bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ephrin-A1 inhibits NSCLC tumor growth via induction of Cdx-2 a tumor suppressor gene
Authors: Sukka-Ganesh Bhagyalaxmi , Mohammed Kamal A , Kaye Frederic , Goldberg Eugene P , Nasreen Najmunnisa 
Published: July 2012

Abstract

Background
Tumor formation is a complex process which involves constitutive activation of oncogenes and suppression of tumor suppressor genes. Receptor EphA2 and its ligand ephrin-A1 form an important cell communication system with its functional role in cell-cell interaction and tumor growth. Loss of cell-cell adhesion is central to the cellular transformation and acquisition of metastatic potential. Claudins, the integrated tight junction (TJ) cell-cell adhesion proteins located on the apico-lateral portion of epithelial cells, functions in maintaining cell polarity. There is extensive evidence implicating Eph receptors and ephrins in malignancy, but the mechanisms how these molecular players affect TJ proteins and regulate tumor growth are not clear. In the present study we hypothesized that EphA2 signaling modulates claudin-2 gene expression via induction of cdx-2, a tumor suppressor gene in NSCLC cells.

Methods
The expression of EphA2, claudin-2 was determined in various NSCLC cell lines by using real-time quantitative polymerase chain reaction and Western blot analysis. The claudin-2 expression was also analyzed by immunofluorescence analysis. EphA2 and erk1/erk2 phosphorylation in ephrin-A1 activated cells was evaluated by Western blot analysis. The cell proliferation and tumor colony formation were determined by WST-1 and 3-D matrigel assays respectively.

Results
NSCLC cells over expressed receptor EphA2 and claudin-2. Ephrin-A1 treatment significantly down regulated the claudin-2 and EphA2 expression in NSCLC cells. The transient transfection of cells with vector containing ephrin-A1 construct (pcDNA-EFNA1) decreased the expression of claudin-2, EphA2 when compared to empty vector. In addition ephrin-A1 activation increased cdx-2 expression in A549 cells. In contrast over-expression of EphA2 with plasmid pcDNA-EphA2 up regulated claudin-2 mRNA expression and decreased cdx-2 expression. The transient transfection of cells with vector containing cdx-2 construct (pcMV-cdx-2) decreased the expression of claudin-2 in A549 cells. Moreover, silencing the expression of receptor EphA2 by siRNA significantly reduced claudin-2 expression and decreased cell proliferation and tumor formation. Furthermore, silencing cdx-2 gene expression before ephrin-A1 treatment increased claudin-2 expression along with increased cell proliferation and tumor growth in A549 cells.

Conclusions
Our study suggests that EphA2 signaling up-regulates the expression of the TJ-protein claudin-2 that plays an important role in promoting cell proliferation and tumor growth in NSCLC cells. We conclude that receptor EphA2 activation by ephrin-A1 induces tumor suppressor gene cdx-2 expression which attenuates cell proliferation, tumor growth and thus may be a promising therapeutic target against NSCLC.
The relationship between attention deficit hyperactivity disorder and premature infants in Taiwanese: a case control study
Authors: Chu Shih-Ming , Tsai Ming-Horng , Hwang Fan-Ming , Hsu Jen-Fu , Huang Hsuan Rong , Huang Yu-Shu 
Published: July 2012

Abstract

Background
Preterm survivors from the neonatal intensive care unit (NICU) are considered to be at risk for some neurobehavioral disorders such as attention-deficit/hyperactivity disorder (ADHD). The current study aimed to explore the relationship between ADHD and premature infants in Taiwan.

Methods
A total of 195 children (157 males and 38 females) diagnosed with ADHD based on DSM-IV and aged between 6 to 12 years and a control group of 212 (164 males, 48 females) age- and sex-matched healthy children were enrolled. The ADHD-Rating scale and CGI severity were performed by child psychiatrists. Demographic data of the children, including birth history, perinatal neurological and respiratory problems were collected to facilitate the investigation of whether a correlation exists between ADHD and prematurity.

Results
The ADHD group had a significantly higher rate of prematurity and significantly higher rate of low birth body weight (defined as <2500 g) than the control group (both P = 0.003). Pearson correlation showed a significantly negative correlation between gestational age and ADHD-RS score, inattentive score, hyperactivity and CGI-S score (P = 0.004, 0.013, 0.015 and 0.002, respectively). However, only a CGI-S score (P = 0.018) showed a significantly correlation between low birth weight and ADHD.

Conclusions
Premature infants have significantly more severe symptoms of ADHD at school age and they were highly correlated. Further study is necessary to determine the main effect and pathogenesis of moderate as well as extreme preterm birth on the development of ADHD.
Spatial clusters of suicide in Australia
Authors: Qi Xin , Hu Wenbiao , Page Andrew , Tong Shilu 
Published: July 2012

Abstract

Background
Understanding the spatial distribution of suicide can inform the planning, implementation and evaluation of suicide prevention activity. This study explored spatial clusters of suicide in Australia, and investigated likely socio-demographic determinants of these clusters.

Methods
National suicide and population data at a statistical local area (SLA) level were obtained from the Australian Bureau of Statistics for the period of 1999 to 2003. Standardised mortality ratios (SMR) were calculated at the SLA level, and Geographic Information System (GIS) techniques were applied to investigate the geographical distribution of suicides and detect clusters of high risk in Australia.

Results
Male suicide incidence was relatively high in the northeast of Australia, and parts of the east coast, central and southeast inland, compared with the national average. Among the total male population and males aged 15 to 34, Mornington Shire had the whole or a part of primary high risk cluster for suicide, followed by the Bathurst-Melville area, one of the secondary clusters in the north coastal area of the Northern Territory. Other secondary clusters changed with the selection of cluster radius and age group. For males aged 35 to 54 years, only one cluster in the east of the country was identified. There was only one significant female suicide cluster near Melbourne while other SLAs had very few female suicide cases and were not identified as clusters. Male suicide clusters had a higher proportion of Indigenous population and lower median socio-economic index for area (SEIFA) than the national average, but their shapes changed with selection of maximum cluster radii setting.

Conclusion
This study found high suicide risk clusters at the SLA level in Australia, which appeared to be associated with lower median socio-economic status and higher proportion of Indigenous population. Future suicide prevention programs should focus on these high risk areas.
Spatial-temporal analysis of malaria and the effect of environmental factors on its incidence in Yongcheng, China, 2006–2010
Authors: Zhang Yan , Liu Qi-Yong , Luan Rong-Sheng , Liu Xiao-Bo , Zhou Guang-Chao , Jiang Jing-Yi , Li Hong-Sheng , Li Zhi-Fang 
Published: July 2012

Abstract

Background
In 2003, Plasmodium vivax malaria has re-emerged in central eastern China including Yongcheng prefecture, Henan Province, where no case has been reported for eleven years. Our goals were to detect the space-time distribution pattern of malaria and to determine significant environmental variables contributing to malaria incidence in Yongcheng from 2006 to 2010, thus providing scientific basis for further optimizing current malaria surveillance and control programs.

Methods
This study examined the spatial and temporal heterogeneities in the risk of malaria and the influencing factors on malaria incidence using geographical information system (GIS) and time series analysis. Univariate analysis was conducted to estimate the crude correlations between malaria incidence and environmental variables, such as mosquito abundance and climatic factors. Multivariate analysis was implemented to construct predictive models to explore the principal environmental determinants on malaria epidemic using a Generalized Estimating Equation (GEE) approach.

Results
Annual malaria incidence at town-level decreased from the north to south, and monthly incidence at prefecture-level demonstrated a strong seasonal pattern with a peak from July to November. Yearly malaria incidence had a visual spatial association with yearly average temperature. Moreover, the best-fit temporal model (model 2) (QIC = 16.934, P<0.001, R2 = 0.818) indicated that significant factors contributing to malaria incidence were maximum temperature at one month lag, average humidity at one month lag, and malaria incidence of the previous month.

Conclusions
Findings supported the effects of environment factors on malaria incidence and indicated that malaria control targets should vary with intensity of malaria incidence, with more public resource allocated to control the source of infections instead of large scale An. sinensis control when malaria incidence was at a low level, which would benefit for optimizing the malaria surveillance project in China and some other countries with unstable or low malaria transmission.
Oxidative stress mediated arterial dysfunction in patients with obstructive sleep apnoea and the effect of continuous positive airway pressure treatment
Authors: Del Ben Maria , Fabiani Mario , Loffredo Lorenzo , Polimeni Licia , Carnevale Roberto , Baratta Francesco , Brunori Marco , Albanese Fabiana , Augelletti Teresa , Violi Francesco , Angelico Francesco 
Published: July 2012

Abstract

Background
Several studies suggest an increase of oxidative stress and a reduction of endothelial function in obstructive sleep apnoea syndrome (OSAS). We assessed the association between OSAS, endothelial dysfunction and oxidative stress. Further aim was to evaluate the effect of nasal continuous positive airway pressure (nCPAP) on oxidative stress and arterial dysfunction.

Methods
We studied 138 consecutive patients with heavy snoring and possible OSAS. Patients underwent unattended overnight home polysomnography. Ten patients with severe OSAS were revaluated after 6 months of nCPAP therapy. To assess oxidative stress in vivo, we measured urinary 8-iso-PGF2α and serum levels of soluble NOX2-derived peptide (sNOX2-dp). Serum levels of nitrite/nitrate (NOx) were also determined. Flow-mediated brachial artery dilation (FMD) was measured to asses endothelial function.

Results
Patients with severe OSAS had higher urinary 8-iso-PGF2α (p<0.001) and serum NOX2 and lower NOx. A negative association was observed between FMD and OSA severity. Apnea/hypopnea index was significantly correlated with the indices of central obesity and with urinary 8-isoprostanes (r=0.298, p<0.001). The metabolic syndrome (t=-4.63, p<0.001) and urinary 8-isoprostanes (t=-2.02, p<0.05) were the only independent predictors of FMD. After 6-months nCPAP treatment, a significant decrease of serum NOX2, (p<0.005) and urinary 8-iso-PGF2α (p<0.01) was observed, while serum NOx showed only a minor increase. A statistically significant increase of FMD was observed (from 3.6% to 7.0%).

Conclusions
The results of our study indicate that patients with OSAS and cardiometabolic comorbidities have increased oxidative stress and arterial dysfunction that are partially reversed by nCPAP treatment.
Whole plant based treatment of hypercholesterolemia with Crataegus laevigata in a zebrafish model
Authors: Littleton Robert M , Miller Matthew , Hove Jay R 
Published: July 2012

Abstract

Background
Consumers are increasingly turning to plant-based complementary and alternative medicines to treat hypercholesterolemia. Many of these treatments are untested and their efficacy is unknown. This multitude of potential remedies necessitates a model system amenable to testing large numbers of organisms that maintains similarity to humans in both mode of drug administration and overall physiology. Here we develop the larval zebrafish (4–30 days post fertilization) as a vertebrate model of dietary plant-based treatment of hypercholesterolemia and test the effects of Crataegus laevigata in this model.

Methods
Larval zebrafish were fed high cholesterol diets infused with fluorescent sterols and phytomedicines. Plants were ground with mortar and pestle into a fine powder before addition to food. Fluorescent sterols were utilized to optically quantify relative difference in intravascular cholesterol levels between groups of fish. We utilized the Zeiss 7-Live Duo high-speed confocal platform in order to both quantify intravascular sterol fluorescence and to capture video of the heart beat for determination of cardiac output.

Results
In this investigation we developed and utilized a larval zebrafish model to investigate dietary plant-based intervention of the pathophysiology of hypercholesterolemia. We found BODIPY-cholesterol effectively labels diet-introduced intravascular cholesterol levels (P < 0.05, Student’s t-test). We also established that zebrafish cardiac output declines as cholesterol dose increases (difference between 0.1% and 8% (w/w) high cholesterol diet-treated cardiac output significant at P < 0.05, 1-way ANOVA). Using this model, we found hawthorn leaves and flowers significantly reduce intravascular cholesterol levels (P < 0.05, 1-way ANOVA) and interact with cholesterol to impact cardiac output in hypercholesterolemic fish (2-way ANOVA, P < 0.05 for interaction effect).

Conclusions
The results of this study demonstrate that the larval zebrafish has the potential to become a powerful model to test plant based dietary intervention of hypercholesterolemia. Using this model we have shown that hawthorn leaves and flowers have the potential to affect cardiac output as well as intravascular cholesterol levels. Further, our observation that hawthorn leaves and flowers interact with cholesterol to impact cardiac output indicates that the physiological effects of hawthorn may depend on diet.
Community based study to compare the incidence and health services utilization pyramid for gastrointestinal, respiratory and dermal symptoms
Authors: Najnin Nusrat , Sinclair Martha , Forbes Andrew , Leder Karin 
Published: July 2012

Abstract

Background
Gastrointestinal (GI), respiratory and dermal symptoms are common and cause substantial morbidity, although the information on their exact incidence and comparative burden is limited. The aim of this study was to describe the epidemiology and rate these three major symptom complexes in order to improve our understanding of the health burden imposed by these symptoms.

Methods
We used data from a community based randomised control trial conducted from June 2007 to August 2008 among 277 South Australian families consuming rainwater. Using weekly health diaries, we prospectively collected information on GI (diarrhoea or vomiting), respiratory (sore throat, runny nose or cough) and dermal (rash, generalised itch or dermal infection) symptoms, as well as on relevant GP visits, time off work and/or hospitalisation due to these symptoms. Data were analysed using generalized estimating equations approach taking into account the variable number of weeks of follow-up of each individual and within-family clustering of responses.

Results
Over one year, at least one episode of GI symptoms was reported by 54% of participants (95% CI 50%-58%), at least one respiratory episode by 91% (95% CI 88%-93%) and at least one episode of dermal symptoms by 27% (95% CI 24%-30%). The average number of weeks per year during which respiratory symptoms occurred was four times greater than for GI or dermal symptoms (4.9, 1.2 and 1.2 weeks, respectively, p<0.001), with an average number of GP visits per person per year being twice as frequent (0.48, 0.26, 0.19 respectively, p<0.001). However, on a per episode basis, a higher proportion of people saw a GP or were hospitalised for GI symptoms.

Conclusions
This first comparative study of three different symptom complexes showed that although respiratory symptoms are most common, GI symptoms cause a greater per episode burden on healthcare resources. Measuring and comparing the community based burden of these symptom complexes will assist evidence-based allocation of resources.
Impact of 5-HT3 receptor antagonists on chemotherapy-induced nausea and vomiting: a retrospective cohort study
Authors: Lin Swu-Jane , Hatoum Hind T , Buchner Deborah , Cox David , Balu Sanjeev 
Published: July 2012

Abstract

Background
1st generation 5-hydroxytryptamine receptor antagonists (5-HT3 RAs), and palonosetron, a 2nd generation 5-HT3 RA, are indicated for the prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) associated with moderately (MEC) and highly emetogenic CT agents (HEC). This study explores the impact of step therapy policies requiring use of an older 5-HT3 RA before palonosetron on risk of CINV associated with hospital or emergency department (ED) admissions.

Methods
Patients who received cyclophosphamide post breast cancer (BC) surgery or who were diagnosed with lung cancer on carboplatin (LC-carboplatin) or cisplatin (LC-cisplatin) were selected from PharMetrics’ (IMS LifeLink) claims dataset (2005-2008). Patients were followed for 6 months from initial CT administration for CINV events identified through ICD-9-CM codes. Patients were grouped into those initiated with older, generic 5-HT3 RAs (ondansetron, granisetron, and dolasetron) and those initiated and maintained on palonosetron throughout study follow-up. CINV events and CINV days were analyzed using multivariate regressions controlling for demographic and clinical variables.

Results
Eligible patients numbered 3,606 in BC, 4,497 in LC-carboplatin and 1,154 in LC-cisplatin cohorts, with 52%, 40%, and 34% in the palonosetron group, respectively. There was no significant difference between the two 5-HT3 RA groups in age or Charlson Comorbidity Index among the two MEC cohorts (BC and LC-carboplatin). Among the LC-cisplatin cohort, palonosetron users were older with more males than the older 5-HT3 RA group (age: 60.1 vs. 61.3; males, 66.9% vs. 56.9%). Compared to the older 5-HT3 RAs, the palonosetron groups incurred 22%-51% fewer 5-HT3 RA pharmacy claims, had fewer patients with CINV events (3.5% vs. 5.5% in BC, 9.5% vs. 12.8% in LC-carboplatin, 16.4% vs. 21.7% in LC-cisplatin), and had lower risk for CINV events (odds ratios 0.62, 0.71, or 0.71, respectively; p < 0.05). The BC and LC-carboplatin palonosetron groups experienced 50% and 30% fewer CINV days than the generic 5-HT3 RA group (p < 0.05).

Conclusions
Patients with breast or lung cancer initiated and maintained on palonosetron were at significantly lower risk for potentially costly CINV versus those on older 5-HT3 RAs. Further studies on impact of step therapy policy are warranted in order to minimize the clinical and economic burden of CINV.
Open-label trial with artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria three years after its broad introduction in Jimma Zone, Ethiopia
Authors: Eshetu Teferi , Abdo Nasir , Bedru Kunuz H , Fekadu Sintayehu , Wieser Andreas , Pritsch Michael , Löscher Thomas , Berens-Riha Nicole 
Published: July 2012

Abstract

Background
In Jimma Zone, Ethiopia, the first-line treatment of uncomplicated falciparum malaria has been changed from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (AL) in 2006. The objective of this study was to assess the effectiveness of AL in Jimma Zone two to three years after its broad introduction.

Methods
An open-label, single-arm, 42-day study of AL against falciparum malaria was conducted in four areas with moderate transmission in Jimma Zone between November 2008 and January 2009 and between August and December 2009. Patients (one-81 years) with uncomplicated Plasmodium falciparum mono-infection were consecutively enrolled. Follow-up visits were at day 2, 3, 7, 28 and 42 or any other day if symptoms reoccurred. Primary and secondary endpoints were PCR-corrected and uncorrected cure rates (molecular differentiation between recrudescence and re-infection) on days 28 and 42. Other secondary endpoints were gametocytaemia at day 7 and day 28, parasitaemia at day 2 and 3, and re-infection rates at day 28 and day 42.

Results
Of 348 enrolled patients, 313 and 301 completed follow-up at day 28 and at day 42, respectively. No early treatment failure occurred. For per protocol analysis, PCR-uncorrected cure rates at day 28 and 42 were 99.1% (95% CI 98.0-100.0) and 91.1% (95% CI 87.9-94.3), respectively. PCR-corrected cure rates at day 28 and 42 were 99.4% (95% CI 98.5-100.0) and 94.7% (95% CI 92.2-97.2), respectively. PCR-corrected cure rate at day 42 for children ≤5 years was 90.6% (95% CI 82.4-98.7) only. Adverse events were in general mild to moderate. Incidence of new infections was 3.4% during 42 days, no new infections with Plasmodium vivax were observed. Microscopically detected gametocytaemia was reduced by 80% between day 0 and day 7.

Conclusion
In general, AL was effective and well tolerated in Jimma Zone, Ethiopia. However, the PCR-corrected recrudescence rate per-protocol at day 42 for children ≤5 years was 9.4%. Therefore, further development should be monitored on a regular basis as recommended by WHO.
Sex differences in the response of the alveolar macrophage proteome to treatment with exogenous surfactant protein-A
Authors: Phelps David S , Umstead Todd M , Floros Joanna 
Published: July 2012

AbstractBackgroundMale wild type (WT) C57BL/6 mice are less capable of clearing bacteria and surviving from bacterial pneumonia than females. However, if an oxidative stress (acute ozone exposure) occurs before infection, the advantage shifts to males who then survive at higher rates than females. We have previously demonstrated that survival in surfactant protein-A (SP-A) knockout (KO) mice compared to WT was significantly reduced. Because the alveolar macrophage (AM) is pivotal in host defense we hypothesized that SP-A and circulating sex hormones are responsible for these sex differences. We used 2D-DIGE to examine the relationship of sex and SP-A on the AM proteome. The role of SP-A was investigated by treating SP-A KO mice with exogenous SP-A for 6 and 18 hr and studying its effects on the AM proteome.ResultsWe found: 1) less variance between KO males and females than between the WT counterparts by principal component analysis, indicating that SP-A plays a role in sex differences; 2) fewer changes in females when the total numbers of significantly changing protein spots or identified whole proteins in WT or 18 hr SP-A-treated males or females were compared to their respective KO groups; 3) more proteins with functions related to chaperones or protease balance and Nrf2-regulated proteins changed in response to SP-A in females than in males; and 4) the overall pattern of SP-A induced changes in actin-related proteins were similar in both sexes, although males had more significant changes.ConclusionsAlthough there seems to be an interaction between sex and the effect of SP-A, it is unclear what the responsible mechanisms are. However, we found that several of the proteins that were expressed at significantly higher levels in females than in males in WT and/or in KO mice are known to interact with the estrogen receptor and may thus play a role in the SP-A/sex interaction. These include major vault protein, chaperonin subunit 2 (beta) (CCT2), and Rho GDP alpha dissociation inhibitor. We conclude that sex differences exist in the proteome of AM derived from male and female mice and that SP-A contributes to these sex differences.