bluuebunny/crossref_metadata_2025 huggingface dataset:
Explanation component of software system
Authors: Wooley Bruce A.
Published: January 2009

Explanation is an important feature that needs to be integrated into software products. Early software that filled the horizontal software market (such as word processors) contained help systems. More specialized systems, known as expert systems, were developed to produce solutions that required specific domain knowledge of the problem being solved. The expert systems initially produced results that were consistent with the results produced by experts, but the expert systems only mimicked the rules the experts outlined. The decisions provided by expert systems include no justification, thus causing users to doubt the results reported by the system. If the user was dealing with a human expert, he could ask for a line of reasoning used to draw the conclusion. The line of reasoning provided by the human expert could then be inspected for discrepancies by another expert or verified in some other manner. Software systems need better explanations of how to use them and how they produce results. This will allow the users to take advantage of the numerous features being provided and increase their trust in the software product.
Environmental Effects on Spatial and Temporal Patterns of Leaf and Root Growth
Authors: Walter Achim , Silk Wendy K. , Schurr Ulrich
Published: January 2009

Leaves and roots live in dramatically different habitats, but are parts of the same organism. Automated image processing of time-lapse records of these organs has led to understanding of spatial and temporal patterns of growth on time scales from minutes to weeks. Growth zones in roots and leaves show distinct patterns during a diel cycle (24 h period). In dicot leaves under nonstressful conditions these patterns are characterized by endogenous rhythms, sometimes superimposed upon morphogenesis driven by environmental variation. In roots and monocot leaves the growth patterns depend more strongly on environmental fluctuations. Because the impact of spatial variations and temporal fluctuations of above- and belowground environmental parameters must be processed by the plant body as an entire system whose individual modules interact on different levels, growth reactions of individual modules are often highly nonlinear. A mechanistic understanding of plant resource use efficiency and performance in a dynamically fluctuating environment therefore requires an accurate analysis of leaf and root growth patterns in conjunction with knowledge of major intraplant communication systems and metabolic pathways.
Cholesterol 24-Hydroxylase: An Enzyme of Cholesterol Turnover in the Brain
Authors: Russell David W. , Halford Rebekkah W. , Ramirez Denise M.O. , Shah Rahul , Kotti Tiina
Published: January 2009

Cholesterol 24-hydroxylase is a highly conserved cytochrome P450 that is responsible for the majority of cholesterol turnover in the vertebrate central nervous system. The enzyme is expressed in neurons, including hippocampal and cortical neurons that are important for learning and memory formation. Disruption of the cholesterol 24-hydroxylase gene in the mouse reduces both cholesterol turnover and synthesis in the brain but does not alter steady-state levels of cholesterol in the tissue. The decline in synthesis reduces the flow of metabolites through the cholesterol biosynthetic pathway, of which one, geranylgeraniol diphosphate, is required for learning in the whole animal and for synaptic plasticity in vitro. This review focuses on how the link between cholesterol metabolism and higher-order brain function was experimentally established.
Immunomodulation of Allergic Disease
Authors: Broide David H.
Published: January 2009

This review focuses on sublingual immunotherapy (SLIT), toll-like receptor-9 (TLR-9) vaccines using cytosine phosphorothioate guanosine (CpG)–allergen conjugates, and anti-IL-5 as novel immunomodulating therapies in allergy. At present, all three approaches are investigational in the United States and require further study to determine their safety and effectiveness. SLIT provides a novel oral route of administering an allergen to induce tolerance to inhaled allergens. Studies of SLIT in allergic rhinitis demonstrate that it reduces symptoms and medication use and is associated with a low incidence of systemic allergic reactions. Initial phase II studies with TLR-9 vaccines conjugated to a ragweed allergen demonstrate that they reduce symptoms of allergic rhinitis during the ragweed season. Anti-IL-5 is effective as a corticosteroid-sparing agent in the hypereosinophilic syndrome. It has not shown benefit in moderate asthmatics with persistent symptoms but may reduce aspects of airway remodeling in asthma.
A synthetic farnesoid X receptor (FXR) agonist promotes cholesterol lowering in models of dyslipidemia
Authors: Evans Mark J. , Mahaney Paige E. , Borges-Marcucci Lisa , Lai KehDih , Wang Shuguang , Krueger Julie A. , Gardell Stephen J. , Huard Christine , Martinez Robert , Vlasuk George P. , Harnish Douglas C.
Published: January 2009

The nuclear hormone receptor farnesoid X receptor (FXR) plays a critical role in the regulation of bile acid, triglyceride (TG), and cholesterol homeostasis. WAY-362450 (FXR-450/XL335) is a potent synthetic FXR agonist as characterized in luciferase reporter assays and in mediating FXR target gene regulation in primary human and immortalized mouse hepatocytes. In vivo, WAY-362450 dose dependently decreased serum TG levels after 7 days of oral dosing in western diet-fed low-density lipoprotein receptor−/− mice and in the diabetic mouse strains KK-Ay and db/db comparable to that achieved with the peroxisome proliferator activated receptor-α agonist, fenofibrate. WAY-362450 treatment also reduced serum cholesterol levels via reductions in LDLc, VLDLc, and HDLc lipoprotein fractions that were not accompanied by hepatic cholesterol accumulation. This cholesterol lowering was dependent on FXR as demonstrated in a hypothyroid-induced hypercholesterolemia setting in FXR−/− mice. In fructose-fed models, WAY-362450 also decreased TG and VLDLc levels in rats and hamsters but significantly increased HDLc levels in rats while reducing HDLc levels in hamsters. The differential effect of WAY-362450 on HDLc is likely due to a murine-specific induction of endothelial lipase and scavenger receptor-BI that does not occur in rats. These studies demonstrate a consistent ability of WAY-362450 to lower both serum TG and cholesterol levels and suggest that synthetic FXR agonists may have clinical utility in the treatment of mixed dyslipidemia.
Creation of a standardized geometry of the human nasal cavity
Authors: Liu Y. , Johnson M. R. , Matida E. A. , Kherani S. , Marsan J.
Published: January 2009

A novel, standardized geometry of the human nasal cavity was created by aligning and processing 30 sets of computed tomography (CT) scans of nasal airways of healthy subjects. Digital three-dimensional (3-D) geometries of the 60 single human nasal cavities (30 right and 30 mirrored left cavities) were generated from the CT scans and measurements of physical parameters of each single nasal cavity were performed. A methodology was developed to scale, orient, and align the nasal geometries, after which 2-D digital coronal cross-sectional slices were generated. With the use of an innovative image processing algorithm, median cross-sectional geometries were created to match median physical parameters while retaining the unique geometric features of the human nasal cavity. From these idealized 2-D images, an original 3-D standardized median human nasal cavity was created. This new standardized geometry was compared against the original geometries of all subjects as well as limited existing data from the literature. The new model has potential for use as a geometric standard in future experimental and numerical studies of deposition of inhaled aerosols, as well as for use as a reference during diagnosis of unhealthy patients. The specific procedure developed could also be applied to build standard nasal geometries for different identifiable groups within the larger population.
Sensitization of capsaicin-sensitive lung vagal afferents by anandamide in rats: role of transient receptor potential vanilloid 1 receptors
Authors: Lin You Shuei , Lin Ruei-Lung , Bien Mauo-Ying , Ho Ching-Yin , Kou Yu Ru
Published: January 2009

Anandamide (AEA), an arachidonic acid derivative produced during inflammatory conditions, is an endogenous agonist of both transient receptor potential vanilloid 1 (TRPV1) receptors and cannabinoid CB1 receptors. Sensitization of capsaicin-sensitive lung vagal afferent (CSLVA) fibers by chemical mediators is important in the pathogenesis of hyperreactive airway diseases. We investigated the effect of the intravenous infusion of AEA (2 mg·kg−1·ml−1, 0.5 ml/min for 2 min) on the sensitivity of CSLVA fibers to chemical and mechanical stimulation in anesthetized rats. In artificially ventilated rats, AEA infusion only mildly elevated the baseline activity of CSLVA fibers. However, CSLVA fiber responses to right atrial injection of capsaicin, AEA, or adenosine and to lung inflation (tracheal pressure = 30 cmH2O) were all markedly potentiated during AEA infusion, which reverted 20 min after termination of the infusion. The potentiating effect on the sensitivity of CSLVA fibers to adenosine injection or lung inflation was completely blocked by pretreatment with capsazepine (a TRPV1 receptor antagonist) but was unaffected by pretreatment with AM281 (a CB1 receptor antagonist). In spontaneously breathing rats, right atrial injection of adenosine evoked an apneic response that is presumably mediated through CSLVA fibers. Similarly, the adenosine-evoked apneic response was potentiated during AEA infusion, and this potentiating effect was also completely prevented by pretreatment with capsazepine. These results suggest that AEA infusion at the dose tested produces a mild activation of TRPV1 receptors and this nonspecifically increases CSLVA fiber sensitivity to chemical and mechanical stimulation.
Triglycerides and Alanine Aminotransferase as Screening Markers for Suspected Fatty Liver Disease in Obese Children and Adolescents
Authors: Oliveira Ana M. , Oliveira Nelson , Reis Jussara C. , Santos Marcos V. , Silva Agnaluce M. , Adan Luis
Published: January 2009

Background/Aims: Metabolic syndrome (MS) and fatty liver disease (FLD) are on the rise. The association between these conditions in Brazilian youth is analyzed. Methods: 354 subjects (11.2 ± 3.1 years) were evaluated. FLD was suspected by ultrasound and computed tomography; weight and MS by BMI z-score and NCEP-ATPIII respectively. Results: Subjects were classified as: group 1 with suspected FLD and group 2 without and group 2 as ‘a’ (overweight/obese) and ‘b’ (normal weight). Comparing group 1 with 2a and 2b, differences in age (p = 0.016; p = 0.075), triglycerides (TG) (p = 0.021; p = 0.002), insulin (p = 0.652; p = 0.015) and homeostasis model assessment method of IR (HOMA-IR) (p = 0.737; p = 0.003) were found. Group 2a was divided into low/high alanine aminotransferase (ALT). A decrease in waist circumference and TG was found going from those with suspicion of FLD to obese with high and low ALT. Insulin and HOMA-IR in group 1 and high ALT were similar. Gender (OR 6.6; CI 1.9–22.5; p = 0.025), age (OR 1.3; CI 1.1–1.6; p = 0.006), TG (OR 10.4; CI 3.1–34.4; p = 0.005) were associated with suspected FLD. For every 10 U/l increase in ALT, there was a 4-fold greater chance of probable FLD (OR 4.01; CI 2.06–9.40; p < 0.001). Conclusion: Measurements of ALT and TG should be considered as screening for suspected FLD in overweight/obese youth.
Autosomal Dominant Neurohypophyseal Diabetes Insipidus in Two Families
Authors: Hedrich C.M. , Zachurzok-Buczynska A. , Gawlik A. , Russ S. , Hahn G. , Koehler K. , Malecka-Tendera E. , Huebner A.
Published: January 2009

Background: Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease with symptoms of polydipsia, polyuria and dehydration caused by arginine vasopressin deficiency. Disease onset is within infancy or adolescence. A variety of disease-causing mutations of the arginine vasopressin neurophysin II gene (AVP) on chromosome 20p13 have been described. Methods: Two Polish families with adFNDI were screened for mutations. Processing of wild-type (WT) and mutant AVP was monitored using immunocytochemical methods in stably transfected Neuro2A cells. AVP secretion into the cell culture supernatant was investigated with an enzyme immunoassay. Results: In the first family a heterozygous p.G96D mutation was identified. Some patients additionally carried a novel heterozygous mutation p.A159T. The second family presented with a heterozygous mutation p.C98G. Confocal laser microscopy unveiled accumulation of p.G96D and p.C98G prohormones in the cellular bodies, whereas WT and p.A159T prohormones and/or processed products were located in the tips of cellular processes. Reduced levels of AVP in supernatant culture medium of p.G96D and p.C98G transfected cells in comparison to p.A159T and WT cells were found. Conclusions: We conclude that the p.G96D and p.C98G mutations cause adFNDI in the two reported families. The sequence variant p.A159T does not seem to have disease-causing effects.
X-Linked Adrenal Hypoplasia Congenita Caused by a Novel Intronic Mutation of the DAX-1 Gene
Authors: Goto Masahiro , Katsumata Noriyuki
Published: January 2009

Objective: X-linked adrenal hypoplasia congenita (AHC) associated with hypogonadotropic hypogonadism (HHG) is caused by mutations of the DAX-1 gene. A novel intronic mutation of the gene and the results of in vitro expression analysis are reported. Patient and Methods: The patient is a 13-year-old boy who presented with severe dehydration and salt loss in the neonatal period, when he lacked cutaneous pigmentation and elevation of plasma ACTH level. He had been diagnosed and treated as adrenal hypoplasia. The DAX-1 gene was analyzed by direct DNA sequencing in the patient and his parents. In vitro expression analysis was applied to confirm the consequent missplicing of mRNA caused by the mutation. Results: The substitution of guanine for cytosine at the splice donor site (IVS1 + 1G>C) was observed in our patient and his mother. Expression analysis suggested that this mutation may hinder splicing of the adjacent intron and cause alternative activation of three cryptic splice donor sites within exon 1 leading to the aberrant splicing of mRNA and production of truncated proteins. Conclusion: To our knowledge, this is the first case report of AHC associated with HHG caused by an intronic mutation of the DAX-1 gene. The clinical course of our patient may suggest that the onset of mineralocorticoid deficiency can precede that of glucocorticoid deficiency in some patients with AHC, and thus appear to suffer from aldosterone synthase deficiency at the onset of the disease.
Aerodynamics of the Pseudo-Glottis
Authors: Kotby M.N. , Hegazi M.A. , Kamal I. , Gamal el Dien N. , Nassar J.
Published: January 2009

Objective: The aim of this work is to study the hitherto unclear aerodynamic parameters of the pseudo-glottis following total laryngectomy. These parameters include airflow rate, sub-pseudo-glottic pressure (SubPsG), efficiency and resistance, as well as sound pressure level (SPL). Patients and Methods: Eighteen male patients who have undergone total laryngectomy, with an age range from 54 to 72 years, were investigated in this study. All tested patients were fluent esophageal ‘voice’ speakers utilizing tracheo-esophageal prosthesis. The airflow rate, SubPsG and SPL were measured. Results: The results showed that the mean value of the airflow rate was 53 ml/s, the SubPsG pressure was 13 cm H2O, while the SPL was 66 dB. The normative data obtained from the true glottis in healthy age-matched subjects are 89 ml/s, 7.9 cm H2O and 70 dB, respectively. Other aerodynamic indices were calculated and compared to the data obtained from the true glottis. Conclusion: Such a comparison of the pseudo-glottic aerodynamic data to the data of the true glottis gives an insight into the mechanism of action of the pseudo-glottis. The data obtained suggests possible clinical applications in pseudo-voice training.
Craniorachischisis Totalis: A Case Report and Review of the Literature
Authors: Coskun A. , Kiran G. , Ozdemir O.
Published: January 2009

Objective: To discuss a fetus with craniorachischisis diagnosed antenatally and to review the literature. Method: Case report. Results: Craniorachischisis was detected on ultrasound scan in a fetus at gestational week 13. Pregnancy was terminated and diagnosis was verified postnatally. Conclusion: Craniorachischisis is a rare and severe form of neural tube defects (NTDs). The majority of currently known cases of mouse craniorachischisis have been found to result from disturbance of a single molecular signaling cascade, called planar cell polarity pathway (PCP). The mutant genes that have been causative in disturbance of PCP in mouse models have been examined in human malformations but none of them have so far been implicated in human craniorachischisis. To date, no other genes except the gene encoding 5,10-methylenetetrahydrofolate reductase have been specifically implicated in predisposition to NTDs. We suggest that other PCP genes should be considered as candidates for a role in the etiology of human NTDs. Further investigations are therefore necessary.
Percutaneous Laser Ablation of Sacrococcygeal Teratoma in a Hydropic Fetus with Severe Heart Failure – Too Late for a Surgical Procedure?
Authors: Ruano Rodrigo , Duarte Sergio , Zugaib Marcelo
Published: January 2009

Sacrococcygeal teratoma (SCT) is the commonest solid fetal tumor. Perinatal prognosis is usually favorable, but sometimes it can be complicated by fetal hydrops being responsible for high risk of mortality. Fetal therapy in such cases has so far not been established. We report a case with a giant solid SCT associated with fetal hydrops and severe heart failure. 2D- and 3D-Doppler ultrasonography revealed great vessels originated from the medial sacral artery. Percutaneous laser ablation of these vessels was performed at 24 weeks of gestation. During the procedure, severe anemia was also diagnosed (hemoglobin 4.3 g/dl). Two days later, the fetus died and pathological examination revealed local tumor necrosis and blood hemorrhage inside the mass. We suggest that in such cases, fetal surgery may not be enough, being too late, and perhaps fetal clinical therapy for anemia and heart failure could be the best option at a gestational age of less than 28 weeks.
Association between Sweetened Beverage Consumption and Body Mass Index, Proportion of Body Fat and Body Fat Distribution in Mexican Adolescents
Authors: Denova-Gutiérrez E. , Jiménez-Aguilar A. , Halley-Castillo E. , Huitrón-Bravo G. , Talavera J.O. , Pineda-Pérez D. , Díaz-Montiel J.C. , Salmerón J.
Published: January 2009

Background/Aims: It was the aim of this study to evaluate the relationships between sweetened beverage (SB) consumption and the following indicators of overweight/fatness among Mexican adolescents: body mass index, body composition and body fat distribution. Methods: We performed a cross-sectional analysis of data from adolescents participating in the baseline assessment of the Health Workers Cohort Study. Information on sociodemographic conditions, sexual maturation, dietary patterns and physical activity was collected via self-administered questionnaires. SB consumption was evaluated through a validated semiquantitative food frequency questionnaire. Anthropometric measures were assessed with standardized procedures. The associations of interest were evaluated by means of multivariate regression and logistic regression models. Results: A total of 1,055 adolescents, 10–19 years old (mean age 14.5 ± 2.5 years), were evaluated. The overweight/obesity prevalence was 31.6% among girls and 31.9% among boys. We found that for each additional SB serving consumed daily, the subject’s body mass index increased by on average 0.33 (p < 0.001). Subjects consuming 3 daily servings of SB face a 2.1 times greater risk of proportionally excess body fat than those who consume less than 1 SB a day. Conclusions: Our data support the hypothesis that the consumption of SB increases the risk of overweight and/or obesity and encourages excess body fat and central obesity in Mexican adolescents.
Ethanol Consumption Does Not Promote Weight Gain in Female Mice
Authors: Smith Rebekah R. , Hong Jina , Harvey Alison E. , Lewis Tamara , Diaz Daniel , Núñez Nomelí P.
Published: January 2009

Background: The prevalence of obese adult women has increased dramatically in the United States. Individuals consuming alcoholic beverages may obtain as much as 6–10% of their calories from ethanol; consequently, ethanol may contribute to a positive energy balance and weight gain in women consuming ethanol. The objective of these studies is to determine if ethanol consumption affects weight gain or body fat levels in female mice. Methods: In order to determine the effects of ethanol consumption on weight gain, female mice were given either water or 20% w/v ethanol in the drinking water; mice were then placed on 1 of 3 diets for 20 weeks: (1) 30% calorie-restricted diet, (2) low-fat diet or (3) high-fat diet. Mice were scanned using a GE Lunar Piximus Densitometer to determine body fat, lean body mass and bone mineral density. Results: Mice consuming the high-fat diet had the highest body weight. Moreover, ovariectomy exacerbated the effects of the high-fat diet. That is, ovariectomized female mice consuming the high-fat diet gained a higher amount of body weight and adipose tissue than nonovariectomized mice consuming the high-fat diet. Ethanol-consuming mice did not have a higher susceptibility to gaining body weight or body fat, even though they tended to have higher caloric intake than water-consuming mice. Conclusions: In female mice that consumed a high-fat diet, chronic ethanol consumption did not increase susceptibility to gaining weight or becoming obese.
Human Carotid Plaque Calcification and Vulnerability
Authors: Wahlgren Carl-Magnus , Zheng Wei , Shaalan Wael , Tang Jun , Bassiouny Hisham S.
Published: January 2009

Background: Inflammation is a key mechanism in human atherosclerotic plaque vulnerability and disruption. The objective was to determine the differential gene expression of pro- and anti-inflammatory factors in the fibrous cap and shoulder region of noncalcified and calcified carotid endarterectomy plaques. Methods: Thirty carotid endarterectomy plaques were classified as type Va (noncalcified, n = 15) and type Vb (calcified, n = 15) in accordance with the American Heart Association consensus. Using laser capture microdissection, fibrous cap and shoulder regions were excisedfrom frozen sections. Gene expression of pro- [interleukin 1 (IL-1), IL-8 and monocyte chemoattractant protein 1 (MCP-1)] and anti-inflammatory (IL-10) factors, and bone formation (bone morphogenetic protein 6 and osteocalcin) mediators were quantitated by real-time PCR. Protein levels were determined using Western blotting. Results: Mean percent carotid stenosis and calcification area were 79 and 5% in Va-plaques (40% symptomatic) and 77 and 42% in Vb-plaques (20% symptomatic). Macrophages infiltrating the region of the fibrous cap and the shoulder were more numerous in non-calcified plaques compared with calcified plaques (p < 0.01]. mRNA expression of MCP-1 and IL-8, and protein levels of IL-8 were also greater in Va plaques compared to Vb plaques (p < 0.05). Protein levels and mRNA expression of osteocalcin were greater in Vb compared to Va plaques (p < 0.05). Conclusions: Fibrous cap inflammation is more likely to occur in noncalcified than in calcified plaques. These findings suggest that carotid atherosclerotic plaque calcification is a structural marker of plaque stability.
Audiometric Characteristics of USH2a Patients
Authors: Leijendeckers Joop M. , Pennings Ronald J.E. , Snik Ad F.M. , Bosman Arjan J. , Cremers Cor W.R.J.
Published: January 2009

Temporal processing, frequency discrimination and frequency resolution, three basic mechanisms involved in speech perception, were studied in 11 USH2a patients from 10 Dutch families. Measurements included loudness scaling, gap detection, determination of auditory filter shapes and difference limen for frequency. The results were compared to values obtained from listeners with normal hearing, DFNA8/12 patients, DFNA13 patients and unselected patients with presbyacusis. Overall, the results for USH2a were most similar to those obtained in patients with sensorineural hearing loss caused by hair cell defects. To our knowledge, this is the first study that presents results on audiometric measurements combined with psychophysical measurements in a group of USH2a patients.
Broca’s Aphasiacs
Authors: Pearce J.M.S.
Published: January 2009

After Gall, Bouillaud and Auburtin had localized the function of language to the frontal lobes in the early 19th century, Paul Broca’s famous patient, M. Leborgne (known as ‘Tan’), was described to the Anthropological Society of Paris and his case was published in the Bulletin de la Société Anatomique, in 1861. Broca relied on the uncut brain for his clinicopathological inferences. A few months later, his second case, M. Lelong, yielded similar pathological details and confirmed Broca’s localization of language. The subsequent controversies with Dax and Pierre Marie are summarized. More recent imaging of the brains of Lelong and Leborgne has partly vindicated Broca’s controversial conclusions. Most papers on Broca’s work contain only brief, derivative references to his 1861 paper; the actual contents, translated into English, are reproduced here.
Meta-Analysis of Enteral Nutrition versus Total Parenteral Nutrition in Patients with Severe Acute Pancreatitis
Authors: Cao Yunfei , Xu Yinglong , Lu Tingna , Gao Feng , Mo Zengnan
Published: January 2009

Objective: To compare the safety of enteral nutrition and total parenteral nutrition in nutrition support of patients with severe acute pancreatitis. Methods: Data sources: Medline, Embase, and manual search. Study selection: 295 articles were screened for randomized controlled studies (RCTs) that compared enteral nutrition with total parenteral nutrition in patients with severe acute pancreatitis. Finally, six RCTs were identified and included in the meta-analysis. Data extraction: six RCTs with 224 participants were analyzed. The main outcome were infections, artificial nutrition-related complications, pancreatitis-related complications, non-pancreatitis-related complications, organ failure and mortality. The meta-analysis was performed with the fixed effects model or random effects model. Results: Compared with total parenteral nutrition, enteral nutrition was associated with a significantly lower risk of infections [odds ratio (OR) 0.236; 95% confidence interval (95% CI) 0.120–0.464, p < 0.001], pancreatitis-related complications (0.456; 0.234–0.888, p = 0.021), organ failure (0.334; 0.167–0.670, p = 0.002), multiple organ dysfunction syndrome (0.306; 0.128–0.736, p = 0.008), and mortality (0.251; 0.095–0.666, p = 0.005). There were no significant differences in artificial nutrition-related complications (0.642; 0.354–1.162, p = 0.143), and non-pancreatitis-related complications (0.716; 0.325–1.576, p = 0.406) between the two groups. Conclusions: Enteral nutrition appears safer than total parenteral nutrition in nutrition support of patients with severe acute pancreatitis.
Effects of α-Amylase and Its Inhibitors on Acid Production from Cooked Starch by Oral Streptococci
Authors: Aizawa S. , Miyasawa-Hori H. , Nakajo K. , Washio J. , Mayanagi H. , Fukumoto S. , Takahashi N.
Published: January 2009

This study evaluated acid production from cooked starch by Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguinis and Streptococcus mitis, and the effects of α-amylase inhibitors (maltotriitol and acarbose) and xylitol on acid production. Streptococcal cell suspensions were anaerobically incubated with various carbohydrates that included cooked potato starch in the presence or absence of α-amylase. Subsequently, the fall in pH and the acid production rate at pH 7.0 were measured. In addition, the effects of adding α-amylase inhibitors and xylitol to the reaction mixture were evaluated. In the absence of α-amylase, both the fall in pH and the acid production rate from cooked starch were small. On the other hand, in the presence of α-amylase, the pH fell to 3.9–4.4 and the acid production rate was 0.61–0.92 μmol per optical density unit per min. These values were comparable to those for maltose. When using cooked starch, the fall in pH by S. sanguinis and S. mitis was similar to that by S. mutans and S. sobrinus. For all streptococci, α-amylase inhibitors caused a decrease in acid production from cooked starch, although xylitol only decreased acid production by S. mutans and S. sobrinus. These results suggest that cooked starch is potentially acidogenic in the presence of α-amylase, which occurs in the oral cavity. In terms of the acidogenic potential of cooked starch, S. sanguinis and S. mitis were comparable to S. mutans and S. sobrinus. α-Amylase inhibitors and xylitol might moderate this activity.
Relationship between Drug Treatment Engagement and Criminal Thinking Style among Drug-Using Offenders
Authors: Best David , Day Ed , Campbell Angela , Flynn Patrick M. , Simpson D. Dwayne
Published: January 2009

There has been considerable debate about the effectiveness of drug treatment in reducing offending and drug use, with limited support for the effectiveness of the UK Drug Intervention Programme to reduce offending through diversion into treatment. The current paper examines drug users diverted into treatment in one UK city to assess their treatment engagement and criminal thinking styles. There is an association between higher criminal thinking and both poorer engagement in treatment and worse client functioning. The key implication is that to address offending-prone behaviour as a determinant of ongoing drug use, it is essential that criminal thinking styles are addressed.
Decision Making of Heavy Cannabis Users on the Iowa Gambling Task: Stronger Association with THC of Hair Analysis than with Personality Traits of the Tridimensional Personality Questionnaire
Authors: Hermann Derik , Leménager Tagrid , Gelbke Jan , Welzel Helga , Skopp Gisela , Mann Karl
Published: January 2009

Background: It is unclear whether impairment in decision making, measured by the Iowa Gambling Task (IGT), in addiction is substance-induced or the consequence of personality structure. Methods: Analysis of the IGT, the Tridimensional Personality Questionnaire (TPQ) and cannabinoids in hair and urine were performed in 13 cannabis users and matched controls. Results: Hair Δ9-tetrahydrocannabinol (THC) correlated negatively with the last subtrial (cards 80–100) of the IGT (R = –0.67). In all participants (n = 26) the TPQ dimension, harm avoidance, correlated negatively with the total IGT score (R = –0.46). The last IGT-subtrial correlated with adventure seeking (R = 0.43), harm avoidance (R = –0.39) and reward dependence (R = –0.44). The last subtrial gives information on whether a participant has learned the IGT strategy. Multiple regression confirmed the impact of THC on the last subtrial, whereas TPQ personality traits did not additionally explain variance. Conclusions: Former indications of the IGT performance depending on the amount of cannabis consumed were replicated with an objective measurement of chronic cannabis consumption (hair THC). Multiple regression analysis argues for a stronger impact of chronic THC consumption than personality traits, but does not provide a causal relationship. Other factors (e.g. genetic) may also play a role.
Early Reduction of QT Dispersion after Primary Percutaneous Intervention in ST-Segment Elevation Acute Myocardial Infarction
Authors: Jiménez-Candil Javier , Hernández Hernández Jesús , Agüero Víctor León , Martín Ana , Martín Francisco , Moríñigo José Luis , Martín-Luengo Cándido
Published: January 2009

Objectives: To determine, in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI), the mechanisms and clinical implications of the acute changes in QT dispersion (QTd). Methods: In this prospective study we included 216 patients admitted with a STEMI of <12 h of evolution. All were treated with PPCI. QTd was measured prior to PPCI and within 1 h after. Results: The ratio of QTd reduction after PPCI (QTd-R) – defined as [(QTd before PPCI – QTd after PPCI)/QTd before PPCI] ×100 – was significantly correlated with the percentage of ST-segment elevation resolution (ST-R; p < 0.001). To determine the significance of the different values of QTd-R, we further subdivided our population into 3 groups according to the tertiles of QTd-R (<10, 11–49, ≥50%). Patients with longer QTd-R had higher percentages of ST-R: 32 ± 43 for QTd-R <10% vs. 60 ± 21 for 11–49% vs. 71 ± 12 for ≥50% (p < 0.05). By logistic regression, patients with QTd-R ≥50% had a reduction of 75% in the adjusted frequency of death or severe heart failure during hospitalization (95% CI 13–73%, p = 0.03). Conclusion: QTd-R after PPCI occurs early, is closely related to the restoration of reperfusion at the microvascular level and provides additional prognostic information.
Abnormalities in Stratum Corneum Function in Patients Recovered from Leprosy
Authors: Song S.-P. , Lv C.-Z. , Feingold K.R. , Hou Q.-N. , Li Z.-Y. , Guo C.-Y. , Elias P.M. , Man M.Q.
Published: January 2009

Background and Objectives: Leprosy involves both the skin and peripheral nervous system. Leprosy patients display an increased incidence of xerosis and altered sensory thresholds, which persist in previously active skin sites. We assessed here whether alterations in stratum corneum (SC) function persist in cured leprosy, and the relationship of epidermal functional abnormalities to each clinical subtype of leprosy. Methods: A total of 43 cured leprosy subjects and 29 normal control subjects were enrolled in this study. Basal skin surface pH, SC hydration, permeability barrier function as well as barrier recovery rates were measured over previously involved skin sites with a skin physiology monitor. One-way ANOVA and two-tailed Student’s t test were used to determine the significance between 2 groups and 3 or more groups, respectively. Results: Competent barrier function was observed in all subtypes of cured leprosy subjects. All cured leprosy subjects except those with the borderline tuberculoid type exhibited a significantly lower SC hydration in comparison with normal subjects. Skin surface pH was significantly elevated in all cured leprosy subjects in comparison with normal subjects. Conclusions: A varied spectrum of alterations in SC function remains in all subjects who have recovered from leprosy, but the spectrum of SC functional abnormalities varies with disease subtype.
Vero Cells as a Model to Study the Effects of Adenoviral Gene Delivery Vectors on the RNAi System in Context of Viral Infection
Authors: Matskevich Alexey A. , Jung Jiun-Shan , Schümann Michael , Cascallo Manel , Moelling Karin
Published: January 2009

Technology based on RNA interference (RNAi) is a promising source for new antiviral therapies. Although the application of RNAi has been studied extensively, significant problems with using RNAi remain. Very few studies have specifically assessed model systems for testing the effects of viruses or gene delivery vectors on the RNAi system. Since viruses have developed efficient strategies to circumvent the interferon (IFN) response, an IFN-deficient model system should be considered. Here we show that in Vero cells, which lack IFN-α and IFN-β genes, knockdown of Dicer, a key RNAi component, led to accelerated death of cells infected with other evolutionary distinct viruses: influenza A virus, vesicular stomatitis virus and poliovirus. We also demonstrate that transduction of Vero cells with adenoviral vector with subsequent infection with influenza A virus also resulted in increased mortality of infected cells. These effects were much weaker in IFN-producing A549 and Hela cell lines. Thus, the Vero cell line could serve as an interesting model for studying the effects of gene delivery vectors on the RNAi system in the context of virus-related disorders.
The Roles of Toll-Like Receptors in Atherosclerosis
Authors: Erridge Clett
Published: January 2009

Atherosclerosis is a chronic inflammatory disease of the arteries that is characterised by the activation of endothelial cells, the recruitment of monocytes into the vessel wall and the differentiation of recruited macrophages into cholesterol-laden foam cells. Recent evidence from a variety of experimental approaches has indicated that Toll-like receptors (TLRs), which serve to initiate inflammatory signalling in response to the detection of molecules associated with microbial infection or tissue damage, play key roles in the development of atherosclerosis. This review summarises the recent evidence implicating TLR-dependent signalling in the activation of vascular cells during atherogenesis, and the mechanisms by which TLR-signalling may promote the dysregulation of macrophage cholesterol metabolism that is a prerequisite for the formation of foam cells and lesion progressionin vivo. Particular attention is paid to the recent studies aimed at identifying potential ligands of the TLRs that may be relevant to atherogenesis, and the diverse mechanisms by which vascular tissues may become exposed to ligands of the TLRs.
Glomerular Transcriptome Changes Associated with Lipopolysaccharide-Induced Proteinuria
Authors: Sun Ying , He Liqun , Takemoto Minoru , Patrakka Jaakko , Pikkarainen Timo , Genové Guillem , Norlin Jenny , Truvé Katarina , Tryggvason Karl , Betsholtz Christer
Published: January 2009

Background: Global gene expression patterns have recently been characterized in normal glomeruli, but gene expression changes that accompany glomerular disease remain poorly characterized. Method: Here, we mapped global glomerular gene expression profile changes occurring in conjunction with lipopolysaccharide (LPS)-induced proteinuria in mice. Results: We observed dramatic transcriptional reprogramming in glomeruli in response to LPS, representing some 20% of all genes and about 45% of the genes that are normally highly expressed in glomeruli. Bioinformatic analysis revealed significant changes in transcripts encoding proteins involved in the regulation of adherence junctions, actin cytoskeleton and survival in podocytes. In the LPS-treated mice, we observed dysregulation of genes expressed in glomerular endothelial and mesangial cells and in podocytes, there was also a significant decrease in podocyte number. Moreover, collagen α1, α2 (IV) and laminin 10 (laminin α5β1γ1), which are expressed in immature glomeruli, were upregulated in the glomeruli of LPS-treated mice, suggesting remodeling of the glomerular basement membrane and activation of mesangial cells. By superimposing the LPS-induced changes onto GlomNet, a protein-protein interaction network was predicted for podocyte proteins affected by LPS. Conclusions: The detected changes in glomerular gene expression and their involvement in protein interaction networks provide putative markers for early and transient glomerular injury and proteinuria.
Sex Differences in the Cannabinoid Modulation of Appetite, Body Temperature and Neurotransmission at POMC Synapses
Authors: Diaz Shanna , Farhang Borzoo , Hoien Joshua , Stahlman Megan , Adatia Nadira , Cox Jeremy M. , Wagner Edward J.
Published: January 2009

We sought to determine whether sex differences exist for the cannabinoid modulation of appetite, body temperature and neurotransmission at pro-opiomelanocortin (POMC) synapses. Gonadectomized male and female guinea pigs were outfitted to monitor core body temperature and injected with either the CB1 receptor agonist WIN 55,212-2 (1 mg/kg s.c.), antagonist AM251 (3 mg/kg s.c.) or vehicle (1 ml/kg s.c.) and evaluated for changes in six indices of feeding behavior under ad libitum conditions for 7 days. WIN 55,212-2 elicited an overt, sexually differentiated hyperphagia in which males displayed larger increases in hourly and daily intake, consumption/gram body weight, meal size and meal duration. The agonist also produced a more robust acute hypothermia in males than in females. In addition, males were more sensitive to the hypophagic effect of AM251, manifested by comparatively sizeable decreases in hourly intake, consumption/gram body weight, meal frequency and hyperthermia. To gain additional insight into the cellular mechanism underlying cannabinoid regulation of energy homeostasis, we performed whole-cell patch clamp recordings in hypothalamic slices prepared from gonadectomized male and female guinea pigs, and monitored miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) in arcuate (ARC) neurons. ARC neurons from females exhibited a higher basal mEPSC frequency. WIN 55,212-2 dose-dependently reduced mEPSC and mIPSC frequency; however, cells from males were far less sensitive to the CB1 receptor-mediated decrease in mIPSC frequency. These effects were observed in neurons subsequently identified as POMC neurons. These data reveal pronounced sex differences in how cannabinoids influence the hypothalamic control of homeostasis.
Daily Changes in GT1–7 Cell Sensitivity to GnRH Secretagogues That Trigger Ovulation
Authors: Zhao Sheng , Kriegsfeld Lance J.
Published: January 2009

Circadian rhythms in behavior and physiology are orchestrated by a master biological clock located in the suprachiasmatic nucleus (SCN). Circadian oscillations are a cellular property, with ‘clock’ genes and their protein products forming transcription-translation feedback loops that maintain 24-hour rhythmicity. Although the expression of clock genes is thought to be ubiquitous, the function of local, extra-SCN timing mechanisms remains elusive. We hypothesized that extra-SCN clock genes control local temporal sensitivity to upstream modulatory signals, allowing system-specific processes to be carried out during individual, optimal times of day. To test this possibility, we examined changes in the sensitivity of immortalized GnRH neurons, GT1–7 cells, to timed stimulation by two key neuropeptides thought to trigger ovulation on the afternoon of proestrus, kisspeptin and vasoactive intestinal polypeptide (VIP). We noted a prominent daily rhythm of clock gene expression in this cell line. GT1–7 cells also exhibited daily changes in cellular peptide expression and GnRH secretion in response to kisspeptin and VIP stimulation. These responses occurred without changes in GnRH transcription. These findings are consistent with the notion that GnRH cells are capable of intrinsic circadian cycles that may be fundamental for coordinating daily changes in sensitivity to signals impacting the reproductive axis.
AMP-Activated Protein Kinase Functionally Phosphorylates Endothelial Nitric Oxide Synthase Ser633
Authors: Chen Zhen , Peng I-Chen , Sun Wei , Su Mei-I , Hsu Pang-Hung , Fu Yi , Zhu Yi , DeFea Kathryn , Pan Songqin , Tsai Ming-Daw , Shyy John Y-J.
Published: January 2009

Endothelial nitric oxide synthase (eNOS) plays a central role in maintaining cardiovascular homeostasis by controlling NO bioavailability. The activity of eNOS in vascular endothelial cells (ECs) largely depends on posttranslational modifications, including phosphorylation. Because the activity of AMP-activated protein kinase (AMPK) in ECs can be increased by multiple cardiovascular events, we studied the phosphorylation of eNOS Ser633 by AMPK and examined its functional relevance in the mouse models. Shear stress, atorvastatin, and adiponectin all increased AMPK Thr172 and eNOS Ser633 phosphorylations, which were abolished if AMPK was pharmacologically inhibited or genetically ablated. The constitutively active form of AMPK or an AMPK agonist caused a sustained Ser633 phosphorylation. Expression of gain-/loss-of-function eNOS mutants revealed that Ser633 phosphorylation is important for NO production. The aorta of AMPKα2
−/−
mice showed attenuated atorvastatin-induced eNOS phosphorylation. Nano–liquid chromatography/tandem mass spectrometry (LC/MS/MS) confirmed that eNOS Ser633 was able to compete with Ser1177 or acetyl-coenzyme A carboxylase Ser79 for AMPKα phosphorylation. Nano-LC/MS/MS confirmed that eNOS purified from AICAR-treated ECs was phosphorylated at both Ser633 and Ser1177. Our results indicate that AMPK phosphorylation of eNOS Ser633 is a functional signaling event for NO bioavailability in ECs.
The Asymmetric Vascular Stent
Authors: Ionita Ciprian N. , Paciorek Ann M. , Dohatcu Andreea , Hoffmann Kenneth R. , Bednarek Daniel R. , Kolega John , Levy Elad I. , Hopkins L. Nelson , Rudin Stephen , Mocco J. Duffy
Published: January 2009

Background and Purpose—

Development of hemodynamic modifying devices to treat intracranial aneurysms is an active area of research. The asymmetrical vascular stent (AVS), a stent containing a low-porosity patch, is such device. We evaluate AVS efficacy in an in vivo intracranial aneurysm model.

Methods—

We created 24 elastase rabbit model aneurysms: 13 treated with the AVS, 5 treated with standard coronary stents, and 6 untreated controls. Four weeks after treatment, aneurysms underwent follow-up angiography, cone-beam micro-CT, histological evaluation, and selective electron microscopy scanning.

Results—

Four rabbits died early in the study: 3 during AVS treatment and 1 control (secondary to intraprocedural vessel injury and an unrelated tumor, respectively). AVS-treated aneurysms exhibited very weak or no aneurysm flow immediately after treatment and no flow in all aneurysms at follow-up. Standard stent-treated aneurysms showed flow both after treatment (5/5) and at follow-up (3/5). All control aneurysms remained patent during the study. Micro-CT scans showed: 9 of 9 scanned AVS aneurysms were occluded, 6 of 9 AVS were ideally placed, and 3 of 9 low-porosity region partially covered the aneurysm neck; standard stent-treated aneurysms were 1 of 5 occluded, 2 of 5 patent, and 2 of 5 partially patent. Histology results demonstrated: for AVS-treated aneurysms, advanced thrombus organization in the (9/9); for standard stent-treated aneurysms, (1/4) no thrombus, (2/4) partially thrombosed, and (1/4) fully thrombosed; for control aneurysms (4/4), no thrombus.

Conclusion—

The use of AVS shows promise as a viable new therapeutic in intracranial aneurysm treatment. These data encourage further investigation and provide substantial support to the AVS concept.
Genetic Variation in the Leukotriene Pathway and Carotid Intima-Media Thickness
Authors: Bevan Steve , Lorenz Matthias W , Sitzer Matthias , Markus Hugh S.
Published: January 2009

Background and Purpose—

The recent finding that genetic variation in the leukotriene biosynthesis pathway may confer an increased risk of ischemic stroke and atherosclerosis has implicated the leukotriene family as potential mediators of cardiovascular disease. Using a 2-stage replication design, we have examined whether polymorphisms in 8 genes related to this pathway are associated with early atherosclerosis and remodeling as measured by carotid artery intima-media thickness.

Methods—

We assessed 969 individuals from the Carotid Atherosclerosis Progression Study (CAPS), a community based study of normal subjects, for 39 variants in the leukotriene pathway. Significant associations and gene–environment interactions were found for 21 variants in the initial cohort and were examined in the next 1905 consecutive cases from the same CAPS population.

Results—

No replicable association between any individual polymorphism and carotid intima-media thickness itself was present after correction for multiple testing. A single gene–environment interaction was replicated between rs17222814 on bifurcation intima-media thickness and alcohol consumption exceeding 30 grams per day.

Conclusion—

The genetic variants we examined in the leukotriene biosynthesis pathway have little effect on early atherosclerosis and remodeling risk as determined by carotid intima-media thickness. Our study cannot exclude them as being risk factors for more advanced stages in the atherosclerotic process.