bluuebunny/crossref_metadata_2025_split huggingface dataset:
SCN5Aallelic expression imbalance in African-Americans heterozygous for the common variant p.Ser1103Tyr
Authors: Killen Stacy AS , Kunic Jennifer , Wang Lily , Lewis Adele , Levy Bruce P , Ackerman Michael J , George Alfred L 
Published: May 2010

Abstract

Background
Heterozygous and homozygous carriers of SCN5A-p.Ser1103Tyr, a common genetic variant with functional effects among African-Americans, have an increased risk of sudden death. We hypothesized that some heterozygous carriers may have unequal expression of wild-type and variant alleles and secondarily that predominance of the variant gene copy could further increase risk for sudden death in this population.

Methods
We quantified allele-specific expression of SCN5A-p.Ser1103Tyr by real-time reverse-transcription polymerase chain reaction (RT-PCR) in heart tissue from heterozygous African-American infants, who died from sudden infant death syndrome (SIDS) or from other causes, to test for allelic expression imbalance.

Results
We observed significant allelic expression imbalance in 13 of 26 (50%) African-American infant hearts heterozygous for SCN5A-p.Ser1103Tyr, and a significant (p < 0.0001) bimodal distribution of log2 allelic expression ratios. However, there were no significant differences in the mean log2 allelic expression ratios in hearts of infants dying from SIDS as compared to infants dying from other causes and no significant difference in the proportion of cases with greater expression of the variant allele.

Conclusions
Our data provide evidence that SCN5A allelic expression imbalance occurs in African-Americans heterozygous for p.Ser1103Tyr, but this phenomenon alone does not appear to be a marker for risk of SIDS.
How does the New Cooperative Medical Scheme influence health service utilization? A study in two provinces in rural China
Authors: Yu Baorong , Meng Qingyue , Collins Charles , Tolhurst Rachel , Tang Shenglan , Yan Fei , Bogg Lennart , Liu Xiaoyun 
Published: May 2010

Abstract

Background
Many countries are developing health financing mechanisms to pursue the goal of universal coverage. In China, a rural health insurance system entitled New Cooperative Medical Scheme (NCMS) is being developed since 2003. Although there is concern about whether the NCMS will influence the serious situation of inequity in health service utilization in rural China, there is only limited evidence available. This paper aims to assess the utilisation of outpatient and inpatient services among different income groups and provinces under NCMS in rural China.

Methods
Using multistage sampling processes, a cross-sectional household survey including 6,147 rural households and 22,636 individuals, was conducted in six counties in Shandong and Ningxia Provinces, China. Chi-square test, Poisson regression and log-linear regression were applied to analyze the association between NCMS and the utilization of outpatient and inpatient services and the length of stay for inpatients. Qualitative methods including individual interview and focus group discussion were applied to explain and complement the findings from the household survey.

Results
NCMS coverage was 95.9% in Shandong and 88.0% in Ningxia in 2006. NCMS membership had no significant association with outpatient service utilization regardless of income level and location.
Inpatient service utilization has increased for the high income group under NCMS, but for the middle and low income, the change was not significant. Compared with non-members, NCMS members from Ningxia used inpatient services more frequently, while members from Shandong had a longer stay in hospital.
High medical expenditure, low reimbursement rate and difference in NCMS policy design between regions were identified as the main reasons for the differences in health service utilization.

Conclusions
Outpatient service utilization has not significantly changed under NCMS. Although utilization of inpatient service in general has increased under NCMS, people with high income tend to benefit more than the low income group. While providing financial protection against catastrophic medical expenditure is the principal focus of NCMS, this study recommends that outpatient services should be incorporated in future NCMS policy development. NCMS policy should also be more equity oriented to achieve its policy goal.
Study protocol: national research partnership to improve primary health care performance and outcomes for Indigenous peoples
Authors: Bailie Ross , Si Damin , Shannon Cindy , Semmens James , Rowley Kevin , Scrimgeour David J , Nagel Tricia , Anderson Ian , Connors Christine , Weeramanthri Tarun , Thompson Sandra , McDermott Robyn , Burke Hugh , Moore Elizabeth , Leon Dallas , Weston Richard , Grogan Haylene , Stanley Andrew , Gardner Karen 
Published: May 2010

Abstract

Background
Strengthening primary health care is critical to reducing health inequity between Indigenous and non-Indigenous Australians. The Audit and Best practice for Chronic Disease Extension (ABCDE) project has facilitated the implementation of modern Continuous Quality Improvement (CQI) approaches in Indigenous community health care centres across Australia. The project demonstrated improvements in health centre systems, delivery of primary care services and in patient intermediate outcomes. It has also highlighted substantial variation in quality of care. Through a partnership between academic researchers, service providers and policy makers, we are now implementing a study which aims to 1) explore the factors associated with variation in clinical performance; 2) examine specific strategies that have been effective in improving primary care clinical performance; and 3) work with health service staff, management and policy makers to enhance the effective implementation of successful strategies.

Methods/Design
The study will be conducted in Indigenous community health centres from at least six States/Territories (Northern Territory, Western Australia, New South Wales, South Australia, Queensland and Victoria) over a five year period. A research hub will be established in each region to support collection and reporting of quantitative and qualitative clinical and health centre system performance data, to investigate factors affecting variation in quality of care and to facilitate effective translation of research evidence into policy and practice. The project is supported by a web-based information system, providing automated analysis and reporting of clinical care performance to health centre staff and management.

Discussion
By linking researchers directly to users of research (service providers, managers and policy makers), the partnership is well placed to generate new knowledge on effective strategies for improving the quality of primary health care and fostering effective and efficient exchange and use of data and information among service providers and policy makers to achieve evidence-based resource allocation, service planning, system development, and improvements of service delivery and Indigenous health outcomes.
NOTCH2 in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without TP53 mutations
Authors: Fu Yi-Ping , Edvardsen Hege , Kaushiva Alpana , Arhancet Juan P , Howe Tiffany M , Kohaar Indu , Porter-Gill Patricia , Shah Anushi , Landmark-Høyvik Hege , Fosså Sophie D , Ambs Stefan , Naume Bjørn , Børresen-Dale Anne-Lise , Kristensen Vessela N , Prokunina-Olsson Ludmila 
Published: May 2010

Abstract

Background
A recent genome-wide association study (GWAS) has identified a single nucleotide polymorphism (SNP) rs11249433 in the 1p11.2 region as a novel genetic risk factor for breast cancer, and this association was stronger in patients with estrogen receptor (ER)+ versus ER- cancer.

Results
We found association between SNP rs11249433 and expression of the NOTCH2 gene located in the 1p11.2 region. Examined in 180 breast tumors, the expression of NOTCH2 was found to be lowest in tumors with TP53 mutations and highest in TP53 wild-type/ER+ tumors (p = 0.0059). In the latter group, the NOTCH2 expression was particularly increased in carriers of the risk genotypes (AG/GG) of rs11249433 when compared to the non-risk AA genotype (p = 0.0062). Similar association between NOTCH2 expression and rs11249433 was observed in 60 samples of purified monocytes from healthy controls (p = 0.015), but not in total blood samples from 302 breast cancer patients and 76 normal breast tissue samples. We also identified the first possible dominant-negative form of NOTCH2, a truncated version of NOTCH2 consisting of only the extracellular domain.

Conclusion
This is the first study to show that the expression of NOTCH2 differs in subgroups of breast tumors and by genotypes of the breast cancer-associated SNP rs11249433. The NOTCH pathway has key functions in stem cell differentiation of ER+ luminal cells in the breast. Therefore, increased expression of NOTCH2 in carriers of rs11249433 may promote development of ER+ luminal tumors. Further studies are needed to investigate possible mechanisms of regulation of NOTCH2 expression by rs11249433 and the role of NOTCH2 splicing forms in breast cancer development.
Anti-obesity effect of an isoflavone fatty acid ester on obese mice induced by high fat diet and its potential mechanism
Authors: Yao Yao , Li Xiao-Bo , Zhao Wei , Zeng Yan-Yan , Shen Hong , Xiang Hua , Xiao Hong 
Published: May 2010

Abstract

Background
The novel compound 1a is one of the isoflavone fatty acid esters. In order to investigate the anti-obesity effect of compound 1a and its potential mechanism of influence in adipocyte differentiation, Obese male C57BL/6J mice induced by high-fat diet (HFD) and rat preadipocytes (3T3-L1 cell) were used.

Methods
After 4-week HFD induction, the obese model was made successfully. After treatment with compound 1a, mice plasma biochemistry parameters were analyzed. In addition, mice hepatic tissue slice was observed. In in vitro research, 3T3-L1 cell differentiation by Oil-Red-O staining and adipocyte apoptosis was detected by flow cytometry.

Results
The in vivo results implied that compound 1a significantly decreased the body weight, white adipose tissue weight of obesity mice(p < 0.05), reduced leptin and TG in plasma(p < 0.05), elevated HDL-C in serum(p < 0.05). The in vitro results suggested that compound 1a could significantly suppress the adipocyte viability and lipid accumulation in the differentiation of preadipocyte, and induce apoptosis in both preadipocytes and mature adipocytes(p < 0.05).

Conclusion
Compound 1a regulates serum lipid profiles, decreases adipose tissue mass and body weight gain by inducing adipocyte apoptosis in high fat diet induced mice. Thus, it may be used to treat obese patients with hypercholesterolemia and hypertriglyceridemia.
Effective inhibition of HCMV UL49 gene expression and viral replication by oligonucleotide external guide sequences and RNase P
Authors: Zhang WenJun , Li HongJian , Li YueQin , Zeng ZhiFeng , Li ShiQian , Zhang Xin , Zou Yi , Zhou TianHong 
Published: May 2010

Abstract

Background
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that typically causes asymptomatic infections in healthy individuals but may lead to serious complications in newborns and immunodeficient individuals. The emergence of drug-resistant strains of HCMV has posed a need for the development of new drugs and treatment strategies. Antisense molecules are promising gene-targeting agents for specific regulation of gene expression. External guide sequences (EGSs) are oligonucleotides that consist of a sequence complementary to a target mRNA and recruit intracellular RNase P for specific degradation of the target RNA. The UL49-deletion BAC of HCMV was significantly defective in growth in human foreskin fibroblasts. Therefore, UL49 gene may serve as a potential target for novel drug development to combat HCMV infection. In this study, DNA-based EGS molecules were synthesized to target the UL49 mRNA of human cytomegalovirus (HCMV).

Results
By cleavage activity assessing in vitro, the EGS aimed to the cleavage site 324 nt downstream from the translational initiation codon of UL49 mRNA (i.e. EGS324) was confirmed be efficient to direct human RNase P to cleave the target mRNA sequence. When EGS324 was exogenously administered into HCMV-infected human foreskin fibroblasts (HFFs), a significant reduction of ~76% in the mRNA and ~80% in the protein expression of UL49 gene, comparing with the cells transfected with control EGSs. Furthermore, a reduction of about 330-fold in HCMV growth were observed in HCMV-infected HFFs treated with the EGS.

Conclusions
These results indicated that UL49 gene was essential for replication of HCMV. Moreover, our study provides evidence that exogenous administration of a DNA-based EGS can be used as a potential therapeutic approach for inhibiting gene expression and replication of a human virus.
Vascular injuries following road traffic collisions in a high-income developing country: a prospective cohort study
Authors: Jawas Ali , Hammad Fayez , Eid Hani O , Abu-Zidan Fikri M 
Published: May 2010

AbstractBackgroundThe mechanism and pattern of vascular injury vary between different populations. The commonest mechanism of vascular injury in civilian practice is road traffic collisions. We aimed to prospectively study the incidence, detailed mechanism and anatomical distribution of hospitalized vascular trauma patients following road traffic collisions in a high-income developing country.MethodsData were collected prospectively on road traffic collision injuries in the whole city of Al-Ain, United Arab Emirates, from April 2006 to October 2007 with full details of mechanism of injury and its relation to sustained injuries.ResultsOut of 1008 patients in the registry, 13 patients had vascular injury, a calculated incidence of 1.87 cases/100 000 inhabitants per year. There were eight car occupants, four pedestrians, and one motorcyclist. Upper limb vascular injuries were the most common anatomical site (n = 4) followed by thoracic aorta (n = 3). All thoracic aortic injuries were acceleration injuries (pedestrians hit by a moving vehicle). None of the eight car occupants was wearing a seatbelt and the majority sustained a front impact deceleration injuries. The median injury severity score, hospital stay, and ICU stay were significantly higher in the vascular injury group compared with nonvascular group (P < 0.0001). Three patients died (23%); two due to severe liver trauma and one due to rupture thoracic aorta.ConclusionsThe incidence of hospitalized vascular injury due to road traffic collisions in Al-Ain city is 1.87 cases/100 000 inhabitants. These injuries occurred mainly in the upper part of the body. Seatbelt compliance of car occupants having vascular injuries was very low. Compliance with safety measures needs more enforcement in our community.
A rapid method for the generation of uniform acellular bone explants: a technical note
Authors: Jähn Katharina , Braunstein Volker , Furlong Pamela I , Simpson Angharad E , Richards R Geoff , Stoddart Martin J 
Published: May 2010

Abstract

Background
Bone graft studies lack standardized controls. We aim to present a quick and reliable method for the intra-operative generation of acellular bone explants.

Methods
Therefore, ovine cancellous bone explants from the iliac crest were prepared and used to test several methods for the induction of cell death. Over night heat inactivation was used as positive treatment control, methods to be investigated included UV light, or X- ray exposure, incubation in a hypotonic solution (salt-free water) and a short cycle of repeated freezing and thawing.

Results
Viability of treated and 2 days cultured bone explants was investigated by lactate dehydrogenase assay. Non-treated cultured control explants maintained around 50% osteocyte viability, while osteocyte survival after the positive treatment control was abolished. The most dramatic loss in cell viability, together with a low standard deviation, was a repeated cycle of freezing and thawing.

Conclusions
To summarize, we present a freeze-thaw method for the creation of acellular bone explants, which is easy to perform, not time-consuming and provides consistent results.
Effects of IL-6 and AG490 on regulation of Stat3 signaling pathway and invasion of human pancreatic cancer cells in vitro
Authors: Huang Chen , Yang Guang , Jiang Tao , Huang Kejian , Cao Jun , Qiu Zhengjun 
Published: May 2010

Abstract

Background
Signal transducer and activator of transcription 3 (Stat3) is a member of the Janus-activated kinase(Jak)/Stat signaling pathway. Abnormal activation of Stat3 plays a critical role in metastasis and invasion in varieties of human tumors including pancreatic cancer. This study aimed to investigate the mechanisms of activation and blocking of the Stat3 signaling pathway and its effects on invasion and metastasis of human pancreatic cancer cells.

Methods
The Jak inhibitor AG490 and interleukin-6 (IL-6) were added to the culture media of human pancreatic cancer cells SW1990 and Capan-2, respectively. Cell growth was measured by MTT assays. Western blotting and immunocytochemistry were performed to detect phosphorylated Stat3 (p-Stat3) protein, while VEGF and MMP-2 mRNA and protein expression were examined with fluorescence quantitative polymerase chain reaction and Western blotting, respectively. The invasion ability of SW1990 and Capan-2 cells was determined by cell invasion assay.

Results
Stat3 was activated by IL-6 in Capan-2 cells; protein expression of p-Stat3 was increased significantly in Capan-2 cells. IL-6 remarkably promoted the growth of Capan-2 cells (P < 0.05), and VEGF and MMP-2 mRNA and protein expression were increased significantly. Also, IL-6 increased the invasion ability of Capan-2 cells. AG490 inhibited Stat3 activation in SW1990 cells. Western blotting and immunocytochemistry analysis showed that p-Stat3 protein expression was decreased significantly with AG490 treatment in SW1990 cells. AG490 remarkably inhibited the growth of Capan-2 cells (P < 0.05), and VEGF and MMP-2 mRNA and protein expression was decreased significantly. And AG490 decreased the invasion ability of SW1990 cells.

Conclusions
Abnormal activation of Stat3 plays an important role in the invasion and metastasis of pancreatic cancer. Activation and blocking of the Stat3 signaling pathway can affect invasion ability and expression of the VEGF and MMP-2 genes in pancreatic cancer cells. The Stat3 signaling pathway may provide a novel therapeutic target for treatment of pancreatic cancer.
The association between leptin, interleukin-6, and hip radiographic osteoarthritis in older people: a cross-sectional study
Authors: Stannus Oliver P , Jones Graeme , Quinn Stephen J , Cicuttini Flavia M , Dore Dawn , Ding Changhai 
Published: May 2010

Abstract
Introduction
The associations between leptin, interleukin (IL)-6, and hip radiographic osteoarthritis (OA) have not been reported, and their roles in obesity-related hip OA are unclear. The aim of this study was to describe the associations between leptin, IL-6, and hip radiographic osteoarthritis (ROA) in older adults.

Methods
A cross-sectional sample of 193 randomly selected subjects (mean age, 63 years; range, 52 to 78 years; 48% female subjects) were studied. Hip ROA, including joint-space narrowing (JSN) and osteophytes, was determined by anteroposterior radiograph. Serum levels of leptin and interleukin (IL)-6 were measured with radioimmunoassay. Fat mass was measured with dual-energy x-ray absorptiometry (DXA). Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated.

Results
In multivariable analysis, hip JSN was associated with serum levels of leptin in the whole sample (β = 0.046 per μg/L, P = 0.024 for superior; β = 0.068 per μg/L, P = 0.004 for axial compartment) and IL-6 only in females (β = 0.241 per pg/ml, P = 0.002 for superior; β = 0.239 per pg/ml, P = 0.001 for axial compartment). The positive associations between body-composition measures (BMI, WHR, percentage total fat mass, and percentage trunk fat mass) and hip JSN in women became nonsignificant after adjustment for leptin but not for IL-6. No significant associations were found between leptin, IL-6, and the presence or severity of osteophytes.

Conclusions
This study suggests that metabolic and inflammatory mechanisms may play a role in the etiology of hip OA and that the associations between body composition and hip JSN are mediated by leptin, particularly in women.
Differential down-regulation of HLA-DR on monocyte subpopulations during systemic inflammation
Authors: Kim Oh Yoen , Monsel Antoine , Bertrand Michèle , Coriat Pierre , Cavaillon Jean-Marc , Adib-Conquy Minou 
Published: May 2010

Abstract
Introduction
Decreased expression of human leukocyte antigen class II (HLA-DR) on monocytes is a hallmark of altered immune status in patients with a systemic inflammatory response syndrome (SIRS). So far, the analyses were mainly performed without taking into account monocytes subpopulations.

Methods
We studied this modification on CD14HIGH and CD14LOW monocytes of 20 SIRS patients undergoing abdominal aortic surgery (AAS), 20 patients undergoing carotid artery surgery (CAS), and 9 healthy controls, and we investigated mediators and intracellular molecules that may be involved in this process.

Results
HLA-DR on CD14HIGH monocytes started to decrease during surgery, after blood reperfusion, and was further reduced post-surgery. In contrast, HLA-DR expression on CD14LOW cells only decreased after surgery, and to a lesser extent than on CD14HIGH monocytes. Negative correlations were found between the reduction of HLA-DR expression and the change in cortisol levels for both subpopulations, whereas a negative correlation between interleukin-10 (IL-10) levels and HLA-DR modulation was only observed for CD14HIGH cells. In accordance with these ex vivo results, HLA-DR on CD14HIGH and CD14LOW monocytes of healthy donors was reduced following incubation with hydrocortisone, whereas IL-10 only acted on CD14HIGH subpopulation. Furthermore, flow cytometry revealed that the expression of IL-10 receptor was higher on CD14HIGH versus CD14LOW monocytes. In addition, hydrocortisone, and to a lesser extent IL-10, reversed the up-regulation of HLA-DR induced by bacterial products. Finally, membrane-associated RING-CH-1 protein (MARCH1) mRNA, a negative regulator of MHC class II, was up-regulated in monocytes of AAS patients on Day 1 post-surgery, and in those of healthy subjects exposed to hydrocortisone.

Conclusions
This study reveals that HLA-DR expression is modulated differently on CD14HIGH (classical) versus CD14LOW (inflammatory) monocytes after systemic inflammation.