bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelin-1 and Endothelin Receptor Gene Variants and Their Association With Negative Outcomes Following Aneurysmal Subarachnoid Hemorrhage
Authors: Gallek Matthew , Alexander Sheila , Crago Elizabeth , Sherwood Paula , Horowitz Michael , Poloyac Samuel , Conley Yvette
Published: September 2012

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease that affects approximately 30,000 people a year in the United States. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CV) are common complications after aSAH. In addition, aSAH patients have a high risk of poor long-term outcomes. Endothelin-1 (ET-1), a potent vasoconstrictor, or its two types of receptors, ET receptor A (ETA ) and ET receptor B (ETB), may play a role in the pathogenesis of DCI and CV. Genetic variations within the ET-1, ETA, or ETB genes may also account for variance observed in the outcomes of aSAH patients. The purpose of this study was to describe the distribution of the Lys198Asn polymorphism, a known functional SNP in the ET-1 gene, and tagging SNPs of the ET-1, ETA, and ETB genes in individuals recovering from aSAH. This study also investigated the relationships among the ET polymorphisms, DCI, and global functional outcomes measured at 3 and 6 months after aSAH. Participants included individuals aged 18–75 years with a diagnosis of aSAH. There was a trend found between the variant allele of an ET-1 SNP (rs6912834) and angiographic vasospasm. There were also associations found between two ETB SNPs (rs9574124 and rs3027111) and poor outcomes as measured by the Glasgow Outcome scale at 3 months. These findings support the role of ET-1 and ETB in recovery following aSAH.
Hindlimb Muscle Atrophy Occurs From Short-Term Undernutrition in Rats
Authors: Kim Jee Yoon
Published: September 2012

The purpose of this study was to examine the effect of short-term (7 days) undernutrition on Type I (soleus) and Type II (plantaris, gastrocnemius) muscles in rats. Male Sprague-Dawley rats ( N = 20) were randomly assigned to one of two groups: a control group ( n = 10) in which animals were allowed to have water and pellets ad libitum and an undernourished group ( n = 10) in which animals were allowed to have 37% of the total food intake of the control group and water ad libitum. Body weight and food intake were measured daily. After 7 days, rats were anesthetized and the soleus, plantaris, and gastrocnemius muscles and liver were dissected. Body weight, liver weight, muscle weight, Types I and II fiber cross-sectional area, and myofibrillar protein content were determined. After 7 days of undernutrition, the undernourished group showed significant decreases ( p < .05) compared to the control group in body weight, liver weight, muscle weight of soleus, plantaris, and gastrocnemius muscles, and cross-sectional areas of Types I and II fiber of the plantaris and gastrocnemius muscles.
The Terrorist Attacks of 9/11 and the Financial Crisis of 2008
Authors: Kosová Renáta , Enz Cathy A.
Published: September 2012

The U.S. hotel industry faced two major external shocks in the decade of the 2000s, the terrorist attacks of September 11, 2001, and the financial crisis of September 2008, which led to an economic recession. Using data from STR covering nearly 35,000 hotels, this study isolates the specific effects of the two shocks by controlling for other market factors (e.g., inflation, seasonality) and hotel characteristics (e.g., hotel size, segment, or operation type) that affect a hotel’s daily operations. The study shows that hotels were significantly affected by both events, but they started to recover relatively quickly, within four months of each shock. Because of the nature of the shock, the 9/11 terrorist attacks had an abrupt and dramatic impact in reducing hotels’ occupancy, and rates briefly followed occupancy downward. The effects of the financial crisis took longer to develop but were less striking and apparently well handled by most hotel managers. Looking specifically at New York City’s hotels which stand next to ground zero for both shocks, the study found a pattern of occupancy, ADR, and RevPAR similar to that of the nation as a whole. New York’s luxury hotels felt the brunt of the shocks, but they were able to recover. Overall, the study paints a picture of an industry that maintains its ability to address the effects of environmental shocks, and focuses well on revenue management. Far from being in disarray, hotel management addressed the effects of these two shocks, as evidenced by the hotels’ recovery.
Fearless Improvisation
Authors: Alexander Michael L.
Published: September 2012

The purpose of this study was to investigate the confidence, anxiety, and attitude of novice string student improvisers. A form of the Fennema–Sherman Mathematics Attitudes Scales, as modified for improvisation by Wehr-Flowers, was given to middle school and high school string students ( N = 121) after their participation in a 4-month improvisation curriculum. Whereas females in Wehr-Flowers’s study were found to be significantly less confident than males in either study, the confidence level of females in the current study was not significantly different from any other group. Females in both studies were significantly more anxious toward improvisation than males, and the results of the attitude comparisons were inconclusive. The higher confidence level of females in the current study may have resulted from the different populations studied, maturation/history effects, or exposure to a curriculum specifically designed to build confidence and allay fears toward improvisation.
NPP4 is a procoagulant enzyme on the surface of vascular endothelium
Authors: Albright Ronald A. , Chang William C. , Robert Donna , Ornstein Deborah L. , Cao Wenxiang , Liu Lynn , Redick Meredith E. , Young J. Isaac , De La Cruz Enrique M. , Braddock Demetrios T.
Published: September 2012

Ap3A is a platelet-dense granule component released into the extracellular space during the second wave of platelet aggregation on activation. Here, we identify an uncharacterized enzyme, nucleotide pyrophosphatase/phosphodiesterase-4 (NPP4), as a potent hydrolase of Ap3A capable of stimulating platelet aggregation and secretion. We demonstrate that NPP4 is present on the surface of vascular endothelium, where it hydrolyzes Ap3A into AMP and ADP, and Ap4A into AMP and ATP. Platelet aggregation assays with citrated platelet-rich plasma reveal that the primary and secondary waves of aggregation and dense granule release are strongly induced by nanomolar NPP4 in a concentration-dependent manner in the presence of Ap3A, while Ap3A alone initiates a primary wave of aggregation followed by rapid disaggregation. NPP2 and an active site NPP4 mutant, neither of which appreciably hydrolyzes Ap3A, have no effect on platelet aggregation and secretion. Finally, by using ADP receptor blockade we confirm that NPP4 mediates platelet aggregation via release of ADP from Ap3A and activation of ADP receptors. Collectively, these studies define the biologic and enzymatic basis for NPP4 and Ap3A activity in platelet aggregation in vitro and suggest that NPP4 promotes hemostasis in vivo by augmenting ADP-mediated platelet aggregation at the site of vascular injury.
Dynamic clonal analysis of murine hematopoietic stem and progenitor cells marked by 5 fluorescent proteins using confocal and multiphoton microscopy
Authors: Malide Daniela , Métais Jean-Yves , Dunbar Cynthia E.
Published: September 2012

We demonstrate a methodology for tracing the clonal history of hematopoietic stem and progenitor cells (HSPCs) behavior in live tissues in 4 dimensions (4D). This integrates genetic combinatorial marking using lentiviral vectors encoding various fluorescent proteins (FPs) with advanced imaging methods. Five FPs: Cerulean, EGFP, Venus, tdTomato, and mCherry were concurrently used to create a diverse palette of color-marked cells. A key advantage of imaging using a confocal/2-photon hybrid microscopy approach is the simultaneous assessment of uniquely 5FP-marked cells in conjunction with structural components of the tissues at high resolution. Volumetric analyses revealed that spectrally coded HSPC-derived cells can be detected noninvasively in various intact tissues, including the bone marrow, for extensive periods of time after transplantation. Live studies combining video-rate multiphoton and confocal imaging in 4D demonstrate the possibility of dynamic cellular and clonal tracking in a quantitative manner. This methodology has applications in the understanding of clonal architecture in normal and perturbed hematopoiesis.
Use of tuberculin skin test, IFN-γ release assays and IFN-γ-induced protein-10 to identify children with TB infection
Authors: Yassin Mohammed A. , Petrucci Roberta , Garie Kefyalew T. , Harper Greg , Teshome Aklilo , Arbide Isabel , Asnake Girum , Ahmed Habiba J. , Mammo Tadesse , Yesuf Kedir , Cuevas Luis E.
Published: September 2012

Current tests of tuberculosis (TB) infection (tuberculin skin test (TST), interferon (IFN)-γ-release assays (IGRAs) and IFN-γ-induced protein (IP)-10) have limitations and their value when used consecutively to identify infected children has not been explored.

This study describes TST, IGRA and IP-10 responses in children in contact with adults with TB, the agreement of the tests and whether using multiple tests indentifies more infected children. 330 children (aged 1–15 yrs) in contact with adults with pulmonary TB and 156 controls were studied in Ethiopia.

Children exposed to adults with high bacilli grades in sputum were more likely to have positive TST, IFN-γ and IP-10 than controls. The agreement of positive tests was directly associated with the sputum bacilli grades (p<0.001 for all). The agreement of negative tests was higher in control children. The consecutive use of the tests increased the number of children classified as having at least one positive test.

Using three tests increases the number of children classified as infected. This increase is associated with the bacilli load of the adults. Using only one test may underestimate the proportion of infected children, but the interpretation of the data is difficult due to the lack of reference standards.
Confocal laser endomicroscopy for diagnosing lung cancerin vivo
Authors: Fuchs Florian S. , Zirlik Sabine , Hildner Kai , Schubert Juergen , Vieth Michael , Neurath Markus F.
Published: September 2012

Confocal laser endomicroscopy is a novel endoscopic technique that may allow imaging of living cells in lung tissuein vivo. We assessed the potential of this technique for the detection of histology during screening bronchoscopy for lung cancer.

32 patients with suspected malignancies underwent bronchoscopy with endomicroscopy using acriflavine hydrochloride. Standardised areas and localised lesions were analysed byin vivoconfocal imaging during bronchoscopy and biopsies were taken. Confocal images were graded and correlated prospectively with conventional histology from biopsies.

Acriflavine hydrochloride yielded high-quality confocal images and strongly labelled airway epithelial cells. No side-effects were noted. 75 522 confocal images from 56 different locations were compared prospectively with histological data from biopsy specimens. Endomicroscopy allowed subsurface imaging with detailed analysis of cellular and subcellular structures. Neoplastic changes could be predicted with high accuracy (sensitivity 96.0%, specificity 87.1%, accuracy 91.0%).

Confocal laser endomicroscopy with acriflavine is a novel diagnostic tool for the analysis of living cells during bronchoscopy and permits virtual histology of neoplastic changes in the airways with high accuracy. This technique may enable the rapid diagnosis of neoplasia during ongoing endoscopy in patients with suspected lung cancer.
Quality assessment of protein model-structures based on structural and functional similarities
Authors: Konopka Bogumil M , Nebel Jean-Christophe , Kotulska Malgorzata
Published: September 2012

Background

Experimental determination of protein 3D structures is expensive, time consuming and sometimes impossible. A gap between number of protein structures deposited in the World Wide Protein Data Bank and the number of sequenced proteins constantly broadens. Computational modeling is deemed to be one of the ways to deal with the problem. Although protein 3D structure prediction is a difficult task, many tools are available. These tools can model it from a sequence or partial structural information, e.g. contact maps. Consequently, biologists have the ability to generate automatically a putative 3D structure model of any protein. However, the main issue becomes evaluation of the model quality, which is one of the most important challenges of structural biology.

Results

GOBA - Gene Ontology-Based Assessment is a novel Protein Model Quality Assessment Program. It estimates the compatibility between a model-structure and its expected function. GOBA is based on the assumption that a high quality model is expected to be structurally similar to proteins functionally similar to the prediction target. Whereas DALI is used to measure structure similarity, protein functional similarity is quantified using standardized and hierarchical description of proteins provided by Gene Ontology combined with Wang's algorithm for calculating semantic similarity. Two approaches are proposed to express the quality of protein model-structures. One is a single model quality assessment method, the other is its modification, which provides a relative measure of model quality. Exhaustive evaluation is performed on data sets of model-structures submitted to the CASP8 and CASP9 contests.

Conclusions

The validation shows that the method is able to discriminate between good and bad model-structures. The best of tested GOBA scores achieved 0.74 and 0.8 as a mean Pearson correlation to the observed quality of models in our CASP8 and CASP9-based validation sets. GOBA also obtained the best result for two targets of CASP8, and one of CASP9, compared to the contest participants. Consequently, GOBA offers a novel single model quality assessment program that addresses the practical needs of biologists. In conjunction with other Model Quality Assessment Programs (MQAPs), it would prove useful for the evaluation of single protein models.
Pathogen-induced Caenorhabditis elegans developmental plasticity has a hormetic effect on the resistance to biotic and abiotic stresses
Authors: Leroy Magali , Mosser Thomas , Manière Xavier , Alvarez Diana Fernández , Matic Ivan
Published: September 2012

Background

Phenotypic plasticity, i.e. the capacity to change the phenotype in response to changes in the environment without alteration of the genotype, is important for coping with unstable environments. In spite of the ample evidence that microorganisms are a major environmental component playing a significant role in eukaryotic organisms health and disease, there is not much information about the effect of microorganism-induced developmental phenotypic plasticity on adult animals’ stress resistance and longevity.

Results

We examined the consequences of development ofCaenorhabditis eleganslarvae fed with different bacterial strains on stress resistance and lifespan of adult nematodes. Bacterial strains used in this study were either pathogenic or innocuous to nematodes. Exposure to the pathogen during development did not affect larval survival. However, the development of nematodes on the pathogenic bacterial strains increased lifespan of adult nematodes exposed to the same or a different pathogen. A longer nematode lifespan, developed on pathogens and exposed to pathogens as adults, did not result from an enhanced capacity to kill bacteria, but is likely due to an increased tolerance to the damage inflicted by the pathogenic bacteria. We observed that adult nematodes developed on a pathogen induce higher level of expression of thehsp-16.2gene and have higher resistance to heat shock than nematodes developed on an innocuous strain. Therefore, the increased resistance to pathogens could be, at least partially, due to the early induction of the heat shock response in nematodes developed on pathogens. The lifespan increase is controlled by the DBL-1 transforming growth factor beta-like, DAF-2/DAF-16 insulin-like, and p38 MAP kinase pathways. Therefore, the observed modulation of adult nematode lifespans by developmental exposure to a pathogen is likely a genetically controlled response.

Conclusions

Our study shows that development on pathogens has a hormetic effect on adult nematodes, as it results in increased resistance to different pathogens and to heat shock. Such developmental plasticity ofC. elegansnematodes, which are self-fertilizing homozygous animals producing offspring with negligible genetic variation, could increase the probability of survival in changing environments.
Evolutionary insights into scleractinian corals using comparative genomic hybridizations
Authors: Aranda Manuel , DeSalvo Michael K , Bayer Till , Medina Monica , Voolstra Christian R
Published: September 2012

Background

Coral reefs belong to the most ecologically and economically important ecosystems on our planet. Yet, they are under steady decline worldwide due to rising sea surface temperatures, disease, and pollution. Understanding the molecular impact of these stressors on different coral species is imperative in order to predict how coral populations will respond to this continued disturbance. The use of molecular tools such as microarrays has provided deep insight into the molecular stress response of corals. Here, we have performed comparative genomic hybridizations (CGH) with different coral species to an Acropora palmata microarray platform containing 13,546 cDNA clones in order to identify potentially rapidly evolving genes and to determine the suitability of existing microarray platforms for use in gene expression studies (via heterologous hybridization).

Results

Our results showed that the current microarray platform for A. palmata is able to provide biological relevant information for a wide variety of coral species covering both the complex clade as well the robust clade. Analysis of the fraction of highly diverged genes showed a significantly higher amount of genes without annotation corroborating previous findings that point towards a higher rate of divergence for taxonomically restricted genes. Among the genes with annotation, we found many mitochondrial genes to be highly diverged in M. faveolata when compared to A. palmata, while the majority of nuclear encoded genes maintained an average divergence rate.

Conclusions

The use of present microarray platforms for transcriptional analyses in different coral species will greatly enhance the understanding of the molecular basis of stress and health and highlight evolutionary differences between scleractinian coral species. On a genomic basis, we show that cDNA arrays can be used to identify patterns of divergence. Mitochondrion-encoded genes seem to have diverged faster than nuclear encoded genes in robust corals. Accordingly, this needs to be taken into account when using mitochondrial markers for scleractinian phylogenies.
Role of Helicobacter pylori
cagA EPIYA motif and vacAgenotypes for the development of gastrointestinal diseases in Southeast Asian countries: a meta-analysis
Authors: Sahara Shu , Sugimoto Mitsushige , Vilaichone Ratha-Korn , Mahachai Varocha , Miyajima Hiroaki , Furuta Takahisa , Yamaoka Yoshio
Published: September 2012

Background

Infection with cagA-positive, cagA EPIYA motif ABD type, and vacA s1, m1, and i1 genotype strains of Helicobacter pylori is associated with an exacerbated inflammatory response and increased risk of gastroduodenal diseases. However, it is unclear whether the prevalence and virulence factor genotypes found in Southeast Asia are similar to those in Western countries. Here, we examined the cagA status and prevalence of cagA EPIYA motifs and vacA genotypes among H. pylori strains found in Southeast Asia and examined their association with gastroduodenal disease.

Methods

To determine the cagA status, cagA EPIYA motifs, and vacA genotypes of H. pylori, we conducted meta-analyses of 13 previous reports for 1,281 H. pylori strains detected from several Southeast Asian countries.

Results

The respective frequencies of cagA-positive and vacA s1, m1, and i1 genotypes among examined subjects were 93% (1,056/1,133), 98% (1,010/1,033), 58% (581/1,009), and 96% (248/259), respectively. Stratification showed significant variation in the frequencies of cagA status and vacA genotypes among countries and the individual races residing within each respective country. The frequency of the vacA m-region genotype in patients infected with East Asian-type strains differed significantly between the northern and southern areas of Vietnam (p < 0.001). Infection with vacA m1 type or cagA-positive strains was associated with an increased risk of peptic ulcer disease (odds ratio: 1.46, 95%CI: 1.01-2.12, p = 0.046 and 2.83, 1.50-5.34, p = 0.001, respectively) in the examined Southeast Asian populations.

Conclusions

Both Western- and East Asian-type strains of H. pylori are found in Southeast Asia and are predominantly cagA-positive and vacA s1 type. In Southeast Asia, patients infected with vacA m1 type or cagA-positive strains have an increased risk of peptic ulcer disease. Thus, testing for this genotype and the presence of cagA may have clinical usefulness.
Mineral and bone disorder in Chinese dialysis patients: a multicenter study
Authors: Kong Xianglei , Zhang Luxia , Zhang Ling , Chen Nan , Gu Yong , Yu Xueqing , Liu Wenhu , Chen Jianghua , Peng Liren , Yuan Weijie , Wu Hua , Chen Wei , Fan Minhua , He Liqun , Ding Feng , Chen Xiangmei , Xiong Zuying , Zhang Jinyuan , Jia Qiang , Shi Wei , Xing Changying , Tang Xiaoling , Hou Fanfan , Shu Guiyang , Mei Changlin , Wang Li , Xu Dongmei , Ni Zhaohui , Zuo Li , Wang Mei , Wang Haiyan
Published: September 2012

Background

Mineral and bone disorder (MBD) in patients with chronic kidney disease is associated with increased morbidity and mortality. Studies regarding the status of MBD treatment in developing countries, especially in Chinese dialysis patients are extremely limited.

Methods

A cross-sectional study of 1711 haemodialysis (HD) patients and 363 peritoneal dialysis (PD) patients were enrolled. Parameters related to MBD, including serum phosphorus (P), calcium (Ca), intact parathyroid hormone (iPTH) were analyzed. The achievement of MBD targets was compared with the results from the Dialysis Outcomes and Practice Study (DOPPS) 3 and DOPPS 4. Factors associated with hyperphosphatemia were examined.

Results

Total 2074 dialysis patients from 28 hospitals were involved in this study. Only 38.5%, 39.6% and 26.6% of them met the Kidney Disease Outcomes Quality Initiative (K/DOQI) defined targets for serum P, Ca and iPTH levels. Serum P and Ca levels were statistically higher (P < 0.05) in the HD patients compared with those of PD patients, which was (6.3 ± 2.1) mg/dL vs (5.7 ± 2.0) mg/dL and (9.3 ± 1.1) mg/dL vs (9.2 ± 1.1) mg/dL, respectively. Serum iPTH level were statistically higher in the PD patients compared with those of HD patients (P = 0.03). The percentage of patients reached the K/DOQI targets for P (37.6% vs 49.8% vs 54.5%, P < 0.01), Ca (38.6% vs 50.4% vs 56.0%, P < 0.01) and iPTH (26.5% vs 31.4% vs 32.1%, P < 0.01) were lower among HD patients, compared with the data from DOPPS 3 and DOPPS 4. The percentage of patients with serum phosphorus level above 5.5 mg/dL was 57.4% in HD patients and 47.4% in PD patients. Age, dialysis patterns and region of residency were independently associated with hyperphosphatemia.

Conclusions

Status of MBD is sub-optimal among Chinese patients receiving dialysis. The issue of hyperphosphatemia is prominent and needs further attention.
Mono- and combination drug therapies in hospitalized patients with bipolar depression. Data from the European drug surveillance program AMSP
Authors: Haeberle Anne , Greil Waldemar , Russmann Stefan , Grohmann Renate
Published: September 2012

Background

For the pharmacological treatment of bipolar depression several guidelines exist. It is largely unknown, to what extent the prescriptions in daily clinical routine correspond to these evidence based recommendations and which combinations of psychotropic drugs are frequently used.

Methods

The prescriptions of psychotropic drugs were investigated of all in-patients with bipolar depression (n = 2246; time period 1994–2009) from hospitals participating in the drug surveillance program AMSP. For the drug use in 2010, 221 cases were analysed additionally.

Results

From 1994 to 2009, 85% of all patients received more than one class of psychotropic substances: 74% received antidepressants in combination therapy, 55% antipsychotics, 48% anticonvulsants and 33% lithium. When given in combination, lithium is the most often prescribed substance for bipolar depression (33%), followed by valproic acid (23%), mirtazapine and venlafaxine (16% each), quetiapine (15%), lamotrigine (14%) and olanzapine (13%). Both, lithium and valproic acid are often combined with selective serotonin reuptake inhibitors (SSRI), but also with mirtazapine und venlafaxine. Combinations of more than one antidepressant occur quite often, whereby combinations with bupropion, paroxetine, fluoxetine or fluvoxamine are very rare. In 2010, quetiapine (alone and combined) was the most frequently prescribed drug (39%); aripiprazole was administered in 10%.

Conclusion

Combinations of antidepressants (SSRI, mirtazapine, venlafaxine) with mood stabilizers (lithium, valproic acid, lamotrigine) and / or atypical antipsychotics (quetiapine, olanzapine) are common. Of most of those combinations the efficacy has not been studied. The use of aripiprazole and the concomitant use of two or three antidepressants contrast the guidelines.
A single-nucleotide polymorphism rs708567 in the IL-17RC gene is associated with a susceptibility to and the curve severity of adolescent idiopathic scoliosis in a Chinese Han population: a case-control study
Authors: Zhou Song , Qiu Xu-sheng , Zhu Ze-zhang , Wu Wei-fei , Liu Zhen , Qiu Yong
Published: September 2012

Background

Although the pathogenesis of adolescent idiopathic scoliosis (AIS) remains controversial, genetic factors are thought to play key roles in the development of AIS. In a recent genome-wide association study, a polymorphism in the interleukin-17 receptor C (IL-17RC) gene was reported to be associated with the susceptibility to AIS, implicating IL-17RC as a novel predisposing gene for AIS. However, as this association has not been replicated in other populations, its global applicability remains unclear.

Methods

A total of 529 Chinese girls with AIS and 512 healthy age-matched controls were recruited in this case–control study from June 2007 to December 2009. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect the genotype of the single-nucleotide polymorphism (SNP) rs708567 in the IL-17RC gene. Case–control and case-only studies were performed to determine the association between the IL-17RC gene polymorphism and the susceptibility to and curve severity of AIS.

Results

The GG genotype and G allele frequencies were significantly higher in the AIS patients than in the controls (χ
2 test: P = 0.023 and 0.028, respectively). The risk for the GG genotype is 1.550-fold (95% CI: 1.062 - 2.261) higher than the AG genotype, and the risk for the G allele is 1.507-fold (95% CI: 1.046 - 2.172) higher than the A allele. Additionally, a subgroup of skeletally mature AIS patients (n = 241) who carried the GG genotype showed a significantly higher mean maximum Cobb angle than those carrying the AG genotype (36.01 ± 13.12° vs. 28.92 ± 7.43°, P = 0.007).

Conclusions

This study confirms the significant association between the IL-17RC gene polymorphism and the susceptibility to and curve severity of AIS in a Chinese Han population, suggesting that the IL-17RC gene is an AIS-predisposing gene in Chinese Han population.
Hybrid gold-iron oxide nanoparticles as a multifunctional platform for biomedical application
Authors: Hoskins Clare , Min Yue , Gueorguieva Mariana , McDougall Craig , Volovick Alexander , Prentice Paul , Wang Zhigang , Melzer Andreas , Cuschieri Alfred , Wang Lijun
Published: September 2012

Background

Iron oxide nanoparticles (IONPs) have increasing applications in biomedicine, however fears over long term stability of polymer coated particles have arisen. Gold coating IONPs results in particles of increased stability and robustness. The unique properties of both the iron oxide (magnetic) and gold (surface plasmon resonance) result in a multimodal platform for use as MRI contrast agents and as a nano-heater.

Results

Here we synthesize IONPs of core diameter 30 nm and gold coat using the seeding method with a poly(ethylenimine) intermediate layer. The final particles were coated in poly(ethylene glycol) to ensure biocompatibility and increase retention times in vivo. The particle coating was monitored using FTIR, PCS, UV–vis absorption, TEM, and EDX. The particles appeared to have little cytotoxic effect when incubated with A375M cells. The resultant hybrid nanoparticles (HNPs) possessed a maximal absorbance at 600 nm. After laser irradiation in agar phantom a ΔT of 32°C was achieved after only 90 s exposure (50 μgmL-1). The HNPs appeared to decrease T2 values in line with previously clinically used MRI contrast agent Feridex®.

Conclusions

The data highlights the potential of these HNPs as dual function MRI contrast agents and nano-heaters for therapies such as cellular hyperthermia or thermo-responsive drug delivery.
Preoperative Cyfra21-1 and SCC-Ag serum titers predict survival in patients with stage II esophageal squamous cell carcinoma
Authors: Cao Xun , Zhang Lin , Feng Gui-Rong , Yang Juan , Wang Ruo-Yan , Li Jun , Zheng Xiao-Min , Han Yu-Jing
Published: September 2012

Background

The purpose of this study is to evaluate the predictive significance of preoperative serum level of cytokeratin 19 fragments (Cyfra21-1) and squamous cell carcinoma antigen (SCC-Ag) after complete resection in patients with stage II esophageal squamous cell carcinoma (ESCC).

Methods

Between 1995 and 2006, a total of 379 patients in stage II ESCC who underwent complete resection were consecutively recruited. Statistical analyses were applied to test the associations between preoperative serum titers of Cyfra21-1 and SCC-Ag, clinicopathological factors and prognoses.

Results

Preoperative high and normal serum level of Cyfra21-1 and SCC-Ag were found in 47.8%, 52.2% and 72.8%, 27.2%, respectively. The 1-, 3-, 5-year overall survival rate for the entire cohort of patients was 95%, 78%, and 56%, respectively. Median overall survival (OS) was 45.3 months longer in patients with low preoperative serum level of Cyfra21-1 (91.9 months) than those with high preoperative serum level of Cyfra21-1 (46.6 months) (P < 0.001). Median OS among patients with SCC-Ag-low level was also longer than those with SCC-Ag-high level (89.7 vs. 63.7 months, P < 0.001), especially for those with stage IIB (P < 0.001). After multivariate analysis, along with pTNM stage, preoperative serum level of Cyfra21-1 and SCC-Ag were independently and significantly predictive factors (P < 0.001, P < 0.001). Furthermore, the five-year survival rate in double-low subset, either-low subset and double-high subset was 100%, 83% and 27%, respectively (P < 0.001).

Conclusions

The preoperative serum level of Cyfra21-1 and SCC-Ag are independently significant predictors which negatively affected the survivals of patients with stage II ESCC.
RETRACTED ARTICLE: Alteration of astrocytes and Wnt/β-catenin signaling in the frontal cortex of autistic subjects
Authors: Cao Fujiang , Yin Ailan , Wen Guang , Sheikh Ashfaq M , Tauqeer Zujaja , Malik Mazhar , Nagori Amenah , Schirripa Michael , Schirripa Frank , Merz George , Ted Brown W , Li Xiaohong
Published: September 2012

Background

Autism is a neurodevelopmental disorder characterized by impairments in social interaction, verbal communication and repetitive behaviors. To date the etiology of this disorder is poorly understood. Studies suggest that astrocytes play critical roles in neural plasticity by detecting neuronal activity and modulating neuronal networks. Recently, a number of studies suggested that an abnormal function of glia/astrocytes may be involved in the development of autism. However, there is yet no direct evidence showing how astrocytes develop in the brain of autistic individuals.

Methods

Study subjects include brain tissue from autistic subjects, BTBR T + tfJ (BTBR) and Neuroligin (NL)-3 knock-down mice. Western blot analysis, Immunohistochemistry and confocal microscopy studies have be used to examine the density and morphology of astrocytes, as well as Wnt and β-catenin protein expression.

Results

In this study, we demonstrate that the astrocytes in autisitcsubjects exhibit significantly reduced branching processes, total branching length and cell body sizes. We also detected an astrocytosis in the frontal cortex of autistic subjects. In addition, we found that the astrocytes in the brain of anNL3knockdown mouse exhibited similar alterations to what we found in the autistic brain. Furthermore, we detected that both Wnt and β-catenin proteins are decreased in the frontal cortex of autistic subjects. Wnt/β-catenin pathway has been suggested to be involved in the regulation of astrocyte development.

Conclusions

Our findings imply that defects in astrocytes could impair neuronal plasticity and partially contribute to the development of autistic-like behaviors in both humans and mice. The alteration of Wnt/β-catenin pathway in the brain of autistic subjects may contribute to the changes of astrocytes.
Prevalence of amino acid mutations in hepatitis C virus core and NS5B regions among Venezuelan viral isolates and comparison with worldwide isolates
Authors: Jaspe Rossana C , Sulbarán Yoneira F , Sulbarán Maria Z , Loureiro Carmen L , Rangel Hector R , Pujol Flor H
Published: September 2012

Background

Recent reports show that R70Q and L/C91M amino acid substitutions in the core from different hepatitis C virus (HCV) genotypes have been associated with variable responses to interferon (IFN) and ribavirin (RBV) therapy, as well to an increase of hepatocellular carcinoma (HCC) risk, liver steatosis and insulin resistance (IR). Mutations in NS5B have also been associated to IFN, RBV, nucleoside and non-nucleoside inhibitors drug resistance. The prevalence of these mutations was studied in HCV RNA samples from chronically HCV-infected drug-naïve patients.

Methods

After amplification of core and NS5B region by nested-PCR, 12 substitutions were analyzed in 266 Venezuelan HCV isolates subtype 1a, 1b, 2a, 2c, 2b, 2j (a subtype frequently found in Venezuela) and 3a (n = 127 and n = 228 for core and NS5B respectively), and compared to isolates from other countries (n = 355 and n = 646 for core and NS5B respectively).

Results

R70Q and L/C91M core substitutions were present exclusively in HCV G1b. Both substitutions were more frequent in American isolates compared to Asian ones (69% versus 26%, p < 0.001 and 75% versus 45%, p < 0.001 respectively). In Venezuelan isolates NS5B D310N substitution was detected mainly in G3a (100%) and G1a (13%), this later with a significantly higher prevalence than in Brazilian isolates (p = 0.03). The NS5B mutations related to IFN/RBV treatment D244N was mainly found in G3a, and Q309R was present in all genotypes, except G2. Resistance to new NS5B inhibitors (C316N) was only detected in 18% of G1b, with a significantly lower prevalence than in Asian isolates, where this polymorphism was surprisingly frequent (p < 0.001).

Conclusions

Genotypical, geographical and regional differences were found in the prevalence of substitutions in HCV core and NS5B proteins. The substitutions found in the Venezuelan G2j type were similar to that found in G2a and G2c isolates. Our results suggest a high prevalence of the R70Q and L/C91M mutations of core protein for G1b and D310N substitution of NS5B protein for the G3a. C316N polymorphism related with resistance to new NS5B inhibitors was only found in G1b. Some of these mutations could be associated with a worse prognosis of the disease in HCV infected patients.
Positive Allosteric Modulation of TRPV1 as a Novel Analgesic Mechanism
Authors: Lebovitz Evan E , Keller Jason M , Kominsky Hal , Kaszas Krisztian , Maric Dragan , Iadarola Michael J
Published: September 2012

Background:

The prevalence of long-term opiate use in treating chronic non-cancer pain is increasing, and prescription opioid abuse and dependence are a major public health concern. To explore alternatives to opioid-based analgesia, the present study investigates a novel allosteric pharmacological approach operating through the cation channel TRPV1. This channel is highly expressed in subpopulations of primary afferent unmyelinated C- and lightly-myelinated Aδ-fibers that detect low and high rates of noxious heating, respectively, and it is also activated by vanilloid agonists and low pH. Sufficient doses of exogenous vanilloid agonists, such as capsaicin or resiniferatoxin, can inactivate/deactivate primary afferent endings due to calcium overload, and we hypothesized that positive allosteric modulation of agonist-activated TRPV1 could produce a selective, temporary inactivation of nociceptive nerve terminals in vivo. We previously identified MRS1477, a 1,4-dihydropyridine that potentiates vanilloid and pH activation of TRPV1 in vitro, but displays no detectable intrinsic agonist activity of its own. To study the in vivo effects of MRS1477, we injected the hind paws of rats with a non-deactivating dose of capsaicin, MRS1477, or the combination. An infrared diode laser was used to stimulate TRPV1-expressing nerve terminals and the latency and intensity of paw withdrawal responses were recorded. qRT-PCR and immunohistochemistry were performed on dorsal root ganglia to examine changes in gene expression and the cellular specificity of such changes following treatment.

Results:

Withdrawal responses of the capsaicin-only or MRS1477-only treated paws were not significantly different from the untreated, contralateral paws. However, rats treated with the combination of capsaicin and MRS1477 exhibited increased withdrawal latency and decreased response intensity consistent with agonist potentiation and inactivation or lesion of TRPV1-containing nerve terminals. The loss of nerve endings was manifested by an increase in levels of axotomy markers assessed by qRT-PCR and colocalization of ATF3 in TRPV1+ cells visualized via immunohistochemistry.

Conclusions:

The present observations suggest a novel, non-narcotic, selective, long-lasting TRPV1-based approach for analgesia that may be effective in acute, persistent, or chronic pain disorders.
Primary micro neuroendocrine tumor arising in a horseshoe kidney with cyst: report of a case and review of literature
Authors: Zhang Qingfu , Ming Jian , Zhang Siyang , Qiu Xueshan
Published: September 2012

Neuroendocrine tumors are a heterogeneous group of neoplasms that arise from neuroendocrine cells. Primary renal neuroendocrine tumors are among the most unusual of all renal neoplasms, since neuroendocrine cells are not found within normal renal parenchyma. Here, a case of primary micro neuroendocrine tumor (about 4.7 mm*2 mm) arising in the horseshoe kidney with a cyst of a 45-year-old man was reported and a literature review was written.

Virtual Slides

The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/2121156944757267
Folk taxonomy and use of mushrooms in communities around Ngorongoro and Serengeti National Park, Tanzania
Authors: Tibuhwa Donatha Damian
Published: September 2012

Background

Maasai and Kurya form two main communities around the Serengeti National Park in Tanzania which are mainly pastoralists. Changing climate to excessive drought, have recently forced them to start practicing subsistence farming which is severely affected by wild animals. This study explored status of the folk taxonomy and uses of mushrooms in the two communities as a pave way for possibilities of introducing mushroom cultivation, an alternative crop which is hardly affected by wild animals.

Methods

Folk taxonomy and use mushrooms by the Kurya and Maasai communities were investigated. Information was collected by face to face interviews with 150 individuals in 6 selected villages. Using descriptive statistics by Statistic Package for the Social Science (SPSS) version 17.0, the demographic characteristics of informants were evaluated and cross relationships with the recorded data were analysed.

Results

Kurya are mycophilic with 94% of the informants recognizing utilization of the wild mushroom either as foodstuff or as tonics while the Maasai are mycophobic with 99% being unaware of the edibility of mushroom although 28% recognized mushrooms as tonic. For both communities, the knowledge of mushroom utilization and folk taxonomy increased with age of the informants, while it decreases with formal education level of the informants which imply that the basis of knowledge is mainly traditional. Comparing the two communities, the Maasai use mushrooms only for medicinal purposes and never sought them for food while the Kurya were well knowledgeable on the edibility and folk classification especially the Termitomyces species. Characters used in folkal taxonomy included color and size of the basidiomata, shape and size of the pseudorrhiza, habitats and edibility information. A new use of ascospores whereby they anaesthaesia bees during honey harvesting was discovered, and mushroom cultivation was widely welcomed (94.7%) as an alternative crop which is rarely affected by wild animals.

Conclusion

In order to salvage a noted tremendous decrease of knowledge in mushroom utilization and folk taxonomy from vanishing, there is a need to document it throughout, and incorporate it in lower levels of our education system. Mushroom cultivation may possibly be the best alternative crop for the two communities thus should be advocated for improving livelihood and reduce human wildlife conflicts. The new recorded use of ascospores to anaesthaesia the bees during honey harvesting should be exploited and scaled up for sustainable integrated bee keeping and mushroom farming.
Application of Regent mechanical valve in patients with small aortic annulus: 3-year follow-up
Authors: Zhao Dong , Wang Chunsheng , Hong Tao , Pan Cuizhen , Guo Changfa
Published: September 2012

Background

Aortic valve replacement (AVR) with a small aortic annulus is always challenging for the cardiac surgeon. In this study, we sought to evaluate the midterm performance of implantation with a 17-mm or 19-mm St. Jude Medical Regent (SJM Regent) mechanical valve in retrospective consecutive cohort of patients with small aortic annulus (diameter ≤ 19 mm).

Methods

From January 2008 to April 2011, 40 patients (31 female, mean age = 47.2 ± 5.8 years) with small aortic annulus (≤19 mm in diameter) underwent aortic valve replacement with a 17-mm or 19-mm St. Jude Medical Regent (SJM Regent) mechanical valve. Preoperative mean body surface area, New York Heart Association class, and mean aortic annulus were 1.61 ± 0.26 m2, 3.2 ± 0.4, and 18 ± 1.4 mm respectively. Patients were divided into two groups, according to the implantation of 17 mm SJM Regent mechanical valve (group 1, n = 18) or 19 mm SJM Regent valve (group 2, n = 22). All patients underwent echocardiography examination preoperatively and at one year post-operation.

Results

There were no early deaths in either group. Follow-up time averaged 36 ± 17.6 months. The mean postoperative New York Heart Association class was 1.3 ± 0.6 (p < 0.001). By echocardiography, in group 1, the left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and the indexed effective orifice area (EOAI) increased from 43.7% ± 11.6%, 27.3% ± 7.6%, and 0.70 ± 0.06 cm2/m2 to 69.8 ± 9.3%, 41.4 ± 8.3%, and 0.92 ± 0.10 cm2/m2 respectively (P < 0.05), while the left ventricular mass index (LVMI), and the aortic transvalvular pressure gradient decreased from 116.4 ± 25.4 g/m2, 46.1 ± 8.5 mmHg to 86.7 ± 18.2 g/m2 , 13.7 ± 5.2 mmHg respectively. In group 2, the LVEF, LVFS and EOAI increased from 45.9% ± 9.7%, 30.7% ± 8.0%, and 0.81 ± 0.09 cm2/m2 to 77.4% ± 9.7%, 44.5% ± 9.6%, and 1.27 ± 0.11 cm2/m2 respectively, while the LVMI, and the aortic transvalvular pressure gradient decreased from 118.3 ± 27.6 g/m2, 44.0 ± 6.7 mmHg to 80.1 ± 19.7 g/m2, 10.8 ± 4.1 mmHg as well. The prevalence of PPM was documented in 2 patients in Group 1.

Conclusions

Patients with small aortic annulus and body surface area, experienced satisfactory clinical improvement after aortic valve replacement with modern SJM Regent bileaflet prostheses.
Macroautophagy deficiency mediates age-dependent neurodegeneration through a phospho-tau pathway
Authors: Inoue Keiichi , Rispoli Joanne , Kaphzan Hanoch , Klann Eric , Chen Emily I , Kim Jongpil , Komatsu Masaaki , Abeliovich Asa
Published: September 2012

Background

Macroautophagy is an evolutionarily conserved mechanism for bulk intracellular degradation of proteins and organelles. Pathological studies have implicated macroautophagy defects in human neurodegenerative disorders of aging including Alzheimer’s disease and tauopathies. Neuronal deficiency of macroautophagy throughout mouse embryonic development results in neurodevelopmental defects and early postnatal mortality. However, the role of macroautophagy in mature CNS neurons, and the relationship with human disease neuropathology, remains unclear. Here we describe mice deficient in an essential macroautophagy component, Atg7, specifically within postnatal CNS neurons.

Results

Postnatal forebrain-specific Atg7 conditional knockout (cKO) mice displayed age-dependent neurodegeneration and ubiquitin- and p62-positive inclusions. Phosphorylated tau was significantly accumulated in Atg7 cKO brains, but neurofibrillary tangles that typify end-stage human tauopathy were not apparent. A major tau kinase, glycogen synthase kinase 3β (GSK3β), was also accumulated in Atg7 cKO brains. Chronic pharmacological inhibition of tau phosphorylation, or genetic deletion of tau, significantly rescued Atg7-deficiency-mediated neurodegeneration, but did not suppress inclusion formation.

Conclusions

These data elucidate a role for macroautophagy in the long-term survival and physiological function of adult CNS neurons. Neurodegeneration in the context of macroautophagy deficiency is mediated through a phospho-tau pathway.