activity significantly recovered to pre-maximal voluntary concentric contractions levels, whereas concentric moment and Achilles tendon stiffness remained depressed. These data show that the performance of maximal concentric contractions can substantially reduce neuromuscular activity and muscle force, but this does not prevent a further stretch-induced loss in active plantar flexor joint moment. Importantly, the different temporal changes in EMG and concentric joint moment indicate that a muscle-based mechanism was likely responsible for the force losses poststretch.
Sleep Dysfunction in Japanese Patients with Gastroesophageal Reflux Disease: Prevalence, Risk Factors, and Efficacy of Rabeprazole
Authors: Fujiwara Yasuhiro , Kohata Yukie , Kaji Makiko , Nebiki Hiroko , Yamasaki Tomoaki , Sasaki Eiji , Hayakawa Tsuyoshi , Machida Hirohisa , Tanigawa Tetsuya , Watanabe Kenji , Watanabe Toshio , Tominaga Kazunari , Arakawa Tetsuo
Published: January 2010

Background and Aim: Several studies performed in Western countries demonstrate the association between sleep dysfunction and gastroesophageal reflux disease (GERD), especially when nighttime heartburn is present. The purpose of this study was to examine the prevalence and risk factors of sleep dysfunction, and the effect of rabeprazole on reflux symptoms and sleep dysfunction in Japanese GERD patients. Methods: A total of 134 GERD patients, including 82 patients with non-erosive reflux disease (NERD), were enrolled. Patients received rabeprazole 10 mg daily for 8 weeks. Patients were asked to complete both a frequency scale for symptoms of GERD (FSSG) questionnaire and a Pittsburgh Sleep Quality Index (PSQI) questionnaire at baseline and 8 weeks after treatment. Results: Sleep dysfunction defined as a PSQI score >5.5 was found in 70 (52.2%) of the GERD patients. NERD was significantly associated with sleep dysfunction compared to erosive reflux disease (OR 2.18, 95% CI 1.05–4.53). However, other factors, including nighttime heartburn, were not associated with sleep dysfunction. Rabeprazole treatment significantly decreased both the FSSG and the PSQI score. Conclusion: The prevalence of sleep dysfunction was high among GERD patients. NERD was identified as a risk factor for sleep dysfunction. Use of a proton-pump inhibitor led to an effective decrease in sleep dysfunction. These results suggest a different pathogenesis of sleep dysfunction in Japanese GERD patients compared to GERD patients in Western countries. However, acid plays an important role in sleep dysfunction in all patients with GERD.
Multiple Intraluminal Impedance Measurement and Manometry in the Jejunum of Healthy Subjects: A New Tool for Diagnosis of Small Bowel Motility
Authors: Seidl Holger , Gundling Felix , Pehl Christian , Kissler Susan , Schepp Wolfgang , Schmidt Thomas
Published: January 2010

Background: The relationships between contractile activity and transport of intraluminal contents in the human small intestine are not well understood. Aim: To study both phenomena by combined measurements of intraluminal impedance and pressurein the jejunum of healthy subjects. Methods: 12 healthy volunteers (m 4, f 8), mean age 32.3 years (24–49 years), underwent jejunal combined impedance/manometry recordings (six channels at 2-cm intervals). Fasting (one MMC cycle) and postprandial motility were recorded. Results: Intestinal transport differed with the phases of motility. No transport was seen in phase I, regular bolus transport occurred during phase III. The longest duration of transport was observed in late phase II preceding phase III. Irregular and intermittent bolus transport occurred during early phase II and in the postprandial period. Three types of relationship between contractions and bolus transport were identified: transport with single contractions or migrating clustered contractions and transport without contractile activity. The frequency of these events differed with the direction of bolus transport, and a relationship between propagation velocity and bolus presence time was established. Conclusion: Combined simultaneous measurement of intraluminal impedance and manometry is a promising new method to elucidate the relationships between bolus transport and contractile activity in the human small bowel.
Marginal Growth Increase, Altered Bone Quality and Polycystic Ovaries in Female Prepubertal Rats after Treatment with the Aromatase Inhibitor Exemestane
Authors: van Gool Sandy A. , Wit Jan M. , De Schutter Tineke , De Clerck Nora , Postnov Andreï A. , Kremer Hovinga Sandra , van Doorn Jaap , Veiga Sergio J. , Garcia-Segura Luis Miguel , Karperien Marcel
Published: January 2010

Background: Aromatase inhibition has been proposed as a potential approach for growth enhancement in children with short stature, but detailed animal studies are lacking. Aim: To assess the effect and potential adverse effects of aromatase inhibition on growth in female rats. Methods: Prepubertal Wistar rats received intramuscular injections with placebo or the aromatase inhibitor exemestane at a dose of 10, 30 or 100 mg/kg/week (E10, E30, E100) for 3 weeks. A control group was ovariectomized (OVX). Weight and length gain, tibia and femur length, growth plate width, organ weights, insulin-like growth factor I (IGF-I) levels, and histology of the ovaries, uterus and brain were analyzed. X-ray microtomography of femora was performed. Results: E100 significantly increased weight gain and growth plate width, but less prominently than OVX. Trabecular number and thickness were decreased in E100 and OVX in the metaphysis and epiphysis. E100 significantly decreased ovarian weight and multiple cysts were seen upon histological evaluation. No significant effects were found on IGF-I levels and brain morphology in E100. E10 and E30 had no effects on growth. Conclusion: A high dose of exemestane marginally increases axial and appendicular growth in female rats, at the expense of osteopenia and polycystic ovaries.
Disorder in the Serotonergic System due to Tryptophan Hydroxylation Impairment: A Cause of Hypothalamic Syndrome?
Authors: Schott D.A. , Nicolai J. , de Vries J.E. , Keularts I.M.L.W. , Rubio-Gozalbo M.E. , Gerver W.J.M.
Published: January 2010

Background: The hypothalamus regulates basic homeostasis such as appetite, circadian rhythm, autonomic and pituitary functions. Dysregulation in these functions results in the hypothalamic syndrome, a rare disorder of various origins. Since serotonin (5-HT) modulates most of the above-mentioned homeostasis, a defect in the serotonergic system can possibly participate in this syndrome. Methods: We describe a girl suffering from hypothalamic syndrome with a decreased concentration of 5-hydroxytryptophan (5-HTP) and a normal level of tryptophan in the cerebrospinal fluid (CSF) suggesting a functional defect in tryptophan hydroxylase (TPH). TPH is a rate-limiting enzyme in the synthesis of the neurotransmitter 5-HT. Results: Therapeutic intervention with 5-HTP, carbidopa and a specific serotonin reuptake inhibitor significantly improved her clinical symptoms and caused biochemical normalisation of neurotransmitters. Conclusion: The girl described had the typical symptoms of a hypothalamic disorder and a defective serotonergic metabolism, a relationship which has not been reported before. Therapeutic interventions to restore 5-HT metabolism resulted in clinical improvement. We suggest that investigation of 5-HT metabolism in CSF of patients with this rare disorder is included in the aetiological work-up.
Effect of Intravenous Tirofiban and Aspirin in Reducing Short-Term and Long-Term Neurologic Deficit in Patients with Ischemic Stroke: A Double-Blind Randomized Trial
Authors: Torgano G. , Zecca B. , Monzani V. , Maestroni A. , Rossi P. , Cazzaniga M. , Manganaro D. , Boiti C. , Zilioli E. , Borutti G. , Falaschi F. , Mandelli C.
Published: January 2010

Background: Thrombolysis with rt-PA is the only approved pharmacological therapy for acute ischemic stroke presently administrable in a 3-hour window (very recently extended to 4.5 h). After this time, the choice is limited to endovascular treatment and antiplatelet drugs, mainly aspirin (ASA), the efficacy of which in the acute phase of stroke has poorly been evaluated. We compared the efficacy of tirofiban, a GP-IIb/IIIa inhibitor, and ASA, with both drugs being administered within 6 h. Methods: 150 patients were randomly assigned to treatment with tirofiban or ASA, both given for 3 days in a double-blind regimen. Major inclusion criteria were stroke onset within 6 h and a baseline National Institute of Health Stroke Scale (NIHSS) score of 5–25. Outcome variables were the proportion of patients with a NIHSS score reduction of ≧4 points after 72 h, and the proportion of patients with an mRS score of 0–1 at 3 months. Results: The trial, originally planned to enroll 300 patients, was halted after enrollment of 150 patients at interim analysis due to the lack of a trend difference between the 2 treatment groups. Neurological improvement at 72 h was observed in 56% of the patients in each group. At the 3-month follow-up, minimal or absent disability was seen in 45% of the patients in the tirofiban group and 53% in the ASA group; these differences were not statistically significant. Three-month mortality was the same in both groups (10.6%); the rates of symptomatic intracranial hemorrhage were 1% (tirofiban) and 4% (ASA). Conclusion: In spite of the fact that the null hypothesis was not supported by our data, we found results supporting the safety (and potential efficacy) of ASA and tirofiban when used in the first hours of acute ischemic stroke. However, this needs to be confirmed by further studies.
Potential Predictive Markers in Protocol Biopsies for Premature Renal Graft Loss
Authors: Matl Ivo , Hribova Petra , Honsova Eva , Brabcova Irena , Viklicky Ondrej
Published: January 2010

Background/Aims: Protocol biopsies offer new possibilities to predict kidney allograft outcome. The aim of this study was to find clinical, laboratory, morphological and molecular predictors of short-term renal graft survival. Methods: Three-month protocol kidney graft biopsy was carried out on 257 patients. The real-time RT-PCR was used to identify intragraft mRNA expression of several cytokines and chemokines and predictive statistics was performed to find markers connected with the risk of premature graft failure. Results: Compared to patients with normal morphology at 3 months, patients with subclinical rejection including borderline changes had experienced more frequent (p < 0.001) acute rejections before 3-month biopsy, serum creatinine ≧170 µmol/l (p < 0.01), and higher intrarenal expression of RANTES, IP-10 (p < 0.001), C3, CD3, IgJ (p < 0.01) and CD20 (p < 0.05). There was a significant correlation between subclinical rejection and the occurrence of late acute rejection and graft failure at the first year after transplantation. Moreover, higher RANTES and IP-10 expressions in subclinical rejection predicted graft loss at one year after transplantation in the univariate analysis. Conclusions: Patients with subclinical rejection including borderline changes in 3-month biopsy and particularly those with higher intrarenal expression of RANTES and IP-10 mRNA were found to be at risk for premature kidney graft loss.
Genetic Variations in the Sodium Balance-Regulating Genes ENaC, NEDD4L, NDFIP2 and USP2 Influence Blood Pressure and Hypertension
Authors: Jin Hyun-Seok , Hong Kyung-Won , Lim Ji-Eun , Hwang Sue-Yun , Lee Sang-Ho , Shin Chol , Park Hun Kuk , Oh Bermseok
Published: January 2010

Background/Aims: In humans, the kidneys regulate blood pressure by balancing sodium concentrations. Fine-tuning of renal sodium reabsorption and excretion depends on the epithelial sodium channel protein (ENaC: protein complex of SCNN1A, SCNN1B, and SCNN1G). The surface expression of ENaC components is directed by the ubiquitination of ENaC by NEDD4L, an ENaC-specific E3 ubiquitin ligase, and is regulated by the deubiquitination of ENaC by USP2. The activity of NEDD4L in turn is regulated by phosphorylation by SGK1 and also through interaction with NDFIP2. Methods: We analyzed 91 SNPs in 7 genes using the genotype data of 8,842 individuals from the Korea Association REsource subject pool for their correlation with blood pressure and hypertension. Results: 25 SNPs in the SCNN1A, SCNN1B, SCNN1G, NEDD4L, NDFIP2, and USP2 loci were found to be associated with blood pressure. An additional hypertension case-control study identified 13 SNPs in SCNN1B, SCNN1G, and NEDD4L that were linked to hypertension. Conclusion: These results support our hypothesis that individual variations in blood pressure are attributed to variants of the genes that regulate renal sodium reabsorption and excretion. Our data also suggest that it would be meaningful to investigate the role of NEDD4L-mediated ubiquitination in the pathogenesis of hypertension.
Population-Based Genetic Screening for Cystic Fibrosis: Attitudes and Outcomes
Authors: Ioannou L. , Massie J. , Collins V. , McClaren B. , Delatycki M.B.
Published: January 2010

A population-based cystic fibrosis (CF) carrier screening program was introduced in Victoria, Australia in 2006, and was offered to couples planning a pregnancy or in early pregnancy for a fee. Individuals received pre-test advice from their doctor and through a brochure. Carriers identified received genetic counseling. The aim of this study was to assess the attitudes of people undertaking screening. Between January 2006 and June 2008 all carriers (n = 79) and a randomly selected cohort of non-carriers (n = 162) were invited to participate. A purpose-designed questionnaire explored the following domains: knowledge, recollection and meaning of carrier status, reasons for having screening, anxiety and communication of results to family members. Forty-seven carriers (62%) and 65 non-carriers (41%) returned the questionnaire. Most participants were female (97%) aged 35–39 (46%). The main reasons for choosing screening were the perception of CF as a severe condition and a doctor’s recommendation. All carriers correctly recalled their carrier status and the risk of having a child with CF, while 3 non-carriers (4.7%) were unsure of their carrier status and 12 (22%) incorrectly recalled their residual risk. Carriers answered the knowledge questions correctly more often than non-carriers. There was no difference in anxiety between carriers and non-carriers. The majority of carriers informed relatives of their increased risk of being a carrier. We conclude that participants’ attitude towards carrier screening for CF was generally very positive. Our model of screening could be applied on a larger scale.
Long-Term Culture and Transplantation of Spermatogonial Stem Cells from BALB/c Mice
Authors: Shen Fujin , Zhang Ci , Zheng Hongyun , Xiong Yunhe , Wang Xi , Liao Wenbiao , Du Xianjin , Yang Sixing , Wang Linglong
Published: January 2010

Development of a culture system that supports self-renewal and proliferation of spermatogonial stem cells (SSCs) is enormously valuable for experimental research and potential treatment for male infertility. Although several research groups had reported their successes in SSC isolation and culture, the two current accepted culture systems are different in cell enrichment methods, serum and growth factors. Previous researches also indicated SSCs from different mouse strains required different culture conditions. Here we report for the first time that SSCs from BALB/c mice could be cultured in an improved culture system for 3 months. The modified culture system consisted of an improved enzymatic procedure, the enrichment of undifferentiated spermatogonia by differential adherence selection of isolated SSCs, mouse embryonic fibroblast feeder cells, StemPro-34 SFM medium supplemented with glial cell line-derived neurotrophic factor (GDNF), basic fibroblast growth factor and GDNF-family receptor α1 (GFRα1). The improved digestion method increased the viability and enrichment efficiency of isolated testis cells. Furthermore, basal culture medium with 10% fetal bovine serum as selected medium could increase the number of germ cell colonies in the initiation stage of culture. Cultured SSCs were characterized morphologically and formed typical colonies. Immunocytochemical staining and RT-PCR showed that cultured SSCs expressed Oct-4, GFRα1, Sox2 and several other special genes resembling undifferentiated spermatogonia. Spermatogonia transplantation further confirmed that cultured SSCs were functionally normal and could restore complete spermatogenesis. The culture methods described here could serve as a paradigm to establish conditions for the culture of SSCs from other species, allowing identification of universal factors necessary for proliferation of SSCs.
Public and Biobank Participant Attitudes toward Genetic Research Participation and Data Sharing
Authors: Lemke A.A. , Wolf W.A. , Hebert-Beirne J. , Smith M.E.
Published: January 2010

Research assessing attitudes toward consent processes for high-throughput genomic-wide technologies and widespread sharing of data is limited. In order to develop a better understanding of stakeholder views toward these issues, this cross-sectional study assessed public and biorepository participant attitudes toward research participation and sharing of genetic research data. Forty-nine individuals participated in 6 focus groups; 28 in 3 public focus groups and 21 in 3 NUgene biorepository participant focus groups. In the public focus groups, 75% of participants were women, 75% had some college education or more, 46% were African-American and 29% were Hispanic. In the NUgene focus groups, 67% of participants were women, 95% had some college education or more, and the majority (76%) of participants was Caucasian. Five major themes were identified in the focus group data: (a) a wide spectrum of understanding of genetic research; (b) pros and cons of participation in genetic research; (c) influence of credibility and trust of the research institution; (d) concerns about sharing genetic research data and need for transparency in the Policy for Sharing of Data in National Institutes of Health-Supported or Conducted Genome-Wide Association Studies; (e) a need for more information and education about genetic research. In order to increase public understanding and address potential concerns about genetic research, future efforts should be aimed at involving the public in genetic research policy development and in identifying or developing appropriate educational strategies to meet the public’s needs.
Strain Echocardiography and Wall Motion Score Index Predicts Final Infarct Size in Patients With Non–ST-Segment–Elevation Myocardial Infarction
Authors: Eek Christian , Grenne Bj�rnar , Brunvand Harald , Aakhus Svend , Endresen Knut , Hol Per K. , Smith Hans-J�rgen , Smiseth Otto A. , Edvardsen Thor , Skulstad Helge
Published: January 2010

Background—

Infarct size is a strong predictor of mortality and major adverse cardiovascular events after myocardial infarction. Acute reperfusion therapy limits infarct size and improves survival, but its use has been confined to patients with ST-segment–elevation myocardial infarction. The purpose of this study was to assess the relationship between echocardiographic parameters of left ventricular (LV) systolic function obtained before revascularization and final infarct size in patients with non–ST-segment–elevation myocardial infarction, as well as the ability of these parameters to identify patients with substantial infarction.

Methods and Results—

Sixty-one patients with non–ST-segment–elevation myocardial infarction were examined by echocardiography immediately before revascularization, 2.1�0.6 days after hospitalization. LV systolic function was assessed by ejection fraction, wall motion score index, and circumferential, longitudinal, and radial strain in a 16-segment LV model. Global strain represents average segmental strain values. Infarct size was assessed after 9�3 months by late-enhancement MRI, as a percentage of total LV myocardial volume. A good correlation was found between infarct size and wall motion score index (
r
=0.74,
P
<0.001) and global longitudinal strain (
r
=0.68,
P
<0.001). Global longitudinal strain >−13.8% and wall motion score index >1.30 accurately identified patients with substantial infarction (≥12% of myocardium, n=13; area under the receiver operator curve, 0.95 and 0.92, respectively).

Conclusions—

Echocardiographic parameters of LV systolic function correlate to infarct size in patients with non–ST-segment–elevation myocardial infarction. Global longitudinal strain and wall motion score index are both excellent parameters to identify patients with substantial myocardial infarction, who may benefit from urgent reperfusion therapy.
Dissociation of Obstructive Sleep Apnea From Hypersomnolence and Obesity in Patients With Stroke
Authors: Arzt Michael , Young Terry , Peppard Paul E. , Finn Laurel , Ryan Clodagh M. , Bayley Mark , Bradley T. Douglas
Published: January 2010

Background and Purpose—

Obstructive sleep apnea (OSA) is seldom considered in the diagnostic investigation in the poststroke period although it is a stroke risk factor and has adverse prognostic implications after stroke. One reason might be that widely used clinical criteria for detection of OSA in the general community are not applicable in patients with stroke. We hypothesized that patients with stroke report less sleepiness and are less obese than subjects from a community sample with the same severity of OSA.

Methods—

We performed polysomnography in 96 consecutive patients with stroke admitted to a stroke rehabilitation unit and in a community sample of 1093 subjects without a history of stroke. We compared the degrees of subjective sleepiness assessed by the Epworth Sleepiness Scale and body mass index between the 2 samples according to OSA categories assessed by the frequency of apneas and hypopneas per hour of sleep (<5, no OSA; 5 to <15 mild OSA; and ≥15, moderate to severe OSA).

Results—

Compared with the community sample, patients with stroke with OSA had significantly lower Epworth Sleepiness Scale scores and body mass index for mild OSA (Epworth Sleepiness Scale 9.3±0.3 versus 5.6±0.5,
P
<0.001 and body mass index 33.1±0.5 versus 28.5±1.1,
P
<0.048) and for moderate to severe OSA (Epworth Sleepiness Scale 9.7±0.4 versus 7.1±0.9,
P
=0.043 and body mass index 36.4±0.8 versus 27.2±0.8 kg/m
2
,
P
<0.025).

Conclusions—

For a given severity of OSA, patients with stroke had less daytime sleepiness and lower body mass index than subjects without stroke. These factors may make the diagnosis of OSA elusive in the poststroke period and preclude many such patients from the potential benefits of OSA therapy.
Neuroglobin Expression in Ischemic Stroke
Authors: Jin Kunlin , Mao Ying , Mao Xiao , Xie Lin , Greenberg David A.
Published: January 2010

Background and Purpose—

We investigated whether neuroglobin, a neuronal protein that protects neurons from hypoxic–ischemic injury, is upregulated in ischemic stroke.

Methods—

Neuroglobin immunoreactivity was measured in brain tissue from control subjects and patients with ischemic stroke.

Results—

Neuroglobin was detected in several brain areas, and its expression was increased in the cortical peri-infarct region after stroke.

Conclusions—

Ischemic stroke increases expression of the neuroprotective protein neuroglobin, suggesting neuroglobin may represent a novel target for stroke therapy.
MRI Perfusion Maps in Acute Stroke Validated With 15O-Water Positron Emission Tomography
Authors: Zaro-Weber Olivier , Moeller-Hartmann Walter , Heiss Wolf-Dieter , Sobesky Jan
Published: January 2010

Background and Purpose—

Perfusion-weighted imaging maps are used to identify hypoperfusion in acute ischemic stroke. We evaluated maps of cerebral blood flow (CBF), cerebral blood volume, mean transit time, and time to peak (TTP) in acute stroke by comparison with positron emission tomography.

Methods—

Perfusion-weighted imaging and positron emission tomography were performed in 26 patients with acute ischemic stroke (median 18.5 hours after stroke onset, 65 minutes between MRI and positron emission tomography). The perfusion-weighted imaging-derived maps of CBF, cerebral blood volume, mean transit time, and TTP delay were compared with quantitative positron emission tomography CBF. A receiver-operating characteristic curve analysis identified the best perfusion-weighted imaging map and threshold to identify hypoperfusion <20 mL/100 g/min, a widely used measure of penumbral flow.

Results—

Individual regression analysis of positron emission tomography CBF and perfusion-weighted imaging values were strong for CBF and TTP delay and weaker for mean transit time and cerebral blood volume, but the pooled analysis showed a large variance. Receiver-operating characteristic curve analysis identified TTP and CBF maps as most predictive (median area under the curve=0.94 and 0.93). Penumbral flow thresholds were <21.7 mL/100 g/min (CBF), <1.5 mL/100 g (cerebral blood volume), >5.3 seconds (mean transit time), and >4.2 seconds (TTP). TTP and CBF maps reached sensitivity/specificity values of 91%/82% and 89%/87%.

Conclusion—

In our sample, maps of CBF, TTP, and mean transit time yielded a good estimate of penumbral flow. The performance of TTP maps was equivalent to deconvolution techniques using an arterial input function. For all maps, the application of a predefined threshold is mandatory and calibration studies will enhance their use in acute stroke therapy as well as in clinical stroke trials.
Combination of NEP 1-40 Treatment and Motor Training Enhances Behavioral Recovery After a Focal Cortical Infarct in Rats
Authors: Fang Pei-chun , Barbay Scott , Plautz Erik J. , Hoover Erica , Strittmatter Stephen M. , Nudo Randolph J.
Published: January 2010

Background and Purpose—

Although myelin-associated neurite outgrowth disinhibitors have shown promise in restoring motor function after stroke, their interactive effects with motor training have rarely been investigated. The present study examined whether a combinatorial treatment (NEP 1-40+motor rehabilitation) is more effective than either treatment alone in promoting motor recovery after focal ischemic injury.

Methods—

Adult rats were assigned to one of 3 treatment groups (infarct/NEP 1-40+motor training, infarct/NEP 1-40 only, infarct/motor training only) and 2 control groups (infarct/no treatment, intact/no treatment). A focal ischemic infarct was induced by microinjecting endothelin-1 into the motor cortex. Therapeutic treatments were initiated 1 week postinfarct and included intraventricular infusion of the pharmacological agent NEP 1-40 and motor training (skilled reach task). Behavioral assessments on skilled reach, foot fault, and cylinder tests were conducted before the infarct and for 5 weeks postinfarct.

Results—

Rats demonstrated significant forelimb impairment on skilled reach and foot fault tests after the infarct. Although all infarct groups improved over time, motor training alone and NEP 1-40 alone facilitated recovery on the skilled reach task at the end of treatment Weeks 2 and 4, respectively. However, only NEP 1-40 paired with motor training facilitated recovery after 1 week of treatment in addition to treatment at Weeks 2 and 4. Finally, only the NEP 1-40+motor training group maintained a performance level equivalent to that of the intact group over the entire period of posttreatment assessment.

Conclusions—

This study suggests that behavioral training interacts with the effects of the axonal growth promoter, NEP 1-40, and may accelerate behavioral recovery after focal cortical ischemia.
Human Neural Stem Cell Grafts Modify Microglial Response and Enhance Axonal Sprouting in Neonatal Hypoxic–Ischemic Brain Injury
Authors: Daadi Marcel M. , Davis Alexis S. , Arac Ahmet , Li Zongjin , Maag Anne-Lise , Bhatnagar Rishi , Jiang Kewen , Sun Guohua , Wu Joseph C. , Steinberg Gary K.
Published: January 2010

Background and Purpose—

Hypoxic–ischemic (HI) brain injury in newborn infants represents a major cause of cerebral palsy, development delay, and epilepsy. Stem cell-based therapy has the potential to rescue and replace the ischemic tissue caused by HI and to restore function. However, the mechanisms by which stem cell transplants induce functional recovery are yet to be elucidated. In the present study, we sought to investigate the efficacy of human neural stem cells derived from human embryonic stem cells in a rat model of neonatal HI and the mechanisms enhancing brain repair.

Methods—

The human neural stem cells were genetically engineered for in vivo molecular imaging and for postmortem histological tracking. Twenty-four hours after the induction of HI, animals were grafted with human neural stem cells into the forebrain. Motor behavioral tests were performed the fourth week after transplantation. We used immunocytochemistry and neuroanatomical tracing to analyze neural differentiation, axonal sprouting, and microglia response. Treatment-induced changes in gene expression were investigated by microarray and quantitative polymerase chain reaction.

Results—

Bioluminescence imaging permitted real time longitudinal tracking of grafted human neural stem cells. HI transplanted animals significantly improved in their use of the contralateral impeded forelimb and in the Rotorod test. The grafts showed good survival, dispersion, and differentiation. We observed an increase of uniformly distributed microglia cells in the grafted side. Anterograde neuroanatomical tracing demonstrated significant contralesional sprouting. Microarray analysis revealed upregulation of genes involved in neurogenesis, gliogenesis, and neurotrophic support.

Conclusions—

These results suggest that human neural stem cell transplants enhance endogenous brain repair through multiple modalities in response to HI.
Advances in Imaging 2009
Authors: Sorensen A. Gregory , Heiss Wolf-Dieter
Published: January 2010

Imaging remains a mainstay of stroke diagnosis and treatment. 2009 brought much that was new: increased scrutiny of the safety of imaging; evidence of improved technical capabilities of imaging; new findings based on imaging; and as a result of the above, evidence that the field has definite needs. We will briefly cover each of these in turn.
A New Statistical Modeling Approach to Ocean Front Detection from SST Satellite Images
Authors: Hopkins Jo , Challenor Peter , Shaw Andrew G. P.
Published: January 2010

Ocean fronts are narrow zones of intense dynamic activity that play an important role in global ocean–atmosphere interactions. Owing to their highly variable nature, both in space and time, they are notoriously difficult features to adequately sample using traditional in situ techniques. In this paper, the authors propose a new statistical modeling approach for detecting and monitoring ocean fronts from Advanced Very High Resolution Radiometer (AVHRR) SST satellite images that builds on a previous “front following” algorithm. Weighted local likelihood is used to provide a smooth, nonparametric description of spatial variations in the position, mean temperature, width, and temperature change of an individual front within an image. Weightings are provided by a Gaussian kernel function whose width is automatically determined by likelihood cross-validation. The statistical model fitting approach allows estimation of the uncertainty of each parameter to be quantified, a capability not possessed by other techniques. The algorithm is shown to be robust to noise and missing data in an image, problems that hamper many of the existing front-detection schemes. The approach is general and could be used with other remotely sensed datasets, model output, or data assimilation products.
Information Needs of Parents of Children With Attention-Deficit/ Hyperactivity Disorder
Authors: Sciberras Emma , Iyer Shobha , Efron Daryl , Green Julie
Published: January 2010

Objective. To determine the information needs of parents of children with attention-deficit/hyperactivity disorder (ADHD). Method. A cross-sectional survey of parents recruited from pediatric hospital clinics, support groups, and newspaper advertisements in Victoria, Australia, was undertaken. Parents completed a questionnaire covering information sources accessed, the quality of this information, the information content they considered important and their preferred information modes. Results. Survey data were collected from 99 parents. Parents most frequently accessed information from pediatricians (89%), books (78%), general practitioners (65%), and schools (61%). Pediatricians were rated highest as a useful, trusted, easy-to-understand, and up-to-date information source. Parents placed most importance on causes and symptoms at the time of diagnosis. Parents preferred to receive verbal information from a professional (69%). Conclusion. Information provision for parents of children with ADHD is a continuous process. Although they access a range of sources and modes, parents prefer verbal information delivery.
Age-Specific Prevalence of Outdoor and Indoor Aeroallergen Sensitization in Boston
Authors: Sheehan William J. , Rangsithienchai Pitud A. , Baxi Sachin N. , Gardynski Andrea , Bharmanee Apinya , Israel Elliot , Phipatanakul Wanda
Published: January 2010

Questions exist regarding the appropriate age for referral of an atopic child to an allergist for environmental skin prick testing. This study evaluates age-specific prevalence of sensitization to aeroallergens from infancy through adolescence. A total of 1394 patients were skin tested, with 57.2% being sensitized to at least 1 aeroallergen. In children younger than 2, the authors found that 26.5% were sensitized, including to dogs (15.5%) and cats (9.2%). Additionally, tree sensitization was demonstrated in the youngest age group (7.8% at 0-2 years; 17.1% at 2-4 years), including in 3 infants less than 1 year old. Sensitization rates to dust mites and trees were the highest in all ages above 4 years, with a peak tree sensitization of 56.4% at 10 to 12 years and a peak dust mite sensitization of 56.8% in the >12 group. Overall, the authors observed increasing sensitization rates throughout childhood for indoor and outdoor aeroallergens ( P < .001). Aeroallergen sensitization begins at a young age and increases during childhood.
Parents’ Roles in Mediating and Buffering the Implementation of an Urban School Reform
Authors: Martinez-Cosio Maria
Published: January 2010

This article presents an analysis of a Latino parent group and an African American parent group in California who struggled to engage with a contentious urban school reform. Using Bourdieu’s cultural capital framework, the study focuses on the institutional responses to parent involvement, and the inequality in access that occurs as capital from different parent groups is validated or dismissed. Findings suggest that researchers also focus on school district responses to parents’ efforts at engagement and help highlight institutional obstacles.
Static Analysis of Cylindrical Sandwich Panels with a Flexible Core and Laminated Composite Face Sheets
Authors: Afshin Mehdi , Sadighi Mojtaba , Shakeri Mahmood
Published: January 2010

In this study, static response of cylindrical sandwich panels with flexible core based on the high-order theory (HOT) of sandwich structures is investigated. A layerwise formulation is developed to study the applicability of HOT. The face sheets are considered as composite laminates with cross-ply layup that follow first-order shear deformation assumption and the core is considered as a linear elastic medium with out-of-plane stresses only. The field equations along with the boundary conditions are derived by means of the principle of minimum potential energy. A closed-form solution is developed for simply supported boundary conditions and a comparison is made with results from the commercial finite element software ANSYS to verify high-order and layerwise solution results. Finally, influence of parameters including the core to face sheets stiffness ratio and the core to face sheets thickness ratio on the applicability of HOT is investigated. Results demonstrate a good agreement between high-order and layerwise results for the small thickness ratio of the core to the face sheet and low stiffness cores.