bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel linkage map of sugarcane with evidence for clustering of retrotransposon-based markers
Authors: Palhares Alessandra C , Rodrigues-Morais Taislene B , Van Sluys Marie-Anne , Domingues Douglas S , Maccheroni Walter , Jordão Hamilton , Souza Anete P , Marconi Thiago G , Mollinari Marcelo , Gazaffi Rodrigo , Garcia Antonio Augusto F , Vieira Maria Lucia Carneiro
Published: June 2012

Background

The development of sugarcane as a sustainable crop has unlimited applications. The crop is one of the most economically viable for renewable energy production, and CO2 balance. Linkage maps are valuable tools for understanding genetic and genomic organization, particularly in sugarcane due to its complex polyploid genome of multispecific origins. The overall objective of our study was to construct a novel sugarcane linkage map, compiling AFLP and EST-SSR markers, and to generate data on the distribution of markers anchored to sequences of scIvana_1, a complete sugarcane transposable element, and member of the Copia superfamily.

Results

The mapping population parents (‘IAC66-6’ and ‘TUC71-7’) contributed equally to polymorphisms, independent of marker type, and generated markers that were distributed into nearly the same number of co-segregation groups (or CGs). Bi-parentally inherited alleles provided the integration of 19 CGs. The marker number per CG ranged from two to 39. The total map length was 4,843.19 cM, with a marker density of 8.87 cM. Markers were assembled into 92 CGs that ranged in length from 1.14 to 404.72 cM, with an estimated average length of 52.64 cM. The greatest distance between two adjacent markers was 48.25 cM. The scIvana_1-based markers (56) were positioned on 21 CGs, but were not regularly distributed. Interestingly, the distance between adjacent scIvana_1-based markers was less than 5 cM, and was observed on five CGs, suggesting a clustered organization.

Conclusions

Results indicated the use of a NBS-profiling technique was efficient to develop retrotransposon-based markers in sugarcane. The simultaneous maximum-likelihood estimates of linkage and linkage phase based strategies confirmed the suitability of its approach to estimate linkage, and construct the linkage map. Interestingly, using our genetic data it was possible to calculate the number of retrotransposon scIvana_1 (~60) copies in the sugarcane genome, confirming previously reported molecular results. In addition, this research possibly will have indirect implications in crop economics e.g., productivity enhancement via QTL studies, as the mapping population parents differ in response to an important fungal disease.
Depletion of the non-coding regulatory 6S RNA in E. coli causes a surprising reduction in the expression of the translation machinery
Authors: Neusser Thomas , Polen Tino , Geissen René , Wagner Rolf
Published: June 2012

Background

6S RNA from E. coli is known to bind to RNA polymerase interfering with transcription initiation. Because 6S RNA concentrations are maximal at stationary phase and binding occurs preferentially to the holoenzyme associated with σ70 (Eσ70) it is believed that 6S RNA supports adjustment to stationary phase transcription. Previous studies have also suggested that inhibition is specific for σ70-dependent promoters characterized by a weak -35 recognition motif or extended -10 promoters. There are many exceptions to this precept, showing that other types of promoters, including stationary phase-specific (σ38-dependent) promoters are inhibited.

Results

To solve this apparent ambiguity and to better understand the role of 6S RNA in stationary phase transition we have performed a genome-wide transcriptional analysis of wild-type and 6S RNA deficient cells growing to mid-log or early stationary phase. We found 245 genes at the exponential growth phase and 273 genes at the early stationary phase to be ≥ 1.5-fold differentially expressed. Up- and down-regulated genes include many transcriptional regulators, stress-related proteins, transporters and several enzymes involved in purine metabolism. As the most striking result during stationary phase, however, we obtained in the 6S RNA deficient strain a concerted expression reduction of genes constituting the translational apparatus. In accordance, primer extension analysis showed that transcription of ribosomal RNAs, representing the key molecules for ribosome biogenesis, is also significantly reduced under the same conditions. Consistent with this finding biochemical analysis of the 6S RNA deficient strain indicates that the lack of 6S RNA is apparently compensated by an increase of the basal ppGpp concentration, known to affect growth adaptation and ribosome biogenesis.

Conclusions

The analysis demonstrated that the effect of 6S RNA on transcription is not strictly confined to σ70-dependent promoters. Moreover, the results indicate that 6S RNA is embedded in stationary phase adaptation, which is governed by the capacity of the translational machinery.
The first wave of pandemic influenza (H1N1) 2009 in Germany: From initiation to acceleration
Authors: Poggensee Gabriele , Gilsdorf Andreas , Buda Silke , Eckmanns Tim , Claus Hermann , Altmann Doris ,   RKI Working Group Pandemic Influenza, Krause Gérard , Haas Walter
Published: June 2012

Background

The first imported case of pandemic influenza (H1N1) 2009 in Germany was confirmed in April 2009. However, the first wave with measurable burden of disease started only in October 2009. The basic epidemiological and clinical characteristics of the pandemic were analysed in order to understand the course of the pandemic in Germany.

Methods

The analysis was based on data from the case-based, mandatory German surveillance system for infectious diseases. Cases notified between 27 April and 11 November 2009 and fulfilling the case definition were included in the study.

Results

Two time periods with distinct epidemiologic characteristics could be determined: 23,789 cases (44.1%) occurred during the initiation period (IP, week 18 to 41), and 30,179 (55.9%) during the acceleration period (AP, week 42 to 45). During IP, coinciding with school summer holidays, 61.1% of cases were travel-related and one death occurred. Strict containment efforts were performed until week 32. During AP the majority of cases (94.3%) was autochthonous, 12 deaths were reported. The main affected age group shifted from 15 to 19 years in IP to 10 to 14 years in AP (median age 19 versus 15 years; p < 0.001). The proportion of cases with underlying medical conditions increased from 4.7% to 6.9% (p < 0.001). Irrespective of the period, these cases were more likely to be hospitalised (OR = 3.6 [95% CI: 3.1; 4.3]) and to develop pneumonia (OR = 8.1 [95% CI: 6.1; 10.7]). Furthermore, young children (0 to 2 years) (OR = 2.8 [95% CI: 1.5; 5.2]) and persons with influenza-like illness (ILI, OR = 1.4 [95% CI: 1.0; 2.1]) had a higher risk to develop pneumonia compared to other age groups and individuals without ILI.

Conclusion

The epidemiological differences we could show between summer and autumn 2009 might have been influenced by the school summer holidays and containment efforts. The spread of disease did not result in change of risk groups or severity. Our results show that analyses of case-based information can advise future public health measures.
Seroprevalence of Human Papillomavirus Types 6, 11, 16 and 18 in Chinese Women
Authors: Ji Jia , Sun Hai-Kui , Smith Jennifer S , Wang He , Esser Mark T , Hu Shangying , Pretorius Robert G , Chen Wen , Belinson Jerome L , Qiao You-Lin
Published: June 2012

Background

Human papillomavirus (HPV) seroprevalence data have not previously been reported for different geographical regions of China. This study investigated the cross-sectional seroprevalence of antibodies to HPV 6, 11, 16, and 18 virus-like particles in Chinese women.

Methods

Population-based samples of women were enrolled from 2006 to 2007 in 3 rural and 2 urban areas of China. Each consenting woman completed a questionnaire and provided a blood sample. Serum antibodies were detected using a competitive Luminex immunoassay that measures antibodies to type-specific, neutralizing epitopes on the virus-like particles.

Results

A total of 4,731 women (median age 35, age range 14-54) were included, of which 4,211 were sexually active women (median age 37) and 520 virgins (median age 18). Low risk HPV 6 was the most common serotype detected (7.3%), followed by HPV 16 (5.6%), HPV 11 (2.9%), and HPV 18 (1.9%). Overall HPV seroprevalence to any type was significantly higher among sexually active women (15.8%) than virgins (2.5%) (P = 0.005). Overall seroprevalence among sexually active women gradually increased with age. Women from rural regions had significantly lower overall seroprevalence (Odds Ratio (OR) = 0.7; 95% CI: 0.6-0.9, versus metropolitan regions, P < 0.001). With increasing number of sexual partners, women were at higher risk of seropositivity of any type (OR = 2.6; 95% CI: 1.7-3.9 for > = 4 partners versus 1 partner, P < 0.001). Wives were at higher risk of seropositivity for HPV 16/18/6/11 when reporting having a husband who had an extramarital sexual relationship (OR = 2.0; 95% CI: 1.6-2.5, versus those whose husbands having no such relationship, P < 0.001). There was a strong association between HPV 16 seropositivity and presence of high-grade cervical lesions (OR = 6.5; 95% CI: 3.7-11.4, versus normal cervix, P < 0.001).

Conclusions

HPV seroprevalence differed significantly by age, geography, and sexual behavior within China, which all should be considered when implementing an optimal prophylactic HPV vaccination program in China.
Quality of guidelines on the management of diabetes in pregnancy: a systematic review
Authors: Greuter Marjolein JE , van Emmerik Nathalie MA , Wouters Maurice GAJ , van Tulder Maurits W
Published: June 2012

Background

Diabetes during pregnancy can lead to severe risks for both mother and fetus when it is not managed properly. The use of rigorously developed guidelines with a robust implementation process can have a positive influence on the management of diabetes during pregnancy. This study aims to compare recommendations and assess the quality of clinical guidelines on gestational diabetes mellitus (GDM) and pre-existing diabetes mellitus during pregnancy.

Methods

Guidelines were selected by searching PubMed, the Guideline Clearing House and Google. All guidelines developed since 2000 on diabetes during pregnancy in English or Dutch were considered. Recommendations of the guidelines were compared. Furthermore, the quality was assessed by two authors independently, using the AGREE instrument.

Results

Eight guidelines were included. According to the AGREE instrument, the quality of most guidelines was low. The domains editorial independence, stakeholder involvement and rigour of development had the lowest scores. Recommendations were mainly comparable on glycemic control, preconceptional counseling and prenatal care and labour. Differences between recommendations were found for screening on GDM and induction of labour.

Conclusions

The quality of most guidelines concerning the management of diabetes during pregnancy needs to be improved. A more systematic approach in the development of these guidelines, more attention for updating procedures and piloting of the guidelines and involvement of target users and patients is recommended.
On residents’ satisfaction with community health services after health care system reform in Shanghai, China, 2011
Authors: Li Zhijian , Hou Jiale , Lu Lin , Tang Shenglan , Ma Jin
Published: June 2012

Background

Health care system reform is a major issue in many countries and therefore how to evaluate the effects of changes is incredibly important. This study measured residents’ satisfaction with community health care service in Shanghai, China, and aimed to evaluate the effect of recent health care system reform.

Methods

Face-to-face interviews were performed with a stratified random sample of 2212 residents of the Shanghai residents using structured questionnaires. In addition, 972 valid responses were retrieved from internet contact. Controlling for sex, age, income and education, the study used logistic regression modeling to analyze factors associated with satisfaction and to explain the factors that affect the residents’ satisfaction.

Results

Comparing current attitudes with those held at the initial implementation of the reform in this investigation, four dimensions of health care were analyzed: 1) the health insurance system; 2) essential drugs; 3) basic clinical services; and 4) public health services. Satisfaction across all dimensions improved since the reform was initiated, but differences of satisfaction level were found among most dimensions and groups. Residents currently expressed greater satisfaction with clinical service (average score=3.79, with 5 being most satisfied) and the public health/preventive services (average score=3.62); but less satisfied with the provision of essential drugs (average score=3.20) and health insurance schemes (average score=3.23). The disadvantaged groups (the elderly, the retired, those with only an elementary education, those with lower incomes) had overall poorer satisfaction levels on these four aspects of health care (P<0.01). 25.39% of the respondents thought that their financial burden had increased and 38.49% thought that drugs had become more expensive.

Conclusion

The respondents showed more satisfaction with the clinical services (average score=3.79) and public health services/interventions (average score=3.79); and less satisfaction with the health insurance system (average score=3.23) and the essential drug system (average score=3.20). Disadvantaged groups showed lower satisfaction levels overall relative to non-disadvantaged groups.
The plant coumarins auraptene and lacinartin as potential multifunctional therapeutic agents for treating periodontal disease
Authors: Marquis Annie , Genovese Salvatore , Epifano Francesco , Grenier Daniel
Published: June 2012

Background

Periodontal diseases are bacterial infections leading to chronic inflammation disorders that are frequently observed in adults. In the present study, we evaluated the effect of auraptene and lacinartin, two natural oxyprenylated coumarins, on the growth, adherence properties, and collagenase activity of Porphyromonas gingivalis. We also investigated the capacity of these compounds to reduce cytokine and matrix metalloproteinase (MMP) secretion by lipopolysaccharide (LPS)-stimulated macrophages and to inhibit MMP-9 activity.

Methods

Microplate dilution assays were performed to determine the effect of auraptene and lacinartin on P. gingivalis growth as well as biofilm formation stained with crystal violet. Adhesion of FITC-labeled P. gingivalis to oral epithelial cells was monitored by fluorometry. The effects of auraptene and lacinartin on LPS-induced cytokine and MMP secretion by macrophages were determined by immunological assays. Fluorogenic assays were used to evaluate the capacity of the two coumarins to inhibit the activity of P. gingivalis collagenase and MMP-9.

Results

Only lacinartin completely inhibited P. gingivalis growth in a complex culture medium. However, under iron-limiting conditions, auraptene and lacinartin both inhibited the growth of P. gingivalis. Lacinartin also inhibited biofilm formation by P. gingivalis and promoted biofilm desorption. Both compounds prevented the adherence of P. gingivalis to oral epithelial cells, dose-dependently reduced the secretion of cytokines (IL-8 and TNF-α) and MMP-8 and MMP-9 by LPS-stimulated macrophages, and inhibited MMP-9 activity. Lacinartin also inhibited P. gingivalis collagenase activity.

Conclusions

By acting on multiple targets, including pathogenic bacteria, tissue-destructive enzymes, and the host inflammatory response, auraptene and lacinartin may be promising natural compounds for preventing and treating periodontal diseases.
Impairment of the cell-to-matrix adhesion and cytotoxicity induced by the Mediterranean jellyfish Pelagia noctiluca venom and its fractions in cultured glioblastoma cells
Authors: Ayed Yosra , Bousabbeh Manel , Mabrouk Hazem Ben , Morjen Maram , Marrakchi Naziha , Bacha Hassen
Published: June 2012

Background

The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited source of new active substances in the field of the development of bioactive products. In our study, we have investigated the efficiency of the venom from the Mediterranean jellyfish, Pelagia noctiluca and its fractions for anti-proliferative and anti-cell adhesion to cell–extracellular matrix activities.

Results

Our experiments have indicated that the separation of the Mediterranean jellyfish Pelagia noctiluca crude venom extract by sephadex G-75 chromatography led to four fractions (F1, F2, F3, and F4). Among the four fractions F1 and F3 were cytotoxic against U87 cells with IC50 values of 125 and 179 μg/ml respectively. The venom, F1, F2 and F 3 showed significant anti-proliferative activity in time-dependent manner. Our results also suggest that these fractions and the venom are able to inhibit cell adhesion to fibrinogen in dose-dependent manner. This inhibition is reliant on its ability to interact with integrins.

Conclusions

To conclude, we have demonstrated for the first time that Pelagia noctiluca venom and its fractions especially (F1 and F2) display potent anti-tumoral properties. Separation by sephadex G-75 chromatography give rise to more active fractions than the crude venom extract. The purification and the determination of chemical structures of compounds of these active fractions are under investigation. Overall, Pelagia noctiluca venom may has the potential to serve as a template for future anticancer-drug development.
Epigenetic functions enriched in transcription factors binding to mouse recombination hotspots
Authors: Wu Min , Kwoh Chee-Keong , Przytycka Teresa M , Li Jing , Zheng Jie
Published: June 2012

The regulatory mechanism of recombination is a fundamental problem in genomics, with wide applications in genome-wide association studies, birth-defect diseases, molecular evolution, cancer research, etc. In mammalian genomes, recombination events cluster into short genomic regions called "recombination hotspots". Recently, a 13-mer motif enriched in hotspots is identified as a candidate cis-regulatory element of human recombination hotspots; moreover, a zinc finger protein, PRDM9, binds to this motif and is associated with variation of recombination phenotype in human and mouse genomes, thus is a trans-acting regulator of recombination hotspots. However, this pair of cis and trans-regulators covers only a fraction of hotspots, thus other regulators of recombination hotspots remain to be discovered. In this paper, we propose an approach to predicting additional trans-regulators from DNA-binding proteins by comparing their enrichment of binding sites in hotspots. Applying this approach on newly mapped mouse hotspots genome-wide, we confirmed that PRDM9 is a major trans-regulator of hotspots. In addition, a list of top candidate trans-regulators of mouse hotspots is reported. Using GO analysis we observed that the top genes are enriched with function of histone modification, highlighting the epigenetic regulatory mechanisms of recombination hotspots.
Identifying transcription factors and microRNAs as key regulators of pathways using Bayesian inference on known pathway structures
Authors: Roqueiro Damian , Huang Lei , Dai Yang
Published: June 2012

Background

Transcription factors and microRNAs act in concert to regulate gene expression in eukaryotes. Numerous computational methods based on sequence information are available for the prediction of target genes of transcription factors and microRNAs. Although these methods provide a static snapshot of how genes may be regulated, they are not effective for the identification of condition-specific regulators.

Results

We propose a new method that combines: a) transcription factors and microRNAs that are predicted to target genes in pathways, with b) microarray expression profiles of microRNAs and mRNAs, in conjunction with c) the known structure of molecular pathways. These elements are integrated into a Bayesian network derived from each pathway that, through probability inference, allows for the prediction of the key regulators in the pathway. We demonstrate 1) the steps to discretize the expression data for the computation of conditional probabilities in a Bayesian network, 2) the procedure to construct a Bayesian network using the structure of a known pathway and the transcription factors and microRNAs predicted to target genes in that pathway, and 3) the inference results as potential regulators of three signaling pathways using microarray expression profiles of microRNA and mRNA in estrogen receptor positive and estrogen receptor negative tumors.

Conclusions

We displayed the ability of our framework to integrate multiple sets of microRNA and mRNA expression data, from two phenotypes, with curated molecular pathway structures by creating Bayesian networks. Moreover, by performing inference on the network using known evidence, e.g., status of differentially expressed genes, or by entering hypotheses to be tested, we obtain a list of potential regulators of the pathways. This, in turn, will help increase our understanding about the regulatory mechanisms relevant to the two phenotypes.
Predicting synthetic lethal genetic interactions in Saccharomyces cerevisiae using short polypeptide clusters
Authors: Zhang Yuehua , Li Bo , Srimani Pradip K , Chen Xuewen , Luo Feng
Published: June 2012

Background

Protein synthetic lethal genetic interactions are useful to define functional relationships between proteins and pathways. However, the molecular mechanism of synthetic lethal genetic interactions remains unclear.

Results

In this study we used the clusters of short polypeptide sequences, which are typically shorter than the classically defined protein domains, to characterize the functionalities of proteins. We developed a framework to identify significant short polypeptide clusters from yeast protein sequences, and then used these short polypeptide clusters as features to predict yeast synthetic lethal genetic interactions. The short polypeptide clusters based approach provides much higher coverage for predicting yeast synthetic lethal genetic interactions. Evaluation using experimental data sets showed that the short polypeptide clusters based approach is superior to the previous protein domain based one.

Conclusion

We were able to achieve higher performance in yeast synthetic lethal genetic interactions prediction using short polypeptide clusters as features. Our study suggests that the short polypeptide cluster may help better understand the functionalities of proteins.
Leiomyosarcoma of the inferior vena cava level II involvement: curative resection and reconstruction of renal veins
Authors: Wang Quan , Jiang Jing , Wang Chao , Lian Guodong , Jin Mei-Shan , Cao Xueyuan
Published: June 2012

Leiomyosarcoma of the inferior vena cava (IVCL) is a rare retroperitoneal tumor. We report two cases of level II (middle level, renal veins to hepatic veins) IVCL, who underwent en bloc resection with reconstruction of bilateral or left renal venous return using prosthetic grafts. In our cases, IVCL is documented to be occluded preoperatively, therefore, radical resection of tumor and/or right kidney was performed and the distal end of inferior vena cava was resected and without caval reconstruction. None of the patients developed edema or acute renal failure postoperatively. After surgical resection, adjuvant radiation therapy was administrated. The patients have been free of recurrence 2 years and 3 months, 9 months after surgery, respectively, indicating the complete surgical resection and radiotherapy contribute to the better survival. The reconstruction of inferior vena cava was not considered mandatory in level II IVCL, if the retroperitoneal venous collateral pathways have been established. In addition to the curative resection of IVCL, the renal vascular reconstruction minimized the risks of procedure-related acute renal failure, and was more physiologically preferable. This concept was reflected in the treatment of the two patients reported on.
Diffusion-weighted imaging and FDG PET/CT: predicting the prognoses with apparent diffusion coefficient values and maximum standardized uptake values in patients with invasive ductal carcinoma
Authors: Choi Bo Bae , Kim Sung Hun , Kang Bong Joo , Lee Ji Hye , Song Byung Joo , Jeong Seung Hee , Yim Hyeon Woo
Published: June 2012

Background

FDG PET/CT and DWI are both functional modalities that indirectly represent the biological characteristics of cancer, but there are few studies exploring the association between the two modalities and prognostic factors. Our study attempted to evaluate the mutual association by comparing the prognostic factors, SUVmax value of PET/CT, and ADC values associated with diffusion imaging in invasive ductal carcinoma (IDC) patients.

Methods

Patients with pathologically confirmed IDC were recruited. There were 118 patients who underwent MRI, including DWI, FDG PET/CT, and immunohistochemical staining of the surgical specimen. Histologic analysis was done on tumor size, lymph node metastasis, expression of estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, and epidermal growth factor receptors (EGFR). The relationship among ADC values, SUVmax and prognostic factors were evaluated.

Results

There was significant association between the ADC value and ER-positive and HER2-negative expression. Significant associations were noted between SUVmax and tumor size, lymph node metastasis, histologic grade, ER and PR expression, EGFR and Ki-67. However, there was no significant correlation between the ADC value and SUVmax.

Conclusions

Even though there was no correlation between ADC and SUVmax, both indexes are useful for predicting the prognosis of IDC.
Tumor-derived hepatocyte growth factor is associated with poor prognosis of patients with glioma and influences the chemosensitivity of glioma cell line to cisplatin in vitro
Authors: Guo You-feng , Wang Xiao-bing , Tian Xiao-ying , Li Yang , Li Bin , Huang Quan , Zhang Meng , Li Zhi
Published: June 2012

Background

We examined the association of tumor-derived hepatocyte growth factor (HGF) with the clinicopathological features of gliomas and investigated the effect of HGF inhibition on the biological behavior of tumor cells in vitro in order to determine whether HGF is a valuable prognostic predictor for glioma patients.

Methods

Seventy-six cases of glioma were collected. The tumor-derived HGF expression, cell proliferation index (PI) and intratumoral microvessels were evaluated by immunohistochemistry. Correlation between immunostaining and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. U87MG glioma cells were transfected with short interference (si)-RNA for HGF, and the cell viability, migratory ability and chemosensitivity to cisplatin were evaluated in vitro.

Results

Both high HGF expression in tumor cells (59.2%, 45/76) and high PI were significantly associated with high-grade glioma and increased microvessels in tumors (P < 0.05). However, only histological grading (P = 0.004) and high-expression of HGF (P = 0.008) emerged as independent prognostic factors for the overall survival of glioma patients. The tumor-derived HGF mRNA and protein expressions were significantly decreased in vitro after transfection of HGF siRNA. HGF siRNA inhibited the cell growth and reduced cell migratory ability. Moreover, HGF siRNA transfection enhanced the chemosensitivity of U87MG glioma cells to cisplatin.

Conclusion

This study indicated that there was significant correlation among tumor cell-derived HGF, cell proliferation and microvessel proliferation in gliomas. HGF might influence tumor progression by modulating the cell growth, migration and chemoresistance to drugs. Increased expression of HGF may be a valuable predictor for prognostic evaluation of glioma patients.
The existence of solutions for nonlinear fractional multipoint boundary value problems at resonance
Authors: Xu Na , Liu Wenbin , Xiao Lishun
Published: June 2012

A class of nonlinear fractional multipoint boundary value problems at resonance is considered in this article. The existence results are obtained by the method of the coincidence degree theory of Mawhin. An example is given to illustrate the results.

MSC:34A08.
Evaluating the role of IL-11, a novel cytokine in the IL-6 family, in a mouse model of spinal cord injury
Authors: Cho Newton , Nguyen Dung H , Satkunendrarajah Kajana , Branch Donald R , Fehlings Michael G
Published: June 2012

Background

Spinal cord injury (SCI) is a devastating condition with substantial functional and social morbidity. Previous research has established that the neuroinflammatory response plays a significant role in cord damage post-SCI. However, global immunosuppressive therapies have demonstrated mixed results. As a result, more specific therapies modulating inflammation after injury are needed. In this regard, research into cytokine signaling has demonstrated that cytokines of the gp130 family including IL-6 and leukemia inhibitory factor (LIF) play key roles in mediating damage to the spinal cord. Since members of the gp130 family all share a common signal transduction pathway via the JAK/STAT system, we performed the first study of a relatively new member of the gp130 family, IL-11, in SCI.

Methods

A validated clip-compression mouse model of SCI was used to assess for temporal changes in expression of IL-11 and its receptor, IL-11Rα, post-SCI. To elucidate the role of IL-II in the pathophysiology of SCI, we compared differences in locomotor recovery (Basso Mouse Score; CatWalk), electrophysiological spinal cord signaling, histopathology, and the acute inflammatory neutrophil response in IL-11Rα knockouts with littermate wild-type C57BL/6 mice.

Results

We found an increase in gene expression of IL-11 in the spinal cord to a peak at twenty-four hours post-SCI with increases in IL-11Rα gene expression, peaking at seven days post-SCI. In spite of clear changes in the temporal expression of both IL-11 and its receptor, we found that there were no significant differences in motor function, electrophysiological signaling, histopathology, or neutrophil infiltration into the spinal cord between wild-type and knockout mice.

Conclusions

This is the first study to address IL-11 in SCI. This study provides evidence that IL-11 signaling may not play as significant a role in SCI as other gp130 cytokines, which will ideally guide future therapy design and the signaling pathways those therapies target.
Murine pulmonary responses after sub-chronic exposure to aluminum oxide-based nanowhiskers
Authors: Adamcakova-Dodd Andrea , Stebounova Larissa V , O’Shaughnessy Patrick T , Kim Jong Sung , Grassian Vicki H , Thorne Peter S
Published: June 2012

Background

Aluminum oxide-based nanowhiskers (AO nanowhiskers) have been used in manufacturing processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal and plastic composite materials. They are classified as high aspect ratio nanomaterials. Our aim was to assess in vivo toxicity of inhaled AO nanowhisker aerosols.

Methods

Primary dimensions of AO nanowhiskers specified by manufacturer were 2–4 nm x 2800 nm. The aluminum content found in this nanomaterial was 30% [mixed phase material containing Al(OH)3 and AlOOH]. Male mice (C57Bl/6 J) were exposed to AO nanowhiskers for 4 hrs/day, 5 days/wk for 2 or 4 wks in a dynamic whole body exposure chamber. The whiskers were aerosolized with an acoustical dry aerosol generator that included a grounded metal elutriator and a venturi aspirator to enhance deagglomeration. Average concentration of aerosol in the chamber was 3.3 ± 0.6 mg/m3 and the mobility diameter was 150 ± 1.6 nm. Both groups of mice (2 or 4 wks exposure) were necropsied immediately after the last exposure. Aluminum content in the lung, heart, liver, and spleen was determined. Pulmonary toxicity assessment was performed by evaluation of bronchoalveolar lavage (BAL) fluid (enumeration of total and differential cells, total protein, activity of lactate dehydrogenase [LDH] and cytokines), blood (total and differential cell counts), lung histopathology and pulmonary mechanics.

Results

Following exposure, mean Al content of lungs was 0.25, 8.10 and 15.37 μg/g lung (dry wt) respectively for sham, 2 wk and 4 wk exposure groups. The number of total cells and macrophages in BAL fluid was 2-times higher in animals exposed for 2 wks and 6-times higher in mice exposed for 4 wks, compared to shams (p < 0.01, p < 0.001, respectively). However no neutrophilic inflammation in BAL fluid was found and neutrophils were below 1% in all groups. No significant differences were found in total protein, activity of LDH, or cytokines levels (IL-6, IFN-γ, MIP-1α, TNF-α, and MIP-2) between shams and exposed mice.

Conclusions

Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased lung macrophages, but no inflammatory or toxic responses were observed.
Salvage concurrent radio-chemotherapy for post-operative local recurrence of squamous-cell esophageal cancer
Authors: Zhang Jian , Peng Feng , Li Na , Liu Yongmei , Xu Yong , Zhou Lin , Wang Jin , Zhu Jiang , Huang Meijuan , Gong Youling
Published: June 2012

Purpose

To evaluate the treatment outcome of salvage concurrent radio-chemotherapy for patients with loco-recurrent esophageal cancer after surgery.

Methods

50 patients with loco-recurrent squamous-cell cancer after curative esophagectomy were retrospectively analyzed. Patients were treated with radiotherapy (median 60 Gy) combined with chemotherapy consisting of either 5-fluorouracil (5-FU) plus cisplatin (DDP) (R-FP group) or paclitaxel plus DDP (R-TP group).

Results

The median follow-up period was 16.0 months. The 1-year and 3-year survival rates were 56% and 14%, respectively. The median progression-free survival (PFS) and overall survival (OS) time was 9.8 and 13.3 months respectively. There was no statistical significance of the PFS of the two groups. The OS (median 16.3 months) in the R-TP group was superior to that in the R-FP group (median: 9.8 months) (p = 0.012). Among the patients who had received ≥60 Gy irradiation dose, the median PFS (10.6 months) and OS (16.3 months) were significantly superior to the PFS (8.7 months) and OS (11.3 months) among those patients did not (all p < 0.05). Grade 3 treatment-related gastritis were observed in 6 (27.3%) and 7 (25%) patients in the R-FP and R-TP group respectively. By univariate survival analysis, the age (<60 years), TP regimen and higher irradiation dose might improve the OS of such patients in present study.

Conclusions

For those patients with post-operative loco-recurrent squamous-cell esophageal carcinoma, radiotherapy combined with either FP or TP regimen chemotherapy was an effective salvage treatment. Younger age, treatment with the TP regimen and an irradiation dose ≥60 Gy might improve the patients’ treatment outcome.
Quality of life and depression in caregivers of patients with breast cancer
Authors: Heidari Gorji Mohammad Ali , Bouzar Zinnatossadat , Haghshenas Mohsen , Kasaeeyan Ali Akbar , Sadeghi Mohammad Reza , Ardebil Maryam Didehdar
Published: June 2012

Background

Caregivers have a considerable role in caring and recovery of cancer patients. They may experience psychological problems such as depression, anxiety and decreases in quality of life (QOL). Present study aimed to explore depression and quality of life and their relationship among care givers of patients with breast cancer .

Methods

In this cross sectional study, enrolled 63 care givers of women with breast cancer attending IMKH hospital in Iran as outpatients during 2009–2010. In order to assess the QOL and depression, we used Caregiver QOL Index-Cancer (CQOL-C) and Beck Depression Inventory respectively.

Results

We found depression has strong negative correlation with QOL and participants with depression were more likely to have a poorer overall QOL.

Conclusions

Depression has some effects on QOL of breast cancer patients’ care givers. Assistance and giving information through education and intervention from healthcare professionals is the key of improve the ability of caregivers to enhance their QOL.
Eye findings and immunological markers in probands and their euthyroid relatives from a single family with multiple cases of thyroid autoimmunity
Authors: Ardley Melissa , McCorquodale Thomas , Lahooti Hooshang , Champion Bernard , Wall Jack R
Published: June 2012

Background

Ophthalmopathy is a common manifestation of Graves’ disease (GD) occurring in up to 50% of patients. Mild eye signs are also common in patients with Hashimoto’s thyroiditis. Whilst a genetic predisposition to GD has been demonstrated this is not the case for the ophthalmopathy which often runs a separate course.

Objective

We determined the prevalences of eye and eyelid signs and positive thyroid and orbital antibody tests in first and second degree relatives from a single family with multiple cases of Graves’ disease, ophthalmopathy and Hashimoto’s thyroiditis.

Design

The study cohort comprised 16 subjects from the same family, 4 probands namely, 3 with GD and one with Hashimoto’s thyroiditis and hypothyroidism and 12 of their euthyroid first or second degree relatives. We measured antibodies against calsequestrin (CASQ1) and collagen XIII in an enzyme-linked-immunosorbent assays and TSH-Receptor (TSH-R) antibodies as i) TSH-R binding inhibiting immunoglobulin (TBII) and ii) thyroid stimulating immunoglobulin (TSI). Eye signs were classified and quantified using the clinical activity score (CAS), NOSPECS classes, Nunery types 1 and 2 and the margin-reflex-distance (MRD) as a measure of upper eyelid retraction (UER).

Main outcomes

Whilst significant ophthalmopathy was uncommon in the relatives, mild eye signs, in particular UER, were demonstrated in about a third of them. The presence of eye signs was moderately, but not significantly, associated with the detection of CASQ1 and collagen XIII antibodies, but not TSH-R antibodies.

Conclusion

Our study demonstrates a significant prevalence of positive orbital antibody tests and ophthalmopathy in probands with thyroid autoimmunity and their euthyroid relatives, favouring a role of genetic factors in the development of ophthalmopathy in patients with thyroid autoimmunity.
Lactase persistence, NOD2 status and Mycobacterium avium subsp. paratuberculosis infection associations to Inflammatory Bowel Disease
Authors: Elguezabal Natalia , Chamorro Susana , Molina Elena , Garrido Joseba M , Izeta Ander , Rodrigo Luis , Juste Ramón A
Published: June 2012

Background

Inflammatory Bowel Disease (IBD), which includes both Crohn’s disease (CD) and ulcerative colitis (UC), is caused by a complex interplay involving genetic predisposition, environmental factors and an infectious agent. Mycobacterium avium subsp. paratuberculosis (MAP) is a promising pathogen candidate since it produces a chronic intestinal inflammatory disease in ruminants that resembles CD in humans. MAP is a ubiquitous microorganism, although its presence in the food chain, especially in milk from infected animals, is what made us think that there could be an association between lactase persistence (LP) and IBD. The LCT mutation has brought adaptation to dairy farming which in turn would have increased exposure of the population to infection by MAP. NOD2 gene mutations are highly associated to CD.

Methods

In our study, CD and UC patients and controls from the North of Spain were genotyped for the lactase gene (LCT) and for three NOD-2 variants, R702W, G908R and Cins1007fs. MAP PCR was carried out in order to assess MAP infection status and these results were correlated with LCT and NOD2 genotypes.

Results

As for LP, no association was found with IBD, although UC patients were less likely to present the T/T−13910 variant compared to controls, showing a higher C-allele frequency and a tendency to lactase non-persistence (LNP). NOD2 mutations were associated to CD being the per-allele risk higher for the Cins1007fs variant. MAP infection was more extended among the healthy controls (45.2%) compared to CD patients (21.38%) and UC patients (19.04%) and this was attributed to therapy. The Asturian CD cohort presented higher levels of MAP prevalence (38.6%) compared to the Basque CD cohort (15.5%), differences also attributed to therapy. No interaction was found between MAP infection and LCT or NOD2 status.

Conclusions

We conclude that LP is not significantly associated with IBD, but that MAP infection and NOD2 do show not mutually interacting associations with IBD.
Effect of pretreatments on chemical compositions of mince from Nile tilapia (Oreochromis niloticus) and fishy odor development in protein hydrolysate
Authors: Yarnpakdee Suthasinee , Benjakul Soottawat , Kristinsson Hordur G
Published: June 2012

Fish protein hydrolysates (FPH) have gained increasing attention as nutritious fish products. Lipid oxidation associated with fishy odor in FPH limits its utility. Thus, an appropriate pretreatment of fish mince prior to hydrolysis by lowering pro-oxidants and lipid substrates could tackle such a problem. Different pretreatments of Nile tilapia minces including (1) washing (W), (2) washing and membrane removal (W-MR), and (3) washing/membrane removal followed by acid or alkaline solubilization (W-MR-Ac or W-MR-Al) were conducted prior to hydrolysis. During the hydrolysis process, degree of hydrolysis (DH) and chemical changes were monitored. Color and sensory properties of milk fortified with hydrolysates prepared from mince without and with pretreatment were also determined. Among the pretreated mince samples, W-MR-Al contained the lowest remaining myoglobin and heme iron contents and also showed the lowest total lipid and phospholipid contents (P < 0.05). When mince and W-MR-Al were hydrolyzed using Alcalase for up to 120 min, higher DH were found in W-MR-Al. Furthermore, lower peroxide values, thiobarbituric acid reactive substances, and non-heme iron contents of hydrolysates from W-MR-Al were also observed (P < 0.05). When FPH powder from mince and W-MR-Al (0.3% to 0.5%) were fortified in milk, the former yielded a lower likeness score (P < 0.05) at all levels used. The addition of the latter up to 0.5% had no effect on likeness of all attributes, compared with control (without FPH). An appropriate pretreatment of mince was a promising approach to lower fishy odor problem, caused by lipid oxidation in FPH.
Clinical and microbiological efficacy of continuous versus intermittent application of meropenem in critically ill patients: a randomized open-label controlled trial
Authors: Chytra Ivan , Stepan Martin , Benes Jan , Pelnar Petr , Zidkova Alexandra , Bergerova Tamara , Pradl Richard , Kasal Eduard
Published: June 2012

Introduction

Meropenem bactericidal activity depends on the time when the free drug concentrations remain above the minimum inhibitory concentration of pathogens. The goal of this study was to compare clinical and bacteriological efficacy of continuous meropenem infusion versus bolus administration in critically ill patients with severe infection, and to evaluate the safety of both dosing regimens.

Methods

Patients admitted to the interdisciplinary Intensive Care Unit (ICU) who suffered from severe infections and received meropenem were randomized either in the Infusion group (n = 120) or in the Bolus group (n = 120). Patients in the Infusion group received a loading dose of 2 g of meropenem followed by a continuous infusion of 4 g of meropenem over 24 hours. Patients in the Bolus group were given 2 g of meropenem over 30 minutes every 8 hours. Clinical and microbiological outcome, safety, meropenem-related length of ICU and hospital stay, meropenem-related length of mechanical ventilation, duration of meropenem treatment, total dose of meropenem, and ICU and in-hospital mortality were assessed.

Results

Clinical cure at the end of meropenem therapy was comparable between both groups (83.0% patients in the Infusion vs. 75.0% patients in the Bolus group; P = 0.180). Microbiological success rate was higher in the Infusion group as opposed to the Bolus group (90.6% vs. 78.4%; P = 0.020). Multivariate logistic regression identified continuous administration of meropenem as an independent predictor of microbiological success (OR = 2.977; 95% CI = 1.050 to 8.443; P = 0.040). Meropenem-related ICU stay was shorter in the Infusion group compared to the Bolus group (10 (7 to 14) days vs. 12 (7 to 19) days; P = 0.044) as well as shorter duration of meropenem therapy (7 (6 to 8) days vs. 8 (7 to 10) days; P = 0.035) and lower total dose of meropenem (24 (21 to 32) grams vs. 48 (42 to 60) grams; P < 0.0001). No severe adverse events related to meropenem administration in either group were observed.

Conclusions

Continuous infusion of meropenem is safe and, in comparison with higher intermittent dosage, provides equal clinical outcome, generates superior bacteriological efficacy and offers encouraging alternative of antimicrobial therapy in critically ill patients.
Childhood cognitive function and adult psychopathology:
associations with psychotic and non-psychotic symptoms in the general
population
Authors: Barnett Jennifer H. , McDougall Fiona , Xu Man K. , Croudace Tim J. , Richards Marcus , Jones Peter B.
Published: June 2012

Background

Lower cognitive ability in childhood is associated with increased risk of
future schizophrenia, but its relationship with adult psychotic-like
experiences and other psychopathology is less understood.

Aims

To investigate whether this childhood risk factor is shared with adult
subclinical psychiatric phenotypes including psychotic-like experiences
and general psychiatric morbidity.

Method

A population-based sample of participants born in Great Britain during 1
week in March 1946 was contacted up to 20 times between ages 6 weeks and
53 years. Cognition was assessed at ages 8, 11 and 15 years using a
composite of age-appropriate verbal and non-verbal cognitive tests. At
age 53 years, psychotic-like experiences were self-reported by 2918
participants using four items from the Psychosis Screening Questionnaire
and general psychiatric morbidity was assessed using the scaled version
of the General Health Questionnaire (GHQ-28).

Results

Psychotic-like experiences were reported by 22% of participants, and were
highly comorbid with other psychopathology. Their presence in adults was
significantly associated with poorer childhood cognitive test scores at
ages 8 and 15 years, and marginally so at age 11 years. In contrast, high
GHQ scores were not associated with poorer childhood cognition after
adjustment for the presence of psychotic-like experiences.

Conclusions

Psychotic and non-psychotic psychopathologic symptoms are highly comorbid
in the general population. Lower childhood cognitive ability is a risk
factor for psychotic-like experiences in mid-life; these phenomena may be
one end of a continuum of phenotypic expression driven by variation in
early neurodevelopment.