bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of an osteoporosis self-assessment tool to identify primary osteoporosis and new osteoporotic vertebral fractures in postmenopausal Chinese women in Beijing
Authors: Yang Yong , Wang BingQiang , Fei Qi , Meng Qian , Li Dong , Tang Hai , Li JinJun , Su Nan
Published: September 2013

Background

This study aimed to validate the effectiveness of the Osteoporosis Self-assessment Tool for Asians (OSTA) in identifying postmenopausal women at increased risk of primary osteoporosis and painful new osteoporotic vertebral fractures in a large selected Han Chinese population in Beijing.

Methods

We assessed the performance of the OSTA in 1201 women. Subjects with an OSTA index > -1 were classified as the low risk group, and those with an index ≤ -1 were classified as the increased risk group. Osteoporosis is defined by a T-score ≤ 2.5 standard deviations according to the WHO criteria. All painful, new vertebral fractures were identified by X-ray and MRI scans with correlating clinical signs and symptoms. We determined the sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve for correctly selecting women with osteoporosis and painful new vertebral fractures.

Results

Of the study subjects, 29.3% had osteoporosis, and the prevalence of osteoporosis increased progressively with age. The areas under the ROC curves of the OSTA index (cutoff = -1) to identify osteoporosis in the femoral neck, total hip, and lumbar spine were 0.824, 0.824, and 0.776, respectively. The sensitivity and specificity of the OSTA index (cutoff = -1) to identify osteoporosis in healthy women were 66% and 76%, respectively. With regard to painful new vertebral fractures, the area under the ROC curve relating the OSTA index (cutoff = -1) to new vertebral fractures was 0.812.

Conclusions

The OSTA may be a simple and effective tool for identifying the risk of osteoporosis and new painful osteoporotic vertebral fractures in Han Chinese women.
Infected forearm nonunion treated by bone transport after debridement
Authors: Liu Tang , Liu Zhenyang , Ling Lin , Zhang Xiangsheng
Published: September 2013

Background

This is a therapeutic study to evaluate the results of the management of forearm infected nonunion using bone transport with external fixators after debridement.

Methods

We have retrospectively reviewed a consecutive series of 21 patients from October 1994 to June 2010 in our institution who were treated for the forearm infected nonunion by bone transport with external fixator after debridement. There were 12 males and 9 females. The mean age of the patients was 27.1 years. Of the initial fractures, nonunion of the radius alone invovled in 7 patients, nonunion of the ulna alone invovled in 12, and nonunion of the radius and ulna invovled in 2. Nineteen limbs (85.7%) were in active infected state with sinus and drainage. The mean amount of bone defect was 3.1 cm (range 1.8-4.6 cm) as measured on plain radiographs.

Results

The mean follow-up was 77.5 months. All patients achieved bony union and were satisfied with the functional and cosmetic outcome. All the infection had been controlled. The mean external fixation index was 42.5 day/cm. The average time for wound healing was 42 days. The mean length gained was 3.5 cm (2.1-5.3 cm).

Conclusions

The technique of bone transport after debridement is a safe, effective, and minimally invasive treatment for forearm infected nonunion.
Detection of persistent organic pollutants binding modes with androgen receptor ligand binding domain by docking and molecular dynamics
Authors: Xu Xian Jin , Su Ji Guo , Bizzarri Anna Rita , Cannistraro Salvatore , Liu Ming , Zeng Yi , Chen Wei Zu , Wang Cun Xin
Published: September 2013

Background

Persistent organic pollutants (POPs) are persistent in the environment after release from industrial compounds, combustion productions or pesticides. The exposure of POPs has been related to various reproductive disturbances, such as reduced semen quality, testicular cancer, and imbalanced sex ratio. Among POPs, dichlorodiphenyldichloroethylene (4,4’-DDE) and polychlorinated biphenyls (PCBs) are the most widespread and well-studied compounds. Recent studies have revealed that 4,4’-DDE is an antagonist of androgen receptor (AR). However, the mechanism of the inhibition remains elusive. CB-153 is the most common congener of PCBs, while the action of CB-153 on AR is still under debate.

Results

Molecular docking and molecular dynamics (MD) approaches have been employed to study binding modes and inhibition mechanism of 4,4’-DDE and CB-153 against AR ligand binding domain (LBD). Several potential binding sites have been detected and analyzed. One possible binding site is the same binding site of AR natural ligand androgen 5α-dihydrotestosterone (DHT). Another one is on the ligand-dependent transcriptional activation function (AF2) region, which is crucial for the co-activators recruitment. Besides, a novel possible binding site was observed for POPs with low binding free energy with the receptor. Detailed interactions between ligands and the receptor have been represented. The disrupting mechanism of POPs against AR has also been discussed.

Conclusions

POPs disrupt the function of AR through binding to three possible biding sites on AR/LBD. One of them shares the same binding site of natural ligand of AR. Another one is on AF2 region. The third one is in a cleft near N-terminal of the receptor. Significantly, values of binding free energy of POPs with AR/LBD are comparable to that of natural ligand androgen DHT.
A Socio-technical assessment of the success of picture archiving and communication systems: the radiology technologist’s perspective
Authors: Tzeng Wen-Sheng , Kuo Kuang-Ming , Lin Huang-Wei , Chen Tai-Yuan
Published: September 2013

Background

With the increasing prevalence of Picture Archiving and Communication Systems (PACS) in healthcare institutions, there is a growing need to measure their success. However, there is a lack of published literature emphasizing the technical and social factors underlying a successful PACS.

Methods

An updated Information Systems Success Model was utilized by radiology technologists (RTs) to evaluate the success of PACS at a large medical center in Taiwan. A survey, consisting of 109 questionnaires, was analyzed by Structural Equation Modeling.

Results

Socio-technical factors (including system quality, information quality, service quality, perceived usefulness, user satisfaction, and PACS dependence) were proven to be effective measures of PACS success. Although the relationship between service quality and perceived usefulness was not significant, other proposed relationships amongst the six measurement parameters of success were all confirmed.

Conclusions

Managers have an obligation to improve the attributes of PACS. At the onset of its deployment, RTs will have formed their own subjective opinions with regards to its quality (system quality, information quality, and service quality). As these personal concepts are either refuted or reinforced based on personal experiences, RTs will become either satisfied or dissatisfied with PACS, based on their perception of its usefulness or lack of usefulness. A satisfied RT may play a pivotal role in the implementation of PACS in the future.
Surface display of recombinant proteins on Escherichia coli by BclA exosporium of Bacillus anthracis
Authors: Park Tae Jung , Heo Nam Su , Yim Sung Sun , Park Jong Hyun , Jeong Ki Jun , Lee Sang Yup
Published: September 2013

Background

The anchoring motif is one of the most important aspects of cell surface display as well as efficient and stable display of target proteins. Thus, there is currently a need for the identification and isolation of novel anchoring motifs.

Results

A system for the display of recombinant proteins on the surface of Escherichia coli was developed using the Bacillus anthracis exosporal protein (BclA) as a new anchoring motif. For the surface display of recombinant proteins, the BAN display platform was constructed in which a target protein is linked to the C-terminus of N-terminal domain (21 amino acids) of BclA. The potential application of BAN platform for cell surface display was demonstrated with two model proteins of different size, the Bacillus sp. endoxylanase (XynA) and monooxygenase (P450 BM3m2). Through experimental analysis including outer membrane fractionation, confocal microscopy and activity assay, it was clearly confirmed that both model proteins were successfully displayed with high activities on the E. coli cell surface.

Conclusions

These results of this study suggest that the strategy employing the B. anthracis BclA as an anchoring motif is suitable for the display of heterologous proteins on the surface of E. coli and consequently for various biocatalytic applications as well as protein engineering.
Expression profiling of ion channel genes predicts clinical outcome in breast cancer
Authors: Ko Jae-Hong , Ko Eun A , Gu Wanjun , Lim Inja , Bang Hyoweon , Zhou Tong
Published: September 2013

Background

Ion channels play a critical role in a wide variety of biological processes, including the development of human cancer. However, the overall impact of ion channels on tumorigenicity in breast cancer remains controversial.

Methods

We conduct microarray meta-analysis on 280 ion channel genes. We identify candidate ion channels that are implicated in breast cancer based on gene expression profiling. We test the relationship between the expression of ion channel genes and p53 mutation status, ER status, and histological tumor grade in the discovery cohort. A molecular signature consisting of ion channel genes (IC30) is identified by Spearman’s rank correlation test conducted between tumor grade and gene expression. A risk scoring system is developed based on IC30. We test the prognostic power of IC30 in the discovery and seven validation cohorts by both Cox proportional hazard regression and log-rank test.

Results

22, 24, and 30 ion channel genes are found to be differentially expressed with a change in p53 mutation status, ER status, and tumor histological grade in the discovery cohort. We assign the 30 tumor grade associated ion channel genes as the IC30 gene signature. We find that IC30 risk score predicts clinical outcome (P < 0.05) in the discovery cohort and 6 out of 7 validation cohorts. Multivariate and univariate tests conducted in two validation cohorts indicate that IC30 is a robust prognostic biomarker, which is independent of standard clinical and pathological prognostic factors including patient age, lymph node status, tumor size, tumor grade, estrogen and progesterone receptor status, and p53 mutation status.

Conclusions

We identified a molecular gene signature IC30, which represents a promising diagnostic and prognostic biomarker in breast cancer. Our results indicate that information regarding the expression of ion channels in tumor pathology could provide new targets for therapy in human cancers.
Efficacy of combination of Ezetimibe 10 mg and rosuvastatin 2.5 mg versus rosuvastatin 5 mg monotherapy for hypercholesterolemia in patients with type 2 diabetes
Authors: Torimoto Keiichi , Okada Yosuke , Mori Hiroko , Hajime Maiko , Tanaka Kenichi , Kurozumi Akira , Narisawa Manabu , Yamamoto Sunao , Arao Tadashi , Matsuoka Hirofumi , Inokuchi Nobuo , Tanaka Yoshiya
Published: September 2013

Background

Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus, but many of these patients fail to achieve the target LDL-C level. Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin. However, in patients with type 2 diabetes who are already being treated with satins, it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose. Therefore, this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins.

Methods

The subjects were type 2 diabetic patients under treatment with rosuvastatin (2.5 mg daily), who had LDL-C levels ≥80 mg/dL. They were randomly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day (combination group, n = 40) or an increase of the rosuvastatin dose to 5 mg/day (dose escalation group, n = 39). These two groups were compared at baseline and after 12 weeks of treatment.

Results

The percent change of LDL-C was −31% in the combination group and −12% in the dose escalation group. Both groups showed a significant decrease, but the decrease was greater in the combination group. In both groups, there was a significant decrease in the levels of small dense LDL-C, oxidized LDL and remnant-like lipoprotein cholesterol. For all of these parameters, the percent changes were greater in the combination group. Only the combination group showed a significant decrease of triglycerides. Multivariate analysis was performed to identify factors associated with reaching an LDL-C level <80 mg/dL. As a result, add-on therapy with ezetimibe was extracted as a factor related to improvement of LDL-C.

Conclusions

Compared with increasing the dose of rosuvastatin, the combination of rosuvastatin and ezetimibe not only achieves quantitative but also qualitative improvement of serum lipid levels in type 2 diabetic patients, suggesting that this combination could suppress the progression of atherosclerosis.

Trial registration

UMIN000011005
Successful resection of hepatocellular cancer not amenable to Milan criteria and durable complete remission induced by systemic polichemotherapy after development of metastases – should we think about revising the current treatment guidelines in selected patients?
Authors: Rados Ivana , Badzek Sasa , Golem Hilda , Prejac Juraj , Gorsic Irma , Kekez Domina , Librenjak Niksa , Plestina Stjepko
Published: September 2013

Objectives

To refresh clinical diagnostic and therapeutic dilemmas in patients presenting with hepatocellular cancer (HCC) and to report a rare success of systemic polichemotherapy in metastatic HCC.

Methods

Case report of a patient with successfully resected HCC although initially deemed inoperable according to current guidelines, and who was successfully treated by systemic polichemotherapy after development of metastatic disease, resulting in a sustained complete remission.

Results

We describe a 71-year-old female with HCC initially treated by atypical liver resection, although not amenable to initial surgery according to current treatment guidelines, which resulted in 6 months disease-free interval. After development of pulmonary metastases, the patient was treated by systemic polichemotherapy, due to local unavailability of novel biologic agents. After 3 months of chemotherapy biochemical remission was confirmed, and after 10 months of active treatment complete radiological remission was verified according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, now exceeding 9 months in duration.

Conclusion

There is an increasing body of evidence that criteria for surgical interventions in HCC should be revised and expanded, and our case is an example of such an approach. Although novel biologic therapies are not widely available in all regions of the world due to their cost, currently there are no hard recommendations for use of chemotherapy in such areas. Since this is a large problem in clinical practice, we conclude that chemotherapy should be offered to selected patients of good performance status if novel agents are unavailable.
Removing financial barriers to access reproductive, maternal and newborn health services: the challenges and policy implications for human resources for health
Authors: McPake Barbara , Witter Sophie , Ensor Tim , Fustukian Suzanne , Newlands David , Martineau Tim , Chirwa Yotamu
Published: September 2013

Background

The last decade has seen widespread retreat from user fees with the intention to reduce financial constraints to users in accessing health care and in particular improving access to reproductive, maternal and newborn health services. This has had important benefits in reducing financial barriers to access in a number of settings. If the policies work as intended, service utilization rates increase. However this increases workloads for health staff and at the same time, the loss of user fee revenues can imply that health workers lose bonuses or allowances, or that it becomes more difficult to ensure uninterrupted supplies of health care inputs.

This research aimed to assess how policies reducing demand-side barriers to access to health care have affected service delivery with a particular focus on human resources for health.

Methods

We undertook case studies in five countries (Ghana, Nepal, Sierra Leone, Zambia and Zimbabwe). In each we reviewed financing and HRH policies, considered the impact financing policy change had made on health service utilization rates, analysed the distribution of health staff and their actual and potential workloads, and compared remuneration terms in the public sectors.

Results

We question a number of common assumptions about the financing and human resource inter-relationships. The impact of fee removal on utilization levels is mostly not sustained or supported by all the evidence. Shortages of human resources for health at the national level are not universal; maldistribution within countries is the greater problem. Low salaries are not universal; most of the countries pay health workers well by national benchmarks.

Conclusions

The interconnectedness between user fee policy and HRH situations proves difficult to assess. Many policies have been changing over the relevant period, some clearly and others possibly in response to problems identified associated with financing policy change. Other relevant variables have also changed.

However, as is now well-recognised in the user fee literature, co-ordination of health financing and human resource policies is essential. This appears less well recognised in the human resources literature. This coordination involves considering user charges, resource availability at health facility level, health worker pay, terms and conditions, and recruitment in tandem. All these policies need to be effectively monitored in their processes as well as outcomes, but sufficient data are not collected for this purpose.
Adaptive hierarchical modulation and power allocation for superposition-coded relaying
Authors: Yamaura Hirofumi , Kaneko Megumi , Hayashi Kazunori , Sakai Hideaki
Published: September 2013

We propose a relaying scheme based on superposition coding (SC) with discrete adaptive modulation and coding (AMC) for a three-node wireless relay system, based on half duplex transmission, where each node decodes messages by successive interference cancelation (SIC). Unlike the previous works where the transmission rate of each link is assumed to achieve Gaussian channel capacity, we design a practical superposition-coded relaying scheme with discrete AMC while taking into account the effect of decoding errors at each stage of the SIC process at each node. In our scheme, hierarchical modulation (HM) is used to create an SC message composed of one basic and one superposed message with optimized power allocation. We firstly introduce the proposed scheme without forward error correction (FEC) for high signal-to-noise ratio (SNR) region and provide the optimal power allocation between the superimposed messages. Next, we extend the uncoded scheme to incorporate FEC to overcome bad channel conditions. The power allocation in this case is based on an approximated expression of the bit error rate (BER). Numerical results show the performance gains of the proposed SC relaying scheme with HM compared to conventional schemes, over a large range of SNRs.
Suppression of experimental autoimmune encephalomyelitis by interleukin-10 transduced neural stem/progenitor cells
Authors: Klose Juliane , Schmidt Nils Ole , Melms Arthur , Dohi Makoto , Miyazaki Jun-ichi , Bischof Felix , Greve Bernhard
Published: September 2013

Neural stem/progenitor cells (NSPCs) have the ability to migrate into the central nervous system (CNS) to replace damaged cells. In inflammatory CNS disease, cytokine transduced neural stem cells may be used as vehicles to specifically reduce inflammation and promote cell replacement. In this study, we used NSPCs overexpressing IL-10, an immunomodulatory cytokine, in an animal model for CNS inflammation and multiple sclerosis (MS). Intravenous injection of IL-10 transduced neural stem/progenitor cells (NSPCIL-10) suppressed myelin oligodendrocyte glycoprotein aa 35–55 (MOG35-55)- induced experimental autoimmune encephalomyelitis (EAE) and, following intravenous injection, NSPCIL-10migrated to peripheral lymphoid organs and into the CNS. NSPCIL-10suppressed antigen-specific proliferation and proinflammatory cytokine production of lymph node cells obtained from MOG35-55 peptide immunized mice. In this model, IL-10 producing NSPCs act via a peripheral immunosuppressive effect to attenuate EAE.
Cross-protective immunity against influenza A/H1N1 virus challenge in mice immunized with recombinant vaccine expressing HA gene of influenza A/H5N1 virus
Authors: Yang Song , Niu Shumeng , Guo Zhihua , Yuan Ye , Xue Kun , Liu Sinan , Jin Hong
Published: September 2013

Background

Influenza virus undergoes constant antigenic evolution, and therefore influenza vaccines must be reformulated each year. Time is necessary to produce a vaccine that is antigenically matched to a pandemic strain. A goal of many research works is to produce universal vaccines that can induce protective immunity to influenza A viruses of various subtypes. Despite intensive studies, the precise mechanisms of heterosubtypic immunity (HSI) remain ambiguous.

Method

In this study, mice were vaccinated with recombinant virus vaccine (rL H5), in which the hemagglutinin (HA) gene of influenza A/H5N1 virus was inserted into the LaSota Newcastle disease virus (NDV) vaccine strain. Following a challenge with influenza A/H1N1 virus, survival rates and lung index of mice were observed. The antibodies to influenza virus were detected using hemagglutination inhibition (HI). The lung viral loads, lung cytokine levels and the percentages of both IFN-γ+CD4+and IFN-γ+CD8+T cells in spleen were detected using real-time RT-PCR, ELISA and flow cytometry respectively.

Results

In comparison with the group of mice given phosphate-buffered saline (PBS), the mice vaccinated with rL H5 showed reductions in lung index and viral replication in the lungs after a challenge with influenza A/H1N1 virus. The antibody titer in group 3 (H1N1-H1N1) was significantly higher than that in other groups which only low levels of antibody were detected. IFN-γ levels increased in both group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1). And the IFN-γ level of group 2 was significantly higher than that of group 1. The percentages of both IFN-γ+CD4+and IFN-γ+CD8+T cells in group 1(rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1) increased significantly, as measured by flow cytometry.

Conclusion

After the mice were vaccinated with rL H5, cross-protective immune response was induced, which was against heterosubtypic influenza A/H1N1 virus. To some extent, cross-protective immune response can be enhanced by IL-2 as an adjuvant. Cellular immune responses may play an important role in HSI against influenza virus.
Decreased antigenicity profiles of immune-escaped and drug-resistant hepatitis B surface antigen (HBsAg) double mutants
Authors: Zhang Mingshun , Ge Guohong , Yang Yonglin , Cai Xubing , Fu Qiang , Cai Jie , Huang Zuhu
Published: September 2013

Background

Selective pressure from either the immune response or the use of nucleoside analogs in antiviral therapy could be driving the emergence of HBV mutants. Because of the overlap of the open reading frame (ORF) S for the HBsAg and ORF P for viral polymerase, rtM204I and rtM204V mutations in the polymerase would produce sI195M and sW196S in the HBsAg. The combined effects of immune-escaped mutations (sT118M, sG145K, sG145R) and drug-resistant mutations (rtM204I, rtM204V) on the antigenicity profiles of HBsAg has not been widely explored.

Methods

To determine the combined effects of immune-escaped and drug-resistant mutants on the antigenicity profiles of HBsAg, recombinant plasmids encoding HBsAg double mutants were constructed using site-directed mutagenesis. The supernatant from each plasmid transfection was analyzed for HBsAg in the western-blotting and five of the most commonly used commercial ELISA kits in China.

Results

Western-blotting assay showed the successful expression of each HBsAg mutant. All five ELISA kits manifested similar avidity, which were demonstrated by the slope of the curves, for the sT118M mutant, and sT118M-rtM204I (sT118M-sI195M) and sT118M-rtM204V (sT118M-sW196S) double mutants, suggesting that drug-resistant YMDD mutants caused negligible losses in the antigenicity of immune-escaped sT118M HBsAg. In contrast, the presence of the rtM204I (sI195M) mutation, but not rtM204V (sW196S) in combination with the sG145K mutation significantly reduced the avidity of sG145K HBsAg. The rtM204I (sI195M) mutation also decreased the antigenicity profiles for sG145R HBsAg.

Conclusions

Drug-resistant mutations rtM204I (sI195M) and rtM204V (sW196S) caused significant reduction in antigenicity for the immune-escaped HBsAg mutants sG145K and sG145R, which may hamper HBV diagnosis and disease control from HBV blood-transfusion transmissions in China. The development of ELISA kits with a greater sensitivity for drug-resistant and immune-escaped HBsAg warrants further consideration.
Recognizing short coding sequences of prokaryotic genome using a novel iteratively adaptive sparse partial least squares algorithm
Authors: Chen Sun , Zhang Chun-ying , Song Kai
Published: September 2013

Background

Significant efforts have been made to address the problem of identifying short genes in prokaryotic genomes. However, most known methods are not effective in detecting short genes. Because of the limited information contained in short DNA sequences, it is very difficult to accurately distinguish between protein coding and non-coding sequences in prokaryotic genomes. We have developed a new Iteratively Adaptive Sparse Partial Least Squares (IASPLS) algorithm as the classifier to improve the accuracy of the identification process.

Results

For testing, we chose the short coding and non-coding sequences from seven prokaryotic organisms. We used seven feature sets (including GC content, Z-curve, etc.) of short genes.

In comparison with GeneMarkS, Metagene, Orphelia, and Heuristic Approachs methods, our model achieved the best prediction performance in identification of short prokaryotic genes. Even when we focused on the very short length group ([60–100 nt)), our model provided sensitivity as high as 83.44% and specificity as high as 92.8%. These values are two or three times higher than three of the other methods while Metagene fails to recognize genes in this length range.

The experiments also proved that the IASPLS can improve the identification accuracy in comparison with other widely used classifiers, i.e. Logistic, Random Forest (RF) and K nearest neighbors (KNN). The accuracy in using IASPLS was improved 5.90% or more in comparison with the other methods. In addition to the improvements in accuracy, IASPLS required ten times less computer time than using KNN or RF.

Conclusions

It is conclusive that our method is preferable for application as an automated method of short gene classification. Its linearity and easily optimized parameters make it practicable for predicting short genes of newly-sequenced or under-studied species.

Reviewers

This article was reviewed by Alexey Kondrashov, Rajeev Azad (nominated by Dr J.Peter Gogarten) and Yuriy Fofanov (nominated by Dr Janet Siefert).
Auricular acupuncture for prehypertension and stage 1 hypertension: study protocol for a pilot multicentre randomised controlled trial
Authors: Kim Joo-Hee , Jung Hyun Jung , Kim Tae-Hun , Lee Seunghoon , Kim Jung-Eun , Kang Kyung-Won , Jung So-Young , Kim Ae-Ran , Park Hyo-Ju , Shin Mi-Suk , Shin Kyung-Min , Jung Hee-Jung , Lee Seung-Deok , Hong Kwon-Eui , Choi Sun-Mi
Published: September 2013

Background

Hypertension, a worldwide public health problem, is a major risk factor for cardiovascular and kidney disease, and the medical and economic burden of hypertension is increasing. Auricular acupuncture has been used to treat various diseases, including hypertension. Several studies have shown that auricular acupuncture treatment decreases blood pressure in patients with hypertension; however, the scientific evidence is still insufficient. Therefore, we aimed to perform a randomised controlled clinical trial in patients with prehypertension and stage 1 hypertension to evaluate the effect and safety of auricular acupuncture.

Methods/designs

This on-going study is a two parallel arm, assessor-blinded, randomised controlled trial. Sixty participants with prehypertension and stage 1 hypertension will be recruited and randomly allocated into two groups in a 1:1 ratio. Participants in the auricular acupuncture group will receive auricular acupuncture treatment two times per week for 4 weeks. Participants in the usual care group will not receive any acupuncture treatment during the study period. All participants in both groups will be provided with verbal and written educational materials regarding the dietary and physical activity habits for controlling high blood pressure, and they will self-manage their lifestyle, including diet and exercise, during the study. The primary outcome is the 24-h average systolic and diastolic blood pressure, as measured with an ambulatory monitor. The secondary outcomes are the mean change in the average systolic and diastolic blood pressure during day- and night-time, the circadian rhythm of blood pressure, the mean arterial pressure, the change in blood pressure before and after auricular acupuncture treatment, the EuroQOL-5D (EQ-5D), heart rate variability (HRV), body mass index (BMI) and laboratory examination, including lipid profile and high sensitivity C-reactive protein (hs-CRP). Safety will be assessed at every visit.

Discussion

This pilot multicentre randomised controlled trial will explore the feasibility of further auricular acupuncture research and provide important clinical evidence for the effect and safety of auricular acupuncture on blood pressure in patients with prehypertension and stage 1 hypertension compared with usual care.

Trial registration

Clinical Research Information Service:KCT0000169
Cardiovascular rehabilitation soon after stroke using feedback-controlled robotics-assisted treadmill exercise: study protocol of a randomised controlled pilot trial
Authors: Stoller Oliver , de Bruin Eling D , Schuster-Amft Corina , Schindelholz Matthias , de Bie Rob A , Hunt Kenneth J
Published: September 2013

Background

After experiencing a stroke, most individuals also suffer from cardiac disease, are immobile and thus have low endurance for exercise. Aerobic capacity is seriously reduced in these individuals and does not reach reasonable levels after conventional rehabilitation programmes. Cardiovascular exercise is beneficial for improvement of aerobic capacity in mild to moderate stroke. However, less is known about its impact on aerobic capacity, motor recovery, and quality-of-life in severely impaired individuals. The aim of this pilot study is to explore the clinical efficacy and feasibility of cardiovascular exercise with regard to aerobic capacity, motor recovery, and quality-of-life using feedback-controlled robotics-assisted treadmill exercise in non-ambulatory individuals soon after experiencing a stroke.

Methods/Design

This will be a single-centred single blind, randomised control trial with a pre-post intervention design. Subjects will be recruited early after their first stroke (≤20 weeks) at a neurological rehabilitation clinic and will be randomly allocated to an inpatient cardiovascular exercise programme that uses feedback-controlled robotics-assisted treadmill exercise (experimental) or to conventional robotics-assisted treadmill exercise (control). Intervention duration depends on the duration of each subject’s inpatient rehabilitation period. Aerobic capacity, as the primary outcome measure, will be assessed using feedback-controlled robotics-assisted treadmill-based cardiopulmonary exercise testing. Secondary outcome measures will include gait speed, walking endurance, standing function, and quality-of-life. Outcome assessment will be conducted at baseline, after each 4-week intervention period, and before clinical discharge. Ethical approval has been obtained.

Discussion

Whether cardiovascular exercise in non-ambulatory individuals early after stroke has an impact on aerobic capacity, motor recovery, and quality-of-life is not yet known. Feedback-controlled robotics-assisted treadmill exercise is a relatively recent intervention method and might be used to train and evaluate aerobic capacity in this population. The present pilot trial is expected to provide new insights into the implementation of early cardiovascular exercise for individuals with severe motor impairment. The findings of this study may guide future research to explore the effects of early cardiovascular activation after severe neurological events.

Trial registration

This trial is registered with the Clinical Trials.gov Registry (NCT01679600).
Mixed venous O2 saturation and fluid responsiveness after cardiac or major vascular surgery
Authors: Kuiper Arjan N , Trof Ronald J , Groeneveld AB Johan
Published: September 2013

Background

It is unclear if and how SvO2 can serve as an indicator of fluid responsiveness in patients after cardiac or major vascular surgery.

Methods

This was a substudy of a randomized single-blinded clinical trial reported earlier on critically ill patients with clinical hypovolemia after cardiac or major vascular surgery. Colloid fluid loading was done for 90 min, guided by changes in pulmonary artery occlusion pressure (PAOP) or central venous pressure (CVP). Fluid responsiveness was defined as ≥15% increase in cardiac index (CI). Hemodynamics, including transpulmonary dilution-derived global end-diastolic volume index (GEDVI) and global ejection fraction (GEF), were measured and blood samples taken.

Results

Whereas baseline SvO2 (>70% in 68% of patients) did not differ, the SvO2 increased in patients responding to fluid loading (≥15% in CI in n = 26) versus those not responding (n = 11; P = 0.03). The increase in GEDVI was also greater in responders (P = 0.005). The area under the receiver operating characteristic curve for fluid responsiveness of changes in SvO2 was 0.73 (P = 0.007), with an optimal cutoff of 2%, and of those in GEDVI 0.82 (P < 0.001), while the areas did not differ. However, the value of SvO2 increases to reflect CI increases with fluid loading was greatest when GEF was ≤20% (in 53% of patients).

Conclusions

An increase in SvO2 ≥2%, irrespective of a relatively high baseline value, can thus be used as a monitor of fluid responsiveness in clinically hypovolemic patients after cardiac or major vascular surgery, particularly in those with systolic cardiac dysfunction. Fluid responsiveness concurs with increased tissue O2 delivery.
A pilot newborn screening program for Mucopolysaccharidosis type I in Taiwan
Authors: Lin Shuan-Pei , Lin Hsiang-Yu , Wang Tuen-Jen , Chang Chia-Ying , Lin Chia-Hui , Huang Sung-Fa , Tsai Chia-Chen , Liu Hsuan-Liang , Keutzer Joan , Chuang Chih-Kuang
Published: September 2013

Background

Mucopolysaccharidosis type I (MPS I) is a genetic disease caused by the deficiency of α-L-iduronidase (IDUA) activity. MPS I is classified into three clinical phenotypes called Hurler, Scheie, and Hurler-Scheie syndromes according to their clinical severity. Treatments for MPS I are available. Better outcomes are associated with early treatment, which suggests a need for newborn screening for MPS I. The goal of this study was to determine whether measuring IDUA activity in dried blood on filter paper was effective in newborn screening for MPS I.

Methods

We conducted a newborn screening pilot program for MPS I from October 01, 2008 to April 30, 2013. Screening involved measuring IDUA activity in dried blood spots from 35,285 newborns using a fluorometric assay.

Results

Of the 35,285 newborns screened, 19 did not pass the tests and had been noticed for a recall examination. After completing further recheck process, 3 were recalled again for leukocyte IDUA enzyme activity testing. Two of the three had deficient leukocyte IDUA activity. Molecular DNA analyses confirmed the diagnosis of MPS I in these two newborns.

Conclusions

It is feasible to use the IDUA enzyme assay for newborn screening. The incidence of MPS I in Taiwan estimated from this study is about 1/17,643.
The presence of heat-labile factors interfering with binding analysis of fibrinogen with ferritin in horse plasma
Authors: Takahashi Kazuma , Kondo Takashi , Yoshikawa Yasunaga , Watanabe Kiyotaka , Orino Koichi
Published: September 2013

Background

Horse fibrinogen has been identified as a plasma specific ferritin-binding protein. There are two ways in the binding of ferritin-binding protein with ferritin: one is direct binding and the other is indirect binding which is heme-mediated. The aim of this study was to analyze the binding between horse fibrinogen and ferritin.

Findings

Although fibrinogen in horse plasma did not show the binding to ferritin coated on the plate wells, after following heat-treatment (60°C, 30 min) of horse plasma, plasma fibrinogen as well as purified horse fibrinogen bound to plates coated with horse spleen ferritin, but not with its apoferritin which lost heme as well as iron after the treatment of reducing reagent. Binding of purified or plasma fibrinogen to ferritin was inhibited by hemin and Sn-protoporphyrin IX (Sn-PPIX), but not by PPIX or Zn-PPIX.

Conclusions

Heat-treatment of horse plasma enabled plasma fibrinogen to bind to plate well coated with holo-ferritin. From the binding analysis of fibrinogen and ferritin, it is suggested that horse fibrinogen recognized iron or tin in complexed with the heme- or the hemin-ring, and also suggest that some fibrinogens circulate in the form of a complex with ferritin and/or heat-labile factors which inhibit the binding of fibrinogen with ferritin.
Looking for prognosticators in ovine anaplasmosis: discriminant analysis of clinical and haematological parameters in lambs belonging to differently susceptible breeds experimentally infected with Anaplasma ovis
Authors: Ciani Elena , Alloggio Ingrid , Petazzi Ferruccio , Pieragostini Elisa
Published: September 2013

Background

A study was carried out to evaluate the response of different native sheep breeds to experimental infection with Anaplasma ovis, the most prevalent sheep tick-borne pathogen in Apulia (Southern Italy). Thirty-four lambs belonging to a Northern European breed (Suffolk) and two Southern Italian breeds (Comisana and Altamurana) were infected. Eleven clinical as well as haematological parameters were monitored at different temporal resolutions on the same subjects before and after the infection, resulting in a data set of 435 observations. The present work, aiming to further the research, presents the results of a multivariate analysis carried out to identify which parameters out of the eleven considered are the most reliable parameters to be considered as markers of the disease phenotype as well as prognosticators of practical clinical importance.

Results

Data were analysed by discriminant analysis. Out of the eleven considered variables (red blood cells, packed cell volume, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin content, haemoglobin concentration, white blood cells, neutrophils, leukocytes, platelets, rectal temperature), only seven were included in the step-wise model since significantly increasing the Mahlanobis distance between the two closest groups. Both discriminant functions resulted to be highly significant (P < 0.0001) and the percentage of variation accounted for by the first discriminant function was 63.6% of the variance in the grouping variable.

Conclusions

Taken together, the observed results stress the marked differentiation among the three breeds in terms of physio-pathological phenotypes indicating packed cell volume and red blood cell count as the most informative parameters in the routine clinical practice for A. ovis infection in sheep.
JunD/AP1 regulatory network analysis during macrophage activation in a rat model of crescentic glomerulonephritis
Authors: Srivastava Prashant K , Hull Richard P , Behmoaras Jacques , Petretto Enrico , Aitman Timothy J
Published: September 2013

Background

Function and efficiency of a transcription factor (TF) are often modulated by interactions with other proteins or TFs to achieve finely tuned regulation of target genes. However, complex TF interactions are often not taken into account to identify functionally active TF-targets and characterize their regulatory network. Here, we have developed a computational framework for integrated analysis of genome-wide ChIP-seq and gene expression data to identify the functional interacting partners of a TF and characterize the TF-driven regulatory network. We have applied this methodology in a rat model of macrophage dependent crescentic glomerulonephritis (Crgn) where we have previously identified JunD as a TF gene responsible for enhanced macrophage activation associated with susceptibility to Crgn in the Wistar-Kyoto (WKY) strain.

Results

To evaluate the regulatory effects of JunD on its target genes, we analysed data from two rat strains (WKY and WKY.LCrgn2) that show 20-fold difference in their JunD expression in macrophages. We identified 36 TFs interacting with JunD/Jun and JunD/ATF complexes (i.e., AP1 complex), which resulted in strain-dependent gene expression regulation of 1,274 target genes in macrophages. After lipopolysaccharide (LPS) stimulation we found that 2.4 fold more JunD/ATF-target genes were up-regulated as compared with JunD/Jun-target genes. The enriched 314 genes up-regulated by AP1 complex during LPS stimulation were most significantly enriched for immune response (P = 6.9 × 10-4) and antigen processing and presentation functions (P = 2.4 × 10-5), suggesting a role for these genes in macrophage LPS-stimulated activation driven by JunD interaction with Jun/ATF.

Conclusions

In summary, our integrated analyses revealed a large network of TFs interacting with JunD and their regulated targets. Our data also suggest a previously unappreciated contribution of the ATF complex to JunD-mediated mechanisms of macrophage activation in a rat model of crescentic glomerulonephritis.
Omani propolis: chemical profiling, antibacterial activity and new propolis plant sources
Authors: Popova Milena , Dimitrova Rosa , Al-Lawati Hassan Talib , Tsvetkova Iva , Najdenski Hristo , Bankova Vassya
Published: September 2013

Background

Propolis (bee glue) is a resinous honeybee product having a long history of application in many countries as a traditional remedy for treating wounds, burns, soar throat, stomach disorders, etc. It has been proved to possess beneficial biological effects, including antimicrobial, antioxidant, anti-inflammatory, cytotoxic, antiulcer, and many others. Bees gather propolis from diverse resinous plant parts and in different phytogeographic regions its chemical composition might vary significantly. In this article we report the results of the first study on the chemical profiles of propolis from Oman, its plant origin and antibacterial activity.

Results

The chemical profiles of Omani propolis extracts were obtained by GC-MS analysis after silylation. Over 50 individual compounds were identified in the samples, belonging to different compound types: sugars, polyols, hydroxy acids, fatty acids, cardanols and cardols, anacardic acids, flavan derivatives, triterpenes, prenylated flavanones and chalcones. The profiles were dissimilar from other known propolis types. They demonstrate that although Oman is not a large country, the plant sources of propolis vary significantly, even in the same apiary and the same season. Based on chemical profiles, and isolation and identification of major marker compounds (new propolis constituents), new plant sources of propolis were found: Azadiracta indica (neem tree) and Acacia spp. (most probably A. nilotica). The ethanol extracts of the studied propolis samples demonstrated activity against S. aureus (MIC < 100 μg. mL-1) and E. coli (MIC < 380 μg. mL-1).

Conclusion

Omani propolis is different form the known propolis types and demonstrates significant chemical diversity. Its most important plant source is the resin of Azadirachta indica, and as a result its typical components are С5-prenyl flavanones. Other plant sources have been identified, too, playing some role in resin collection by bees in Oman: Acacia spp. (most probably A. nilotica) and Mangifera indica. The results demonstrate also the potential of Omani propolis as antimicrobial.
Effects of supplementary butyrate on butanol production and the metabolic switch in Clostridium beijerinckii NCIMB 8052: genome-wide transcriptional analysis with RNA-Seq
Authors: Wang Yi , Li Xiangzhen , Blaschek Hans P
Published: September 2013

Background

Butanol (n-butanol) has high values as a promising fuel source and chemical feedstock. Biobutanol is usually produced by the solventogenic clostridia through a typical biphasic (acidogenesis and solventogenesis phases) acetone-butanol-ethanol (ABE) fermentation process. It is well known that the acids produced in the acidogenic phase are significant and play important roles in the switch to solventogenesis. However, the mechanism that triggers the metabolic switch is still not clear.

Results

Sodium butyrate (40 mM) was supplemented into the medium for the ABE fermentation with Clostridium beijerinckii NCIMB 8052. With butyrate addition (reactor R1), solvent production was triggered early in the mid-exponential phase and completed quickly in < 50 h, while in the control (reactor R2), solventogenesis was initiated during the late exponential phase and took > 90 h to complete. Butyrate supplementation led to 31% improvement in final butanol titer, 58% improvement in sugar-based yield, and 133% improvement in butanol productivity, respectively. The butanol/acetone ratio was 2.4 versus 1.8 in the control, indicating a metabolic shift towards butanol production due to butyrate addition. Genome-wide transcriptional dynamics was investigated with RNA-Seq analysis. In reactor R1, gene expression related to solventogenesis was induced about 10 hours earlier when compared to that in reactor R2. Although the early sporulation genes were induced after the onset of solventogenesis in reactor R1 (mid-exponential phase), the sporulation events were delayed and uncoupled from the solventogenesis. In contrast, in reactor R2, sporulation genes were induced at the onset of solventogenesis, and highly expressed through the solventogenesis phase. The motility genes were generally down-regulated to lower levels prior to stationary phase in both reactors. However, in reactor R2 this took much longer and gene expression was maintained at comparatively higher levels after entering stationary phase.

Conclusions

Supplemented butyrate provided feedback inhibition to butyrate formation and may be re-assimilated through the reversed butyrate formation pathway, thus resulting in an elevated level of intracellular butyryl phosphate, which may act as a phosphate donor to Spo0A and then trigger solventogenesis and sporulation events. High-resolution genome-wide transcriptional analysis with RNA-Seq revealed detailed insights into the biochemical effects of butyrate on solventogenesis related-events at the gene regulation level.