bluuebunny/crossref_metadata_2025 huggingface dataset:
The organ-specific expression of terpene synthase genes contributes to the terpene hydrocarbon composition of chamomile essential oils
Authors: Irmisch Sandra , Krause Sandra T , Kunert Grit , Gershenzon Jonathan , Degenhardt Jörg , Köllner Tobias G
Published: June 2012

Background

The essential oil of chamomile, one of the oldest and agronomically most important medicinal plant species in Europe, has significant antiphlogistic, spasmolytic and antimicrobial activities. It is rich in chamazulene, a pharmaceutically active compound spontaneously formed during steam distillation from the sesquiterpene lactone matricine. Chamomile oil also contains sesquiterpene alcohols and hydrocarbons which are produced by the action of terpene synthases (TPS), the key enzymes in constructing terpene carbon skeletons.

Results

Here, we present the identification and characterization of five TPS enzymes contributing to terpene biosynthesis in chamomile (Matricaria recutita). Four of these enzymes were exclusively expressed in above-ground organs and produced the common terpene hydrocarbons (−)-(E)-β-caryophyllene (MrTPS1), (+)-germacrene A (MrTPS3), (E)-β-ocimene (MrTPS4) and (−)-germacrene D (MrTPS5). A fifth TPS, the multiproduct enzyme MrTPS2, was mainly expressed in roots and formed several Asteraceae-specific tricyclic sesquiterpenes with (−)-α-isocomene being the major product. The TPS transcript accumulation patterns in different organs of chamomile were consistent with the abundance of the corresponding TPS products isolated from these organs suggesting that the spatial regulation of TPS gene expression qualitatively contribute to terpene composition.

Conclusions

The terpene synthases characterized in this study are involved in the organ-specific formation of essential oils in chamomile. While the products of MrTPS1, MrTPS2, MrTPS4 and MrTPS5 accumulate in the oils without further chemical alterations, (+)-germacrene A produced by MrTPS3 accumulates only in trace amounts, indicating that it is converted into another compound like matricine. Thus, MrTPS3, but also the other TPS genes, are good markers for further breeding of chamomile cultivars rich in pharmaceutically active essential oils.
Oral versus intravenous proton pump inhibitors in preventing re-bleeding for patients with peptic ulcer bleeding after successful endoscopic therapy
Authors: Yen Hsu-Heng , Yang Chia-Wei , Su Wei-Wen , Soon Maw-Soan , Wu Shun-Sheng , Lin Hwai-Jeng
Published: June 2012

Background

High dose intravenous proton pump inhibitor after endoscopic therapy for peptic ulcer bleeding has been recommended as adjuvant therapy. Whether oral proton pump inhibitor can replace intravenous proton pump inhibitor in this setting is unknown. This study aims to compare the clinical efficacy of oral and intravenous proton pump inhibitor after endoscopic therapy.

Methods

Patients with high-risk bleeding peptic ulcers after successful endoscopic therapy were randomly assigned as oral lansoprazole or intravenous esomeprazole group. Primary outcome of the study was re-bleeding rate within 14 days. Secondary outcome included hospital stay, volume of blood transfusion, surgical intervention and mortality within 1 month.

Results

From April 2010 to Feb 2011, 100 patients were enrolled in this study. The re-bleeding rates were 4% (2/50) in the intravenous group and 4% (2/50) in the oral group. There was no difference between the two groups with regards to the hospital stay, volume of blood transfusion, surgery or mortality rate. The mean duration of hospital stay was 1.8 days in the oral lansoprazole group and 3.9 days in the intravenous esomeprazole group (p > 0.01).

Conclusion

Patients receiving oral proton pump inhibitor have a shorter hospital stay. There is no evidence of a difference in clinical outcomes between oral and intravenous PPI treatment. However, the study was not powered to prove equivalence or non-inferiority. Future studies are still needed.

Trial registration

NCT01123031
Epidemiology and aetiology of dialysis-treated end-stage kidney disease in Libya
Authors: Alashek Wiam A , McIntyre Christopher W , Taal Maarten W
Published: June 2012

Background

The extent and the distribution of end stage kidney disease (ESKD) in Libya have not been reported despite provision of dialysis over 4 decades. This study aimed to develop the first comprehensive description of the epidemiology of dialysis-treated ESKD in Libya.

Methods

Structured demographic and clinical data were obtained regarding all adult patients treated at all maintenance dialysis facilities (n=39) in Libya from May to September 2009. Subsequently data were collected prospectively on all new patients who started dialysis from September 2009 to August 2010. Population estimates were obtained from the Libyan national statistics department. The age and gender breakdown of the population in each region was obtained from mid-2009 population estimates based on 2006 census data.

Results

The prevalence of dialysis-treated ESKD was 624 per million population (pmp). 85% of prevalent patients were aged <65 years and 58% were male. The prevalence of ESKD varied considerably with age with a peak at 55–64 years (2475 pmp for males; 2197 pmp for females). The annual incidence rate was 282 pmp with some regional variation and a substantially higher rate in the South (617 pmp). The most common cause of ESKD among prevalent and incident patients was diabetes. Other important causes were glomerulonephritis, hypertensive nephropathy and congenital or hereditary diseases.

Conclusions

Libya has a relatively high prevalence and incidence of dialysis-treated ESKD. As the country prepares to redevelop its healthcare system it is hoped that these data will guide strategies for the prevention of CKD and planning for the provision of renal replacement therapy.
Estimation of salt intake from spot urine samples in patients with chronic kidney disease
Authors: Ogura Makoto , Kimura Ai , Takane Koki , Nakao Masatsugu , Hamaguchi Akihiko , Terawaki Hiroyuki , Hosoya Tatsuo
Published: June 2012

Background

High salt intake in patients with chronic kidney disease (CKD) may cause high blood pressure and increased albuminuria. Although, the estimation of salt intake is essential, there are no easy methods to estimate real salt intake.

Methods

Salt intake was assessed by determining urinary sodium excretion from the collected urine samples. Estimation of salt intake by spot urine was calculated by Tanaka’s formula. The correlation between estimated and measured sodium excretion was evaluated by Pearson´s correlation coefficients. Performance of equation was estimated by median bias, interquartile range (IQR), proportion of estimates within 30% deviation of measured sodium excretion (P30) and root mean square error (RMSE).The sensitivity and specificity of estimated against measured sodium excretion were separately assessed by receiver-operating characteristic (ROC) curves.

Results

A total of 334 urine samples from 96 patients were examined. Mean age was 58 ± 16 years, and estimated glomerular filtration rate (eGFR) was 53 ± 27 mL/min. Among these patients, 35 had CKD stage 1 or 2, 39 had stage 3, and 22 had stage 4 or 5. Estimated sodium excretion significantly correlated with measured sodium excretion (R = 0.52, P < 0.01). There was apparent correlation in patients with eGFR <30 mL/min (R = 0.60, P < 0.01). Moreover, IQR was lower and P30 was higher in patients with eGFR < 30 mL/min. Estimated sodium excretion had high accuracy to predict measured sodium excretion, especially when the cut-off point was >170 mEq/day (AUC 0.835).

Conclusions

The present study demonstrated that spot urine can be used to estimate sodium excretion, especially in patients with low eGFR.
Vitamin D deficiency in girls from South Brazil: a cross-sectional study on prevalence and association with vitamin D receptor gene variants
Authors: Santos Betânia R , Mascarenhas Luis P G , Satler Fabíola , Boguszewski Margaret C S , Spritzer Poli Mara
Published: June 2012

Background

Vitamin D deficiency has been associated with a multitude of disorders including diabetes, defective insulin secretion as well as rickets and poor bone health. Vitamin D is also a concern during childhood and adolescence and has been reported in girls from South Brazil. We determined the prevalence of vitamin D deficiency in girls from South Brazil and investigated whether the genotypic distribution of the BsmI, ApaI and TaqI polymorphisms of the VDR gene and their haplotypes were associated with vitamin D levels.

Methods

Cross-sectional study including 234 apparently healthy girls aged 7 to 18 years. Height and weight were measured for calculation of body mass index (BMI) percentiles for age. Plasma levels of 25-hydroxyvitamin D [25(OH)D] were assessed. Participants were genotyped for ApaI (rs7975232), TaqI (rs731236), and BsmI (rs1544410) SNPs.

Results

The median and interquartile range (25-75%) of BMI percentile was 62.0 (33.3 – 84.9). The frequency of overweight/obesity was 24.9%. Circulating levels of 25(OH)D (≥ 30 ng/mL) were adequate in 9.4%; insufficient in 54.3% (20–29 ng/mL); and deficient in 36.3% (< 20 ng/mL). Genotype frequencies were GG = 47.0%, GA = 41.5%, and AA = 11.5% for BsmI; GG = 16.7%, GT = 52.6%, and TT = 30.8% for ApaI; TT = 46.2%, TC = 44.9% and CC = 9.0% for TaqI. Genotypes with no gene variance (ancestral wild genotype) of BsmI (GG vs. GA + AA, two-tailed Student’s t-test p < 0.001), ApaI (GG vs. GT + TT, two-tailed Student’s t-test p = 0.031) and TaqI (TT vs. TC + CC, two-tailed Student’s t-test p = 0.005) SNPs and the GGT haplotype (two-tailed Student’s t-test p = 0.036) were significantly associated with lower 25(OH)D levels.

Conclusions

25-hydroxyvitamin D deficiency and insufficiency were highly prevalent in this sample. The BsmI, ApaI and TaqI wild variants of the VDR gene, as well as the GGT haplotype, were associated with lower vitamin D levels, suggesting that VDR gene polymorphisms could be linked to higher susceptibility to vitamin D deficiency in a sub-population of children and adolescents.
The effects of low dose X-irradiation on osteoblastic MC3T3-E1 cells in vitro
Authors: Xu Wei , Xu Lan , Chen Ming , Mao Yong Tao , Xie Zong Gang , Wu Shi Liang , Dong Qi Rong
Published: June 2012

Background

It has been indicated that moderate or high dose of X-irradiation could delay fracture union and cause osteoradionecrosis, in part, mediated by its effect on proliferation and differentiation of osteoblasts. However, whether low dose irradiation (LDI) has similar roles on osteoblasts is still unknown. In this study, we investigated whether and to what extent LDI could affect the proliferation, differentiation and mineralization of osteoblasts in vitro.

Methods

The MC3T3-E1 cells were exposed to single dose of X-irradiation with 0, 0.1, 0.5, 1.0 Gy respectively. Cell proliferation, apoptosis, alkaline phosphatase (ALP) activity, and mineralization was evaluated by methylthiazoletetrazolium (MTT) and bromodeoxyuridine (BrdU) assay, flow cytometry, ALP viability kit and von Kossa staining, respectively. Osteocalcin (OCN) and core-binding factor α1 (Cbfα1) expressions were measured by real time-PCR and western blot, respectively.

Results

The proliferation of the cells exposed to 2.0 Gy was significantly lower than those exposed to ≤1.0 Gy (p < 0.05) from Day 4 to Day 8, measured by MTT assay and BrdU incorporation. For cells exposed to ≤1.0 Gy, increasing dosages of X-irradiation had no significant effect on cell proliferation and apoptosis. Importantly, LDI of 0.5 and 1 Gy increased ALP activities and mineralized nodules of MC3T3-E1 cells. In addition, mRNA and protein expressions of OCN and Cbfα1 were also markedly increased after treatment with LDI at 0.5 and 1 Gy.

Conclusions

LDI have different effects on proliferation and differentiation of osteoblasts from those of high dose of X-irradiation, which might suggest that LDI could lead to promotion of frature healing through enhancing the differentiation and mineralization of osteoblasts.
Upregulated expression of Annexin II is a prognostic marker for patients with gastric cancer
Authors: Zhang Qi , Ye Zaiyuan , Yang Qiong , He Xujun , Wang Huiju , Zhao Zhongsheng
Published: June 2012

Background

The role of annexin II in the development and progression of gastric cancer was explored.

Methods

Real-time PCR was conducted to detect annexin II and S100A6 mRNA expression. Protein expressions of annexin II and S100A6 were also examined by immunohistochemistry in 436 clinicopathologically characterized gastric cancer cases.

Results

The expression of annexin II and S100A6 mRNA differ significantly among gastric tumor tissue and matched non-cancerous gastric mucosa. Protein levels of annexin II and S100A6 were up-regulated in gastric cancer compared with adjacent non-cancerous tissues. High expression of annexin II correlated with age, location of tumor, size of tumor, differentiation, histological type, depth of invasion, vessel invasion, lymph node metastasis, distant metastasis and Tumor, Node, Metastasis (TNM) stage, and also with expression of S100A6. Further multivariate analysis suggested that expression of annexin II and S100A6 were independent prognostic indicators for gastric cancer.

Cumulative five-year survival rates of patients with high expression of both annexin II and S100A6 was significantly lower than those with low expression of both.

Conclusion

Expression of annexin II in gastric cancer was significantly associated with depth of invasion, lymph node metastasis and distant metastasis, TNM stage, high S100A6 expression, and poor prognosis. Annexin II and S100A6 proteins could be useful prognostic marker to predict tumor progression and prognosis in gastric cancer.
BRAFV600E status and clinical characteristics in solitary and multiple papillary thyroid carcinoma: experience of 512 cases at a clinical center in China
Authors: Zheng Xiangqian , Xia Tingting , Lin Lin , Gao Songyuan , Lee Yigong , Yu Yang , Wei Songfeng , Gao Ming
Published: June 2012

Background

Papillary thyroid carcinoma (PTC) is one of the most frequent endocrine malignancies. In most cases, it often presents as multifocal tumor. It has been reported that multifocal tumors are associated with elevated risk of lymph node and distant metastases. Multifocality is also one of the factors predicting prognosis. Recent studies show that BRAFV600E mutation occurs more frequently in aggressive PTC. The purpose of this study was to evaluate BRAFV600E status and clinicopathological features in multiple and solitary PTC.

Methods

We performed a retrospective study to analyze 512 PTC cases who received surgery, including 376 solitary PTCs and 136 multiple PTCs.

Results

Multiple PTC is more related to lymph node metastasis and vascular invasion than solitary PTC. However, the distant metastasis rate and 10-year survival rate showed no difference between these two groups. BRAFV600E mutation status was more frequent in multiple PTC patients with lymph node metastasis and late stage at diagnosis.

Conclusion

BRAFV600E mutation is most commonly associated with extra-thyroidal extension and lymph node metastasis in PTC. Multiple PTC patients with young age, large tumors and BRAFV600E mutation should be followed carefully. Our study provides useful information for PTC patients’ followup and treatment.
High level of miR-221/222 confers increased cell invasion and poor prognosis in glioma
Authors: Zhang Chunzhi , Zhang Junxia , Hao Jianwei , Shi Zhendong , Wang Yingyi , Han Lei , Yu Shizhu , You Yongping , Jiang Tao , Wang Jinhuan , Liu Meili , Pu Peiyu , Kang Chunsheng
Published: June 2012

Background

MiR-221 and miR-222 (miR-221/222), upregulated in gliomas, can regulate glioma cell cycle progression and apoptosis, respectively. However, the association of miR-221/222 with glioma cell invasion and survival remains unknown.

Methods

Invasion capability of miR-221/222 was detected by mutiple analyses, including diffusion tensor imaging (DTI), transwell, wound healing and nude mouse tumor xenograft model assay. Further, the target of miR-221/222 was determined by luciferase reporter, western blot and gene rescue assay. The association of miR-221/222 with outcome was examined in fifty glioma patients.

Results

MiR-221/222 expression was significantly increased in high-grade gliomas compared with low-grade gliomas, and positively correlated with the degree of glioma infiltration. Over-expression of miR-221/222 increased cell invasion, whereas knockdown of miR-221/222 decreased cell invasion via modulating the levels of the target, TIMP3. Introduction of a TIMP3 cDNA lacking 3’ UTR abrogated miR-221/222-induced cell invasion. In addition, knockdown of miR-221/222 increased TIMP3 expression and considerably inhibited tumor growth in a xenograft model. Finally, the increased level of miR-221/222 expression in high-grade gliomas confers poorer overall survival.

Conclusions

The present data indicate that miR-221 and miR-222 directly regulate cell invasion by targeting TIMP3 and act as prognostic factors for glioma patients.
Reference-free SNP calling: improved accuracy by preventing incorrect calls from repetitive genomic regions
Authors: Dou Jinzhuang , Zhao Xiqiang , Fu Xiaoteng , Jiao Wenqian , Wang Nannan , Zhang Lingling , Hu Xiaoli , Wang Shi , Bao Zhenmin
Published: June 2012

Background

Single nucleotide polymorphisms (SNPs) are the most abundant type of genetic variation in eukaryotic genomes and have recently become the marker of choice in a wide variety of ecological and evolutionary studies. The advent of next-generation sequencing (NGS) technologies has made it possible to efficiently genotype a large number of SNPs in the non-model organisms with no or limited genomic resources. Most NGS-based genotyping methods require a reference genome to perform accurate SNP calling. Little effort, however, has yet been devoted to developing or improving algorithms for accurate SNP calling in the absence of a reference genome.

Results

Here we describe an improved maximum likelihood (ML) algorithm called iML, which can achieve high genotyping accuracy for SNP calling in the non-model organisms without a reference genome. The iML algorithm incorporates the mixed Poisson/normal model to detect composite read clusters and can efficiently prevent incorrect SNP calls resulting from repetitive genomic regions. Through analysis of simulation and real sequencing datasets, we demonstrate that in comparison with ML or a threshold approach, iML can remarkably improve the accuracy of de novo SNP genotyping and is especially powerful for the reference-free genotyping in diploid genomes with high repeat contents.

Conclusions

The iML algorithm can efficiently prevent incorrect SNP calls resulting from repetitive genomic regions, and thus outperforms the original ML algorithm by achieving much higher genotyping accuracy. Our algorithm is therefore very useful for accurate de novo SNP genotyping in the non-model organisms without a reference genome.

Reviewers

This article was reviewed by Dr. Richard Durbin, Dr. Liliana Florea (nominated by Dr. Steven Salzberg) and Dr. Arcady Mushegian.
Accuracy and inter-observer variability of 3D versus 4D cone-beam CT based image-guidance in SBRT for lung tumors
Authors: Sweeney Reinhart A , Seubert Benedikt , Stark Silke , Homann Vanessa , Müller Gerd , Flentje Michael , Guckenberger Matthias
Published: June 2012

Background

To analyze the accuracy and inter-observer variability of image-guidance (IG) using 3D or 4D cone-beam CT (CBCT) technology in stereotactic body radiotherapy (SBRT) for lung tumors.

Materials and methods

Twenty-one consecutive patients treated with image-guided SBRT for primary and secondary lung tumors were basis for this study. A respiration correlated 4D-CT and planning contours served as reference for all IG techniques. Three IG techniques were performed independently by three radiation oncologists (ROs) and three radiotherapy technicians (RTTs). Image-guidance using respiration correlated 4D-CBCT (IG-4D) with automatic registration of the planning 4D-CT and the verification 4D-CBCT was considered gold-standard. Results were compared with two IG techniques using 3D-CBCT: 1) manual registration of the planning internal target volume (ITV) contour and the motion blurred tumor in the 3D-CBCT (IG-ITV); 2) automatic registration of the planning reference CT image and the verification 3D-CBCT (IG-3D). Image quality of 3D-CBCT and 4D-CBCT images was scored on a scale of 1–3, with 1 being best and 3 being worst quality for visual verification of the IGRT results.

Results

Image quality was scored significantly worse for 3D-CBCT compared to 4D-CBCT: the worst score of 3 was given in 19 % and 7.1 % observations, respectively. Significant differences in target localization were observed between 4D-CBCT and 3D-CBCT based IG: compared to the reference of IG-4D, tumor positions differed by 1.9 mm ± 0.9 mm (3D vector) on average using IG-ITV and by 3.6 mm ± 3.2 mm using IG-3D; results of IG-ITV were significantly closer to the reference IG-4D compared to IG-3D. Differences between the 4D-CBCT and 3D-CBCT techniques increased significantly with larger motion amplitude of the tumor; analogously, differences increased with worse 3D-CBCT image quality scores. Inter-observer variability was largest in SI direction and was significantly larger in IG using 3D-CBCT compared to 4D-CBCT: 0.6 mm versus 1.5 mm (one standard deviation). Inter-observer variability was not different between the three ROs compared to the three RTTs.

Conclusions

Respiration correlated 4D-CBCT improves the accuracy of image-guidance by more precise target localization in the presence of breathing induced target motion and by reduced inter-observer variability.
Neocentric X-chromosome in a girl with Turner-like syndrome
Authors: Hemmat Morteza , Wang Boris T , Warburton Peter E , Yang Xiaojing , Boyar Fatih Z , El Naggar Mohammed , Anguiano Arturo
Published: June 2012

Background

Neocentromeres are rare human chromosomal aberrations in which a new centromere has formed in a previously non-centromeric location. We report the finding of a structurally abnormal X chromosome with a neocentromere in a 15-year-old girl with clinical features suggestive of Turner syndrome, including short stature and primary amenorrhea.

Result

G-banded chromosome analysis revealed a mosaic female karyotype involving two abnormal cell lines. One cell line (84% of analyzed metaphases) had a structurally abnormal X chromosome (duplication of the long arm and deletion of the short arm) and a normal X chromosome. The other cell line (16% of cells) exhibited monosomy X. C-banding studies were negative for the abnormal X chromosome. FISH analysis revealed lack of hybridization of the abnormal X chromosome with both the X centromere-specific probe and the “all human centromeres” probe, a pattern consistent with lack of the X chromosome endogenous centromere. A FISH study using an XIST gene probe revealed the presence of two XIST genes, one on each long arm of the iso(Xq), required for inactivation of the abnormal X chromosome. R-banding also demonstrated inactivation of the abnormal X chromosome. An assay for centromeric protein C (CENP-C) was positive on both the normal and the abnormal X chromosomes. The position of CENP-C in the abnormal X chromosome defined a neocentromere, which explains its mitotic stability. The karyotype is thus designated as 46,X,neo(X)(qter- > q12::q12- > q21.2- > neo- > q21.2- > qter)[42]/45,X[8], which is consistent with stigmata of Turner syndrome. The mother of this patient has a normal karyotype; however, the father was not available for study.

Conclusion

To our knowledge, this is the first case of mosaic Turner syndrome involving an analphoid iso(Xq) chromosome with a proven neocentromere among 90 previously described cases with a proven neocentromere.
Administration of imatinib after allogeneic hematopoietic stem cell transplantation may improve disease-free survival for patients with Philadelphia chromosome-positive acute lymphobla stic leukemia
Authors: Chen Huan , Liu Kai-yan , Xu Lan-ping , Liu Dai-hong , Chen Yu-hong , Zhao Xiang-yu , Han Wei , Zhang Xiao-hui , Wang Yu , Zhang Yuan-yuan , Qin Ya-zhen , Liu Yan-rong , Huang Xiao-jun
Published: June 2012

Background

Maintenance therapy with imatinib during the post-transplant period has been used for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL); however, its efficacy has not been demonstrated. A study was designed to investigate the safety of imatinib and its efficacy in preventing hematological relapse and improving disease-free survival (DFS) when administered after allogeneic hematopoietic stem cell transplantation (allo-HCT).

Methods

Patients with Ph + ALL that received allo-HCT were enrolled in the study. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect BCR-ABL transcript levels. Imatinib therapy was initiated if patient neutrophil counts were > 1.0 × 109/L and platelet counts were > 50.0 × 109/L, or if they displayed either elevated BCR-ABL transcript levels in two consecutive tests, or a BCR-ABL transcript level ≥ 10-2 after initial engraftment. Patients receiving imatinib after relapse were assigned to the non-imatinib group. The imatinib treatment was scheduled for 3–12 months, until BCR-ABL transcript levels were negative at least for three consecutive tests or complete molecular remission was sustained for at least 3 months.

Results

A total of 82 patients were enrolled. Sixty-two patients initiated imatinib therapy post-HCT. Imatinib therapy was initiated at a median time of 70 days post-HCT. Grade 3–4 adverse events (AEs) occurred in 17.7% of patients. Ten patients (16.1%) terminated imatinib therapy owing to AEs. Among the patients in imatinib and non-imatinib groups, the estimated 5-year relapse rate was 10.2% and 33.1% (p = 0.016), and the 5-year probability of DFS was 81.5% and 33.5% (p = 0.000) with the median follow-up of 31 months (range, 2.5-76 months) and 24.5 months (range, 4–72 months), respectively. Multivariate analysis identified imatinib maintenance therapy post-HCT as an independent prognostic factor for DFS (p = 0.000, hazard ratio [HR] =4.8) and OS (p = 0.000, HR = 6.2).

Conclusions

These results indicate that relapse rate can be reduced and DFS may be improved in Ph + ALL patients with imatinib maintenance therapy after HCT. BCR-ABL monitoring by qRT-PCR can guide maintenance therapy with imatinib including initiation time and treatment duration after allo-HCT.
Glucose tolerance status is a better predictor of diabetes and cardiovascular outcomes than metabolic syndrome: a prospective cohort study
Authors: Furtado de Souza Camila , Dalzochio Mériane Boeira , de Oliveira Francisco Jorge Arsego , Gross Jorge Luiz , Leitão Cristiane Bauermann
Published: June 2012

Backround

To evaluate the importance of oral glucose tolerance test (OGTT) in predicting diabetes and cardiovascular disease in patients with and without Metabolic Syndrome from a population treated in a primary care unit.

Research design and methods

A prospective cohort study was conducted with subjects regularly attending the primary care unit of Hospital de Clínicas de Porto Alegre. Participants underwent a 75 g OGTT. Metabolic syndrome definition was based on the criteria of IDF/AHA/NHLBI-2010.

Results

Participants mean age was 61 ± 12 years (males: 38%; whites: 67%). Of the 148 subjects included, 127 (86%) were followed for 36 ± 14 months, 21 (14%) were lost. Subjects were classified into four groups based on baseline OGTT: 29% normal (n = 43), 28% impaired fasting glucose (IFG; n = 42), 26% impaired glucose tolerance (IGT; n = 38), and 17% diabetes (n = 25). Metabolic syndrome prevalence was lower in normal group (28%), intermediate in IFG (62%) and IGT (65%) groups, and higher among subjects with diabetes (92%; P <0.001). Incidence of diabetes increased along with the stages of glucose metabolism disturbance (normal: 0%, IFG: 16%, IGT: 28%; P = 0.004). No patient with normal OGTT developed diabetes, regardless metabolic syndrome presence. Diabetes at baseline was the major determinant of cardiovascular disease occurrence (normal: 0%, IFG: 4%, IGT: 0%, diabetes: 24%; P = 0.001). In Cox-regression analysis, only the 2 h OGTT results were associated with diabetes (OR = 1.03; 95%CI 1.01–1.06; P <0.001) and cardiovascular disease development (OR = 1.013; 95%CI 1.002–1.025; P = 0.024).

Conclusions

In this sample of subjects undergoing diabetes screening, the OGTT predicted diabetes and cardiovascular disease more effectively than the metabolic syndrome status.
Analysis of traumatic injuries presenting to a referral hospital emergency department in Moshi, Tanzania
Authors: Casey Erica R , Muro Florida , Thielman Nathan M , Maya Elifuraha , Ossmann Eric W , Hocker Michael B , Gerardo Charles J
Published: June 2012

Background

Injuries represent a significant and growing public health concern in the developing world, yet their impact on patients and the emergency health-care system in the countries of East Africa has received limited attention. This study evaluates the magnitude and scope of injury related disorders in the population presenting to a referral hospital emergency department in northern Tanzania.

Methods

A retrospective chart review of patients presenting to the emergency department at Kilimanjaro Christian Medical Centre was performed. A standardized data collection form was used for data abstraction from the emergency department logbook and the complete medical record for all injured patients. Patient demographics, mechanism of injury, location, type and outcomes were recorded.

Results

Ten thousand six hundred twenty-two patients presented to the emergency department for evaluation and treatment during the 7-month study period. One thousand two hundred twenty-four patients (11.5%) had injuries. Males and individuals aged 15 to 44 years were most frequently injured, representing 73.4% and 57.8%, respectively. Road traffic injuries were the most common mechanism of injury, representing 43.9% of injuries. Head injuries (36.5%) and extremity injuries (59.5%) were the most common location of injury. The majority of injured patients, 59.3%, were admitted from the emergency department to the hospital wards, and 5.6%, required admission to an intensive care unit. Death occurred in 5.4% of injured patients.

Conclusions

These data give a detailed and more robust picture of the patient demographics, mechanisms of injury, types of injury and patient outcomes from similar resource-limited settings.
A review of official data obtained from dog control records generated by the dog control service of county cork, Ireland during 2007
Authors: O’Sullivan Edmond N , Hanlon Alison J
Published: June 2012

Background

There are no peer reviewed data on dog control records from an official agency in Ireland. In order to address this, a total of 2,669 official dog control service records generated during 2007 by Cork County Council dog control service were reviewed.

Results

Over 70 percent of records related to unwanted dogs and dogs not under their owners control. Stray dogs were collected by the service regularly throughout the year but with notable increase in voluntary surrenders by owners from January through to April. The majority of dogs collected or surrendered were male (2:1 ratio), of medium size, described as having a friendly temperament and were not wearing a neck collar. The Crossbreed and Greyhound breeds were more frequently collected as strays, while Greyhounds and German Shepherds were more frequently voluntarily surrendered by their owner. Restricted breeds such as Pit Bull terriers, German Shepherds and Rottweilers were more frequently reported by members of the public for aggressive behaviour while the only restricted breed reported for biting or snapping was the German Shepherd.

Conclusions

Routine recording of dog control services in County Cork provide data on responsible dog ownership including the licensing of breeds, and surrender of owned dogs and the collection of stray dogs. Data capture and utilisation of dog control services by local authorities has potential to inform policy on responsible dog ownership and education programmes.
Production and downstream processing of (1→3)-β-D-glucan from mutant strain of Agrobacterium sp. ATCC 31750
Authors: Kalyanasundaram Gayathiri T , Doble Mukesh , Gummadi Sathyanarayana N
Published: June 2012

We isolated a mutant that produced higher levels of curdlan than the wild strain Agrobacterium sp. ATCC 31750 by chemical mutagenesis using N-methyl-N-nitro-nitrosoguanidine. The mutant strain produced 66 g/L of curdlan in 120 h with a yield of (0.88) while, the wild strain produced 41 g/L in 120 h with a yield of (0.62) in a stirred bioreactor. The mutant could not produce curdlan when the pH was shifted from 7.0 to 5.5 after nitrogen depletion as followed for wild strain. In contrast, pH optimum for cell growth and curdlan production for mutant was found to be 7.0. We optimized the downstream processing of curdlan by varying different volumes of NaOH and HCl for extraction and precipitation of curdlan. The molecular weight of the purified curdlan from the wild and mutant strain was 6.6 × 105 Da and 5.8 × 105 Da respectively. The monosaccharide analyses confirm that curdlan from both wild and mutant strain contains only glucose units. From the NMR and FTIR data, it has been confirmed that curdlan was exclusively composed of β (1 → 3)-D-glucan residues.
Adenosine receptor expression in rheumatoid synovium: a basis for methotrexate action
Authors: Stamp Lisa K , Hazlett Jody , Roberts Rebecca L , Frampton Christopher , Highton John , Hessian Paul A
Published: June 2012

Introduction

Methotrexate (MTX) exerts at least part of its anti-inflammatory effects through adenosine receptors (ADOR). The aims of this study were to determine the expression of all four adenosine receptor genes (ADORA1, ADORA2A, ADORA2B, ADORA3 and ADORA3variant) in rheumatoid synovial tissue and any influence of MTX exposure on this expression. Furthermore, we investigated whether polymorphisms within ADORA3 were associated with response and/or adverse effects associated with MTX.

Methods

Adenosine receptor gene expression was undertaken using PCR in 20 rheumatoid arthritis (RA) synovial samples. A separate cohort of 225 RA patients receiving MTX was genotyped for SNPs in the ADORA3 receptor gene. Double immunofluorescence was used to identify cells expressing ADOR protein.

Results

All ADOR genes were expressed in all synovial samples. ADORA3 and A3variant were the dominant subtypes expressed irrespective of MTX therapy. Expression of ADORA2A and ADORA2B was increased in patients receiving MTX compared to those not receiving MTX. There was no association between the ADORA3rs1544224 SNP and high and low disease activity or MTX-associated adverse effects. ADORA2B protein expression was most obvious in vascular endothelial cells whereas ADORA3 protein was more abundant and expressed by synovial fibroblasts.

Conclusions

We have shown that adenosine receptors are expressed in RA synovium. There is differential expression of receptors such that ADORA3 is expressed at significantly higher levels. This evidence demonstrates the potential for MTX to exert its anti-inflammatory effects at the primary site of pathology within the joints of patients with RA.
TheDrosophilaRZZ complex: roles in membrane traffic and cytokinesis
Authors: Wainman Alan , Giansanti Maria Grazia , Goldberg Michael L. , Gatti Maurizio
Published: June 2012

The Zw10 protein, in the context of the conserved Rod-Zwilch-Zw10 (RZZ) complex, is a kinetochore component required for proper activity of the spindle assembly checkpoint in both Drosophila and mammals. In mammalian and yeast cells, the Zw10 homologues, together with the conserved RINT1/Tip20p and NAG/Sec39p proteins, form a second complex involved in vesicle transport between Golgi and ER. However, it is currently unknown whether Zw10 and the NAG family member Rod are also involved in Drosophila membrane traffic. Here we show that Zw10 is enriched at both the Golgi stacks and the ER of Drosophila spermatocytes. Rod is concentrated at the Golgi but not at the ER, while Zwilch does not accumulate in any membrane compartment. Mutations in zw10 and RNAi against the Drosophila homologue of RINT1 (rint1) cause strong defects in Golgi morphology and reduce the number of Golgi stacks. Mutations in rod also affect Golgi morphology, while zwilch mutants do not exhibit gross Golgi defects. Loss of either Zw10 or Rint1 results in frequent failures of spermatocyte cytokinesis, whereas Rod or Zwilch are not required for this process. Spermatocytes lacking zw10 or rint1 function assemble regular central spindles and acto-myosin rings, but furrow ingression halts prematurely due to defective plasma membrane addition. Collectively, our results suggest that Zw10 and Rint1 cooperate in the ER-Golgi traffic and in plasma membrane formation during spermatocyte cytokinesis. Our findings further suggest that Rod plays a Golgi-related function that is not required for spermatocyte cytokinesis.
The antimicrobial activity of the alcohols fromMusca domestica
Authors: Gołębiowski Marek , Dawgul Małgorzata , Kamysz Wojciech , Boguś Mieczysława I. , Wieloch Wioletta , Włóka Emilia , Paszkiewicz Monika , Przybysz Elżbieta , Stepnowski Piotr
Published: June 2012

The total cuticular alcohols in larvae, male, and female of M. domestica were detected in comparable amounts (4.59, 3.95 and 4.03 µg/g of the insect body, respectively). The total cuticular alcohols in pupae occurred in smaller quantities (2.16 µg/g of the insect body). The major free alcohol in M. domestica larvae was C12:0 (70.4%). Internal alcohols of M. domestica larvae were not found. Among cuticular pupae alcohols, C12:0 (31.0%) was the most abundant compound. Other alcohols were detected in smaller amounts from 3.7% (C14:0) to 14.4% (C16:0). In the internal lipids of pupae, only 5 alcohols were identified in traces. Most abundant alcohol in male was C24:0 (57.5%). The percentage content of cuticular C24:0 in male and female were significantly higher than those of cuticular lipids in larvae and pupae and compromised 57.5%, 36.5%, 0.9% and 5.6%, respectively. Only two alcohols were present in internal lipids of male in traces (C18:0 and C20:0). Most abundant cuticular alcohols in female were C24:0 (36.5%) and C12:0 (26.8%). Other alcohols were present in smaller quantities from 1.5% (C14:0) to 11.9% (C22:0) and two alcohols were present in traces (C26:0 and C28:0). Only two alcohols (C18:0 and C20:0) were detected in comparable amounts in internal lipids of female (3.61±0.32 and 5.01±0.42 µg/g of the insect body, respectively). For isolated alcohols antimicrobial activity against reference strains of bacteria and fungi was determined (Bacillus subtilis ATCC 6633, Rhodococcus equi ATCC 6939, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 13882, Proteus vulgaris ATCC 13315, Aspergillus niger ATCC, Candida albicans ATCC 10231, Candida lipolytica PCM 2680, and Candida tropicalis PCM 2681). Individual alcohols have shown approximately equal activity against fungal strains. C14:0 was effective against gram-positive bacteria, while gram-negative bacteria were resistant to all tested alcohols. Mixtures of alcohols found in cuticular lipids of larvae, pupae, male and female of M. domestica presented in general higher antimicrobial activity in comparison to individual alcohols. In contrast, crude extracts containing both, cuticular and internal lipids, showed no antifungal activity against entomopathogenic fungus C. coronatus efficiently killing adult house flies (but not larvae and pupae).
Pressure and particle motion detection thresholds in fish: a re-examination of salient auditory cues in teleosts
Authors: Radford Craig A , Montgomery John C , Caiger Paul , Higgs Dennis M
Published: June 2012

The auditory evoked potential technique has been used for the past 30 years to evaluate the hearing ability of fish. The resulting audiograms are typically presented in terms of sound pressure (dB re 1 µPa) with the particle motion (dB re 1 ms-2) component largely ignored until recently. When audiograms have been presented in terms of particle acceleration, one of two approaches has been used for stimulus characterization: measuring the pressure gradient between two hydrophones or using accelerometers. With rare exceptions these values are presented from experiments using a speaker as the stimulus, thus making it impossible to truly separate the contribution of direct particle displacement and pressure detection in the response. Here we compare the particle acceleration and pressure auditory thresholds of three species of fish with differing hearing specialisations, Goldfish (Carassius auratus; weberian ossicles), bigeye (Pempheris adspersus hearing specialisation) and a third species with no swim bladder, the common triplefin (Forstergyian lappillum), using three different methods of determining particle accelerations. In terms of particle acceleration all three fish species have similar hearing thresholds, but when expressed as pressure thresholds goldfish are the most sensitive followed by bigeye, with triplefin the least sensitive. It is suggested here that all fish have a similar ability to detect the particle motion component of the sound field and it is their ability to transduce the pressure component of the sound field to the inner ear via ancillary hearing structures that provides the differences in hearing ability. Therefore, care is needed in stimuli presentation and measurement when determining hearing ability of fish and when interpreting comparative hearing abilities between species.
miR-200c is aberrantly expressed in leiomyomas in an ethnic-dependent manner and targets ZEBs, VEGFA, TIMP2, and FBLN5
Authors: Chuang Tsai-Der , Panda Harekrushna , Luo Xiaoping , Chegini Nasser
Published: June 2012

MicroRNA-200c (miR-200c) through repression of specific target genes has been associated with cellular transition, tumorigenesis, and tissue fibrosis. We explored the expression and functional aspects of miR-200c in genesis of leiomyomas (LYO), benign uterine tumors with fibrotic characteristic. Using LYO and matched myometrium (MYO;n=76) from untreated and from patients exposed to hormonal therapies (GNRH agonist (GNRHa), Depo-Provera, and oral contraceptives), we found that miR-200c was expressed at significantly lower levels (P<0.05) in LYO as compared with MYO. These levels were lower in LYO from African Americans as compared with Caucasians, patients experiencing abnormal uterine bleeding and those exposed to GNRHa therapy. Gain-of-function of miR-200c in isolated leiomyoma smooth muscle cells (LSMCs), myometrial smooth muscle cells (MSMCs), and leiomyosarcoma cell line (SKLM-S1) repressedZEB1/ZEB2mRNAs and proteins, with concurrent increase in E-cadherin (CDH1) and reduction in vimentin expression, phenotypic alteration, and inhibition of MSMC and LSMC proliferations. We further validatedTIMP2, FBLN5, andVEGFAas direct targets of miR-200c through interaction with their respective 3′ UTRs, and other genes as determined by microarray analysis. At tissue levels, LYO expressed lower levels ofTIMP2andFBLN5mRNAs but increased protein expressions, which to some extent altered due to hormonal exposure. Given the regulatory functions ofZEBs, VEGFA, FBLN5, andTIMP2on cellular activities that promote cellular transition, angiogenesis, and matrix remodeling, we concluded that altered expression of miR-200c may have a significant impact on the outcome of LYO growth, maintenance of their mesenchymal and fibrotic characteristics, and possibly their associated symptoms.
GLP1 and cancer: friend or foe?
Authors: Vangoitsenhoven Roman , Mathieu Chantal , Van der Schueren Bart
Published: June 2012

The new incretin-based therapies, dipeptidyl peptidase-4 (DPP4) inhibitors and glucagon like peptide 1 (GLP1) receptor agonists are widely used for the treatment of type 2 diabetes because of their glucose-lowering capacity with low risk of hypoglycemia. As they are weight neutral or induce weight loss in this mostly overweight population, they are popular among clinicians and patients alike. Nonetheless, concerns have been raised about GLP1's trophic effects. While increased β cell mass observed in rodents sounds appealing for treatment of diabetes, there was also an increased incidence of medullary thyroid cancer (MTC) in some species. We reviewed literature available in the Medline database until March 2012. Safety signals have emerged for MTC and pancreatic carcinoma from adverse event databases in the United States and Europe. Considering the relatively short duration of these studies, it is more likely that premalignant lesions are stimulated in presence of GLP1, rather than new neoplasms induced. Moreover, interpreting results of animal studies is difficult because of species-specific differences in presence and density of GLP1 receptors. Furthermore, data are emerging suggesting beneficial effects of GLP1 on colon and breast cancer. In conclusion, presently, the benefits of using DPP4 inhibitors or GLP1 receptor agonists for treatment of type 2 diabetes outweigh the risks. Nonetheless, their safety profile should be monitored and their indications should be widened cautiously. At present they remain contra-indicated in patients with a personal or family history of MTC or multiple endocrine neoplasia type 2.
Stimulation of MC38 tumor growth by insulin analog X10 involves the serine synthesis pathway
Authors: Hvid Henning , Fendt Sarah-Maria , Blouin Marie-José , Birman Elena , Voisin Gregory , Svendsen Angela Manegold , Frank Russell , Vander Heiden Matthew G , Stephanopoulos Gregory , Hansen Bo Falck , Pollak Michael
Published: June 2012

Recent evidence suggests that type II diabetes is associated with increased risk and/or aggressive behavior of several cancers, including those arising from the colon. Concerns have been raised that endogenous hyperinsulinemia and/or exogenous insulin and insulin analogs might stimulate proliferation of neoplastic cells. However, the mechanisms underlying possible growth-promoting effects of insulin and insulin analogs in cancer cellsin vivo, such as changes in gene expression, are incompletely described. We observed that administration of the insulin analog X10 significantly increased tumor growth and proliferation in a murine colon cancer model (MC38 cell allografts). Insulin and X10 altered gene expression in MC38 tumors in a similar fashion, but X10 was more potent in terms of the number of genes influenced and the magnitude of changes in gene expression. Many of the affected genes were annotated to metabolism, nutrient uptake, and protein synthesis. Strikingly, expression of genes encoding enzymes in the serine synthesis pathway, recently shown to be critical for neoplastic proliferation, was increased following treatment with insulin and X10. Using stable isotopic tracers and mass spectrometry, we confirmed that insulin and X10 increased glucose contribution to serine synthesis in MC38 cells. The data demonstrate that the tumor growth-promoting effects of insulin and X10 are associated with changes in expression of genes involved in cellular energy metabolism and reveal previously unrecognized effects of insulin and X10 on serine synthesis.