bluuebunny/crossref_metadata_2025 huggingface dataset:
A hemocyte gene expression signature correlated with predictive capacity of oysters to survive Vibrio infections
Authors: Rosa Rafael Diego , de Lorgeril Julien , Tailliez Patrick , Bruno Roman , Piquemal David , Bachère Evelyne
Published: June 2012

Background

The complex balance between environmental and host factors is an important determinant of susceptibility to infection. Disturbances of this equilibrium may result in multifactorial diseases as illustrated by the summer mortality syndrome, a worldwide and complex phenomenon that affects the oysters, Crassostrea gigas. The summer mortality syndrome reveals a physiological intolerance making this oyster species susceptible to diseases. Exploration of genetic basis governing the oyster resistance or susceptibility to infections is thus a major goal for understanding field mortality events. In this context, we used high-throughput genomic approaches to identify genetic traits that may characterize inherent survival capacities in C. gigas.

Results

Using digital gene expression (DGE), we analyzed the transcriptomes of hemocytes (immunocompetent cells) of oysters able or not able to survive infections by Vibrio species shown to be involved in summer mortalities. Hemocytes were nonlethally collected from oysters before Vibrio experimental infection, and two DGE libraries were generated from individuals that survived or did not survive. Exploration of DGE data and microfluidic qPCR analyses at individual level showed an extraordinary polymorphism in gene expressions, but also a set of hemocyte-expressed genes whose basal mRNA levels discriminate oyster capacity to survive infections by the pathogenic V. splendidus LGP32. Finally, we identified a signature of 14 genes that predicted oyster survival capacity. Their expressions are likely driven by distinct transcriptional regulation processes associated or not associated to gene copy number variation (CNV).

Conclusions

We provide here for the first time in oyster a gene expression survival signature that represents a useful tool for understanding mortality events and for assessing genetic traits of interest for disease resistance selection programs.
Evaluating our ability to predict the structural disruption of RNA by SNPs
Authors: Ritz Justin , Martin Joshua S , Laederach Alain
Published: June 2012

The structure of RiboNucleic Acid (RNA) has the potential to be altered by a Single Nucleotide Polymorphism (SNP). Disease-associated SNPs mapping to non-coding regions of the genome that are transcribed into RiboNucleic Acid (RNA) can potentially affect cellular regulation (and cause disease) by altering the structure of the transcript. We performed a large-scale meta-analysis of Selective 2'-Hydroxyl Acylation analyzed by Primer Extension (SHAPE) data, which probes the structure of RNA. We found that several single point mutations exist that significantly disrupt RNA secondary structure in the five transcripts we analyzed. Thus, every RNA that is transcribed has the potential to be a “RiboSNitch;” where a SNP causes a large conformational change that alters regulatory function. Predicting the SNPs that will have the largest effect on RNA structure remains a contemporary computational challenge. We therefore benchmarked the most popular RNA structure prediction algorithms for their ability to identify mutations that maximally affect structure. We also evaluated metrics for rank ordering the extent of the structural change. Although no single algorithm/metric combination dramatically outperformed the others, small differences in AUC (Area Under the Curve) values reveal that certain approaches do provide better agreement with experiment. The experimental data we analyzed nonetheless show that multiple single point mutations exist in all RNA transcripts that significantly disrupt structure in agreement with the predictions.
Necrosis related HIF-1α expression predicts prognosis in patients with endometrioid endometrial carcinoma
Authors: Seeber Laura MS , Horrée Nicole , van der Groep Petra , van der Wall Elsken , Verheijen René HM , van Diest Paul J
Published: June 2012

Background

Hypoxia inducible factor 1α (HIF-1α) plays an essential role in the adaptive response of cells to hypoxia and is associated with aggressive tumour behaviour. We have shown p27kip1, which is generally reduced in endometrial cancer, to be re-expressed in hypoxic regions. This possibly contributes to survival of cancer cells. The aim of this study was to evaluate the prognostic value of HIF-1α and p27kip expression in patients with endometrioid endometrial cancer.

Methods

Expression levels of HIF-1α, CAIX, Glut-1, and p27kip1 were analyzed by immunohistochemistry. Percentage of positive cells, staining pattern (perinecrotic, diffuse, or mixed) and presence of necrosis were noted.

Results

Necrosis was correlated with shortened disease free survival (DFS) (p = 0.008) and overall survival (OS) (p = 0.045). For DFS, perinecrotic HIF-1α expression was also prognostic (p = 0.044). Moreover, high p27kip1 expression was an additional prognostic factor for these patients with perinecrotic HIF-1α expression. In multivariate Cox regression, perinecrotic HIF-expression emerged as an independent prognostic factor. Perinecrotic HIF-1α expression was significantly associated with CAIX and Glut-1 expression, pointing towards functional HIF-1.

Conclusions

In patients with endometrioid endometrial cancer, necrosis and necrosis-related expression of HIF-1α are important prognostic factors. More aggressive adjuvant treatment might be necessary to improve the outcome of patients with these characteristics.
Predicting neurodevelopmental outcomes for at-risk infants: reliability and predictive validity using a Chinese version of the INFANIB at 3, 7 and 10 months
Authors: Liao Wei , Wen En-yi , Li Chao , Chang Qing , Lv Kui-lin , Yang Wang , He Zhou-mei , Zhao Cong-min
Published: June 2012

Background

Chinese primary care settings have a heavy patient load, shortage of physicians, limited medical resources and low medical literacy, making it difficult to screen for developmental disorders in infants. The Infant Neurological International Battery (INFANIB) for the assessment of neuromotor developmental disorders in infants aged 0 ~ 18 months is widely applied in community health service centers because of its simplicity, time-saving advantages and short learning curve. We aimed to develop and assess a Chinese version of the INFANIB.

Methods

A Chinese version of the INFANIB was developed. Fifty-five preterm and 49 full-term infants with high risk of neurodevelopmental delays were assessed using the Chinese version of the INFANIB at 3, 7 and 10 months after birth. The Peabody Developmental Motor Scale (PDMS) was simultaneously used to assess the children with abnormalities and diagnose cerebral palsy. The sensitivity, specificity, positive predictive value and negative predictive value of the scale were calculated.

Results

At birth, a higher proportion of full-term infants had asphyxia (p < 0.001), brain damage (p = 0.003) and hyperbilirubinemia (p = 0.022). The interclass correlation coefficient and intraclass correlation coefficient values for the INFANIB at 3, 7 and 10 months were >0.8, indicating excellent reliability with regard to inter- and intraobserver differences. The specificity, sensitivity, positive predictive value and negative predictive value were high for both high-risk premature infants and full-term infants at the age of 10 months. For premature infants at the age of 7 months or below, INFANIB had low validity for detecting abnormalities.

Conclusions

The Chinese version of the INFANIB can be useful for screening infants with high-risk for neuromotor abnormality in Chinese primary care settings.
Clinical features of delirious mania: a series of five cases and a brief literature review
Authors: Lee Bo-Shyan , Huang Si-Sheng , Hsu Wen-Yu , Chiu Nan-Ying
Published: June 2012

Background

Little is known about the cause and psychopathology of delirious mania, a type of disorder where delirium and mania occur at the same time. This condition still has no formal diagnostic classification. To provide more information about this potentially life-threatening condition, we studied five patients with delirious mania.

Methods

We describe the cases of five patients with delirious mania admitted to an acute inpatient psychiatric unit between January 2005 and January 2007, and discuss the cases in the context of a selective review of the clinical literature describing the clinical features and treatment of delirious mania.

Results

Two patients had two episodes of delirious mania. Delirium usually resolved faster than mania though not always the case. Delirious mania remitted within seven sessions of the electroconvulsive therapy (ECT).

Conclusions

Delirious mania is a potentially life-threatening but under-recognized neuropsychiatric syndrome. Delirious mania that is ineffectively treated may induce a new-onset manic episode or worsen an ongoing manic episode, and the patient will need prolonged hospitalization. Delirious mania also has a close relationship with catatonia. Early recognition and aggressive treatment, especially with electroconvulsive therapy, can significantly reduce morbidity and mortality.
Burnout, working conditions and gender - results from the northern Sweden MONICA Study
Authors: Norlund Sofia , Reuterwall Christina , Höög Jonas , Lindahl Bernt , Janlert Urban , Birgander Lisbeth Slunga
Published: June 2012

Background

Sick-leave because of mental and behavioural disorders has increased considerably in Sweden since the late nineties, and especially in women. The aim of this study was to assess the level of burnout in the general working population in northern Sweden and analyse it's relation to working conditions and gender.

Methods

In this cross-sectional study the survey from the MONICA-study (Monitoring of Trends and Determinants in Cardiovascular Disease) in northern Sweden 2004 was used. A burnout instrument, the Shirom Melamed Burnout Questionnaire (SMBQ), was incorporated in the original survey which was sent to a random sample of 2500 individuals with a response rate of 76%. After including only actively working people, aged 25-64 years, our study population consisted of 1000 participants (497 women and 503 men). ANOVA and multiple linear regression models were used.

Results

The prevalence of a high level of burnout (SMBQ >4.0) was 13%. Women had a higher level of burnout than men with the most pronounced difference in the age group 35-44 years. In both sexes the level of burnout decreased with age. Demand and control at work, and job insecurity were related to burnout. In women the level of education, socioeconomic position, work object, and working varying hours were of importance. Interaction effects were found between sex and work object, and sex and working hours. In a multiple regression analysis almost half of the gender difference could be explained by work related and life situational factors.

Conclusions

Working life conditions contributed to the level of burnout in this actively working sample from the general population in northern Sweden. Especially in women, socioeconomic position was associated with burnout. The high level of burnout in women compared to men was partly explained by more unfavourable working conditions and life situational factors. Efforts to level out gender differences in burnout should probably focus on improving both working and socioeconomic conditions for women.
Cardiovascular diseases and Type 2 Diabetes in Bangladesh: A systematic review and meta-analysis of studies between 1995 and 2010
Authors: Saquib Nazmus , Saquib Juliann , Ahmed Tahmeed , Khanam Masuma Akter , Cullen Mark R
Published: June 2012

Background

Belief is that chronic disease prevalence is rising in Bangladesh since death from them has increased. We reviewed published cardiovascular (CVD) and Type 2 Diabetes Mellitus (T2DM) studies between 1995 and 2010 and conducted a meta-analysis of disease prevalence.

Methods

A systematic search of CVD and T2DM studies yielded 29 eligible studies (outcome: CVD only = 12, T2DM only = 9, both = 8). Hypertension (HTN) was the primary outcome of CVD studies. HTN and T2DM were defined with objective measures and standard cut-off values. We assessed the study quality based on sampling frame, sample size, and disease evaluation. Random effects models calculated pooled disease prevalence (95% confidence interval) in studies with general population samples (n = 22).

Results

The pooled HTN and T2DM prevalence were 13.7% (12.1%–15.3%) and 6.7% (4.9%–8.6%), respectively. Both diseases exhibited a secular trend by 5-year intervals between 1995 and 2010 (HTN = 11.0%, 12.8%, 15.3%, T2DM = 3.8%, 5.3%, 9.0%). HTN was higher in females (M vs. F: 12.8% vs.16.1%) but T2DM was higher in males (M vs. F: 7.0% vs. 6.2%) (non-significant). Both HTN and T2DM were higher in urban areas (urban vs. rural: 22.2% vs. 14.3% and 10.2% vs. 5.1% respectively) (non-significant). HTN was higher among elderly and among working professionals. Both HTN and T2DM were higher in ‘high- quality’ studies.

Conclusions

There is evidence of a rising secular trend of HTN and T2DM prevalence in Bangladesh. Future research should focus on the evolving root causes, incidence, and prognosis of HTN and T2DM.
Antimicrobial activity of selected South African medicinal plants
Authors: Nielsen Trine R H , Kuete Victor , Jäger Anna K , Meyer Jacobus J Marion , Lall Namrita
Published: June 2012

Background

Nearly 3,000 plant species are used as medicines in South Africa, with approximately 350 species forming the most commonly traded and used medicinal plants. In the present study, twelve South African medicinal plants were selected and tested for their antimicrobial activities against eight microbial species belonging to fungi, Mycobacteria, Gram-positive and Gram-negative bacteria.

Methods

The radiometric respiratory technique using the BACTEC 460 system was used for susceptibility testing against Mycobacterium tuberculosis, and the liquid micro-broth dilution was used for other antimicrobial assays.

Results

The results of the minimal inhibitory concentration (MIC) determinations indicated that the methanol extracts from Acacia karoo, Erythrophleum lasianthum and Salvia africana were able to prevent the growth of all the tested microorganisms. All other samples showed selective activities. MIC values below 100 μg/ml were recorded with A. karoo, C. dentate, E. lasianthum, P. obligun and S. africana on at least one of the nine tested microorganisms. The best activity (MIC value of 39.06 μg/ml) was noted with S. africana against E. coli, S. aureus and M. audouinii, and Knowltonia vesitoria against M. tuberculosis.

Conclusion

The overall results of the present work provide baseline information for the possible use of the studied South African plant extracts in the treatment of microbial infections.
Adherence to medication for the treatment of psychosis: rates and risk factors in an Ethiopian population
Authors: Alene Menna , Wiese Michael D , Angamo Mulugeta T , Bajorek Beata V , Yesuf Elias A , Wabe Nasir Tajure
Published: June 2012

Background

Medication-taking behavior, specifically non-adherence, is significantly associated with treatment outcome and is a major cause of relapse in the treatment of psychotic disorders. Non-adherence can be multifactorial; however, the rates and associated risk factors in an Ethiopian population have not yet been elucidated. The principal aim of this study was to evaluate adherence rates to antipsychotic medications, and secondarily to identify potential factors associated with non-adherence, among psychotic patients at tertiary care teaching hospital in Southwest Ethiopia.

Methods

A cross-sectional study was conducted over a 2-month period in 2009 (January 15thto March 20th) at the Jimma University Specialized Hospital. Adherence was computed using both a compliant fill rate method and self-reporting via a structured patient interview (focusing on how often regular medication doses were missed altogether, and whether they missed taking their doses on time). Data were analyzed using SPSS for windows version 16.0, and chi-square and Pearsons r tests were used to determine the statistical significance of the association of variables with adherence.

Result

Three hundred thirty six patients were included in the study. A total of 75.6% were diagnosed with schizophrenia, while the others were diagnosed with other psychotic disorders. Most (88.1%) patients were taking only antipsychotics, while the remainder took more than one medication. Based upon the compliant fill rate, 57.5% of prescription fills were considered compliant, but only 19.6% of participants had compliant fills for all of their prescriptions. In contrast, on the basis of patients self-report, 52.1% of patients reported that they hadnevermissed a medication dose, 32.0%sometimesmissed their daily doses, 22.0% only missed taking their dose at the specific scheduled time, and 5.9% missedbothtaking their dose at the specific scheduled time andsometimesmissed their daily doses. The most common reasons provided for missing medication doses were: forgetfulness (36.2%); being busy (21.0%); and a lack of sufficient information about the medication (10.0%). Pill burden, medication side-effects, social drug use, and duration of maintenance therapy each had a statistically significant association with medication adherence (P ≤ 0.05).

Conclusion

The observed rate of antipsychotic medication adherence in this study was low, and depending upon the definition used to determine adherence, it is either consistent or low compared to previous reports, which highlights its pervasive and problematic nature. Adherence must therefore be considered when planning treatment strategies with antipsychotic medications, particularly in countries such as Ethiopia.
Artificial neural network aided non-invasive grading evaluation of hepatic fibrosis by duplex ultrasonography
Authors: Zhang Li , LI Qiao-ying , Duan Yun-you , Yan Guo-zhen , Yang Yi-lin , Yang Rui-jing
Published: June 2012

Background

Artificial neural networks (ANNs) are widely studied for evaluating diseases. This paper discusses the intelligence mode of an ANN in grading the diagnosis of liver fibrosis by duplex ultrasonogaphy.

Methods

239 patients who were confirmed as having liver fibrosis or cirrhosis by ultrasound guided liver biopsy were investigated in this study. We quantified ultrasonographic parameters as significant parameters using a data optimization procedure applied to an ANN. 179 patients were typed at random as the training group; 60 additional patients were consequently enrolled as the validating group. Performance of the ANN was evaluated according to accuracy, sensitivity, specificity, Youden’s index and receiver operating characteristic (ROC) analysis.

Results

5 ultrasonographic parameters; i.e., the liver parenchyma, thickness of spleen, hepatic vein (HV) waveform, hepatic artery pulsatile index (HAPI) and HV damping index (HVDI), were enrolled as the input neurons in the ANN model. The sensitivity, specificity and accuracy of the ANN model for quantitative diagnosis of liver fibrosis were 95.0%, 85.0% and 88.3%, respectively. The Youden’s index (YI) was 0.80.

Conclusions

The established ANN model had good sensitivity and specificity in quantitative diagnosis of hepatic fibrosis or liver cirrhosis. Our study suggests that the ANN model based on duplex ultrasound may help non-invasive grading diagnosis of liver fibrosis in clinical practice.
Achieving efficient protein expression in Trichoderma reesei by using strong constitutive promoters
Authors: Li Junxin , Wang Juan , Wang Shaowen , Xing Miao , Yu Shaowen , Liu Gang
Published: June 2012

Backgrounds

The fungus Trichoderma reesei is an important workhorse for expression of homologous or heterologous genes, and the inducible cbh1 promoter is generally used. However, constitutive expression is more preferable in some cases than inducible expression that leads to production of unwanted cellulase components. In this work, constitutive promoters of T. reesei were screened and successfully used for high level homologous expression of xylanase II.

Results

The transcriptional profiles of 13 key genes that participate in glucose metabolism in T. reesei were analyzed by quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR). The results indicated that the mRNA levels of pdc (encoding pyruvate decarboxylase) and eno (encoding enolase) genes were much higher than other genes under high glucose conditions. Recombinant T. reesei strains that homologously expressed xylanase II were constructed by using the promoters of the pdc and eno genes, and they respectively produced 9266 IU/ml and 8866 IU/ml of xylanase activities in the cultivation supernatant in a medium with high glucose concentration. The productivities of xylanase II were 1.61 g/L (with the pdc promoter) and 1.52 g/L (with the eno promoter), approximately accounted for 83% and 82% of the total protein secreted by T. reesei, respectively.

Conclusions

This work demonstrates the screening of constitutive promoters by using RT-qPCR in T. reesei, and has obtained the highest expression of recombinant xylanase II to date by using these promoters.
Parathyroid involvement in thyroid cancer: an unforeseen event
Authors: Chrisoulidou Alexandra , Mandanas Stylianos , Mitsakis Periklis , Iliadou Paschalia K , Manafis Kosmas , Flaris Nikolaos , Boudina Maria , Mathiopoulou Lemonia , Pazaitou-Panayiotou Kalliopi
Published: June 2012

Background

Parathyroid metastatic disease from thyroid cancer has not been studied extensively, mainly due to the need for parathyroid preservation during thyroid surgery.

Methods

We reviewed files from 1,770 patients with thyroid cancer followed up in our department and 10 patients with parathyroid metastases (0.5%) were identified. Patient and tumor characteristics were recorded.

Results

Six out of ten patients had metastases from papillary thyroid cancer, three from follicular thyroid cancer and one from anaplastic thyroid cancer. In nine patients parathyroid infiltration from thyroid cancer was found in direct contact with the thyroid cancer, and in one patient metastatic foci were observed not in continuity with the thyroid cancer.

Conclusions

Parathyroid involvement, although infrequent, may occur in thyroid cancer independently of patient age and tumor size. The clinical significance of such event is not clear. The influence on disease outcome remains to be elucidated.
One-pot synthesis of poly (3,4-ethylenedioxythiophene)-Pt nanoparticle composite and its application to electrochemical H2O2 sensor
Authors: Chang Li-Chi , Wu Huan-Nung , Lin Chia-Yu , Lai Yi-Hsuan , Hu Chih-Wei , Ho Kuo-Chuan
Published: June 2012

Poly(3,4-ethylenedioxythiophene)-Pt nanoparticle composite was synthesized in one-pot fashion using a photo-assisted chemical method, and its electrocatalytic properties toward hydrogen peroxide (H2O2) was investigated. Under UV irradiation, the rates of the oxidative polymerization of EDOT monomer along with the reduction of Pt4+ ions were accelerated. In addition, the morphology of PtNPs was also greatly influenced by the UV irradiation; the size of PtNPs was reduced under UV irradiation, which can be attributed to the faster nucleation rate. The immobilized PtNPs showed excellent electrocatalytic activities towards the electroreduction of hydrogen peroxide. The resultant amperometric sensor showed enhanced sensitivity for the detection of H2O2 as compared to that without PtNPs, i.e., only with a layer of PEDOT. Amperometric determination of H2O2 at −0.55 V gave a limit of detection of 1.6 μM (S / N = 3) and a sensitivity of 19.29 mA cm−2 M−1 up to 6 mM, with a response time (steady state, t95) of 30 to 40 s. Energy dispersive X-ray analysis, transmission electron microscopic image, cyclic voltammetry (CV), and scanning electron microscopic images were utilized to characterize the modified electrode. Sensing properties of the modified electrode were studied both by CV and amperometric analysis.
Synthesis, structure, and photovoltaic property of a nanocrystalline 2H perovskite-type novel sensitizer (CH3CH2NH3)PbI3
Authors: Im Jeong-Hyeok , Chung Jaehoon , Kim Seung-Joo , Park Nam-Gyu
Published: June 2012

A new nanocrystalline sensitizer with the chemical formula (CH3CH2NH3)PbI3 is synthesized by reacting ethylammonium iodide with lead iodide, and its crystal structure and photovoltaic property are investigated. X-ray diffraction analysis confirms orthorhombic crystal phase with a = 8.7419(2) Å, b = 8.14745(10) Å, and c = 30.3096(6) Å, which can be described as 2 H perovskite structure. Ultraviolet photoelectron spectroscopy and UV-visible spectroscopy determine the valence band position at 5.6 eV versus vacuum and the optical bandgap of ca. 2.2 eV. A spin coating of the CH3CH2NH3I and PbI2 mixed solution on a TiO2 film yields ca. 1.8-nm-diameter (CH3CH2NH3)PbI3 dots on the TiO2 surface. The (CH3CH2NH3)PbI3-sensitized solar cell with iodide-based redox electrolyte demonstrates the conversion efficiency of 2.4% under AM 1.5 G one sun (100 mW/cm2) illumination.
Tuning the dimensionality of ZnO nanowires through thermal treatment: An investigation of growth mechanism
Authors: Shih Po-Hsun , Hung Hsuan-Jung , Ma Yuan-Ron , Wu Sheng-Yun
Published: June 2012

In this study, we synthesized various dimensionalities of ZnO nanowires using the Ti grid-assisted chemical vapor deposition process. Energy dispersive X-ray spectroscopic mapping technique accompanied with a lattice diffusion model was used to characterize the growth mechanism. A diffusion ratio γ, defined by short-circuit and lattice diffusion activation energies, was obtained to describe the growth mechanism of ZnO nanowires. The tunable dimensionalities of ZnO nanowires allow us to modify the morphology of ZnO nanocrystals by developing well-controlled potential applications.
A pink mouse reports the switch from red to green fluorescence upon Cre-mediated recombination
Authors: Hartwich Heiner , Satheesh Somisetty V , Nothwang Hans Gerd
Published: June 2012

Background

Targeted genetic modification in the mouse becomes increasingly important in biomedical and basic science. This goal is most often achieved by use of the Cre/loxP system and numerous Cre-driver mouse lines are currently generated. Their initial characterization requires reporter mouse lines to study the in vivo spatiotemporal activity of Cre.

Findings

Here, we report a dual fluorescence reporter mouse line, which switches expression from the red fluorescent protein mCherry to eGFP after Cre-mediated recombination. Both fluorescent proteins are expressed from the ubiquitously active and strong CAGGS promoter. Among the founders, we noticed a pink mouse line, expressing high levels of the red fluorescent protein mCherry throughout the entire body. Presence of mCherry in the living animal as well as in almost all organs was clearly visible without optical equipment. Upon Cre-activity, mCherry expression was switched to eGFP, demonstrating functionality of this reporter mouse line.

Conclusions

The pink mouse presented here is an attractive novel reporter line for fluorescence-based monitoring of Cre-activity. The high expression of mCherry, which is visible to the naked eye, facilitates breeding and crossing, as no genotyping is required to identify mice carrying the reporter allele. The presence of two fluorescent proteins allows in vivo monitoring of recombined and non-recombined cells. Finally, the pink mouse is an eye-catching animal model to demonstrate the power of transgenic techniques in teaching courses.
Haemophilus influenzae and the lung (Haemophilus and the lung)
Authors: King Paul
Published: June 2012

Haemophilus influenzae is present as a commensal organism in the nasopharynx of most healthy adults from where it can spread to cause both systemic and respiratory tract infection. This bacterium is divided into typeable forms (such as type b) or nontypeable forms based on the presence or absence of a tough polysaccharide capsule. Respiratory disease is predominantly caused by the nontypeable forms (NTHi). Haemophilus influenzae has evolved a number of strategies to evade the host defense including the ability to invade into local tissue. Pathogenic properties of this bacterium as well as defects in host defense may result in the spread of this bacterium from the upper airway to the bronchi of the lung. This can result in airway inflammation and colonization particularly in chronic obstructive pulmonary disease. Treatment of respiratory tract infection with Haemophilus influenzae is often only partially successful with ongoing infection and inflammation. Improvement in patient outcome will be dependent on a better understanding of the pathogenesis and host immune response to this bacterium.
Common polymorphisms in GSTM1, GSTT1, GSTP1, GSTA1 and susceptibility to colorectal cancer in the Central European population
Authors: Hezova Renata , Bienertova-Vasku Julie , Sachlova Milana , Brezkova Veronika , Vasku Anna , Svoboda Marek , Radová Lenka , Kiss Igor , Vyzula Rostislav , Slaby Ondrej
Published: June 2012

Background

Central Europe presents with the highest incidence of sporadic colorectal cancer (CRC) worldwide. As sporadic CRC represents a typical multifactorial disease, it is characterized by intense interaction of the genetic background with the environment. Glutathione S-transferases could act as attractive susceptibility genes for CRC, as they are directly involved in conjugation between glutathione and chemotherapeutics, environmental pollutants and a wide spectrum of xenobiotics.

Methods

In this study, we investigated associations of polymorphisms in glutathione S-transferases (GSTs) genes, that is GSTA1, GSTT1, GSTM1 and GSTP1, with CRC in a total of 197 cases and 218 controls originating from the Czech Central European population. Polymorphisms were assessed by polymerase chain reaction/restriction fragment length polymorphism-based methods, allele-specific multiplex and allelic discrimination by real-time polymerase chain reaction.

Results

None of investigated polymorphisms showed any associations with CRC, with the exception of GSTP1; where the heterozygote genotype Ile105Val was associated with decreased risk of CRC (P = 0.043).

Conclusions

The frequencies observed in our study are in accordance with those from other European Caucasian populations. Based on our studies, examined variability in GST genes is not a major determinant of CRC susceptibility in the Central European population.
Quantiferon-TB Gold in tube assay for the screening of tuberculosis before and during treatment with tumor necrosis factor alpha antagonists
Authors: Hatemi Gulen , Melikoglu Melike , Ozbakir Fatma , Tascilar Koray , Yazici Hasan
Published: June 2012

Introduction

The usefulness of interferon-gamma (IFN-γ) release assays for tuberculosis screening before tumor necrosis factor-alpha (TNF-α) antagonists and for monitoring during treatment is a contraversial issue. The aims of this study were to determine whether TNF-α antagonists affect the results of the Quantiferon-TB Gold in-tube assay (QTF); to assess how QTF performs in comparison with the tuberculin skin test (TST) in rheumatoid arthritis (RA) patients who are about to start treatment with TNF-α antagonists, RA patients who are not candidates for treatment with TNF-α antagonists, rheumatology patients with confirmed current or past tuberculosis infection, and healthy controls, and to determine the specificity of the QTF test to differentiate leprosy patients, another group of patients infected with mycobacteria.

Methods

The 38 RA patients who were prescribed TNF-α antagonists, 40 RA patients who were not considered for TNF-α antagonist use, 30 rheumatology patients with a history or new diagnosis of tuberculosis, 23 leprosy patients, and 41 healthy controls were studied. QTF and TST were done on the same day, and both were repeated after a mean of 3.6 ± 0.2 months in patients who used TNF-α antagonists.

Results

Treatment with TNF-α antagonists did not cause a significant change in the QTF or TST positivity rate (34% versus 42%; P = 0.64; and 24% versus 37%; P = 0.22). Patients with leprosy had a trend for a higher mean IFN-γ level (7.3 ± 8.0) and QTF positivity (61%) than did the other groups; however, the difference was not significant (P = 0.09 and P = 0.43).

Conclusions

Treatment with TNF-α antagonists does not seem to affect the QTF test to an appreciable degree. The higher IFN-γ levels in leprosy patients deserves further attention.
Inhibitory effect of ginsenoside Rg1 on extracellular matrix production via extracellular signal-regulated protein kinase/activator protein 1 pathway in nasal polyp-derived fibroblasts
Authors: Cho Jung-Sun , Moon You-Mi , Um Ji-Young , Moon Jun-Hyeok , Park Il-Ho , Lee Heung-Man
Published: June 2012

Nasal polyps are associated with chronic inflammation of the sinonasal mucosa and are involved in myofibroblast differentiation and extracellular matrix (ECM) accumulation. Ginsenoside Rg1, a compound derived from Panax ginseng, shows antifibrotic and anticancer effects. However, the molecular effects of Rg1 on myofibroblast differentiation and ECM production remain unknown. The aims of this study were to investigate the effect of Rg1 on transforming growth factor (TGF)- β1-induced myofibroblast differentiation and ECM production and to determine the molecular mechanism of Rg1 in nasal polyp-derived fibroblasts (NPDFs). NPDFs were isolated from nasal polyps of seven patients who had chronic rhinosinusitis with nasal polyp. NPDFs were exposed to TGF- β1 with or without Rg1. Expression levels of α-smooth muscle actin (SMA), fibronectin and collagen type I α1 were determined by reverse transcription polymerase chain reaction, Western blot and immunofluorescent staining. TGF- β1 signaling molecules, including Smad2/3, extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 were analyzed by Western blotting. Transcription factors involved with TGF- β1 signaling, nuclear factor (NF)- κB and activator protein 1 (AP-1) were also assessed by Western blot. The cytotoxic effect of Rg1 was measured by an established viability assay. The mRNA and protein expression levels of α-SMA, fibronectin and collagen type I α1 were increased in TGF- β1-induced NPDFs. Rg1 inhibited these effects. The inhibitory molecular mechanism of Rg1 was involved in the ERK pathway. Rg1 inhibited the transcription factor activation of AP-1. Rg1 itself was not cytotoxic. The ginsenoside Rg1 has inhibitory effects on myofibroblast differentiation and ECM production. The inhibitory mechanism of Rg1 is involved with the ERK and AP-1 signaling pathways. Rg1 may be useful as an inhibitor of ECM deposition, and has potential to be used as a novel treatment option for nasal polyps.
Pharmacological inhibition of ATM by KU55933 stimulates ATM transcription
Authors: Khalil Hilal S , Tummala Hemanth , Hupp Tedd R , Zhelev Nikolai
Published: June 2012

Ataxia-telangiectasia mutated (ATM) kinase is a component of a signalling mechanism that determines the process of decision-making in response to DNA damage and involves the participation of multiple proteins. ATM is activated by DNA double-strand breaks (DSBs) through the Mre11–Rad50–Nbs1 (MRN) DNA repair complex, and orchestrates signalling cascades that initiate the DNA damage response. Cells lacking ATM are hypersensitive to insults, particularly genotoxic stress, induced through radiation or radiomimetic drugs. Here, we investigate the degree of ATM activation during time-dependent treatment with genotoxic agents and the effects of ATM on phospho-induction and localization of its downstream substrates. Additionally, we have demonstrated a new cell-cycle-independent mechanism of ATM gene regulation following ATM kinase inhibition with KU5593. Inhibition of ATM activity causes induction of ATM protein followed by oscillation and this mechanism is governed at the transcriptional level. Furthermore, this autoregulatory induction of ATM is also accompanied by a transient upregulation of p53, pATR and E2F1 levels. Since ATM inhibition is believed to sensitize cancer cells to genotoxic agents, this novel insight into the mechanism of ATM regulation might be useful for designing more precise strategies for modulation of ATM activity in cancer therapy.
Mucosal immunization with caseinolytic protease X elicited cross-protective immunity against pneumococcal infection in mice
Authors: Zhong Wen , Xu Wenchun , Wang Hong , Huang Yuanshuai , Cao Ju , Gong Yi , Xu Xiuyu , Min Xun , Zhang Yanqing , Dong Jie , Yin Yibing , Zhang Xuemei
Published: June 2012

Streptococcus pneumoniae resides on the mucosal surface of the upper respiratory tract and is ready to spread and trigger clinical diseases. Hence the vaccine that can eliminate the nasopharyngeal colonization was thought to be an ideal protective strategy against pneumococcal invasive diseases. Caseinolytic protease X (ClpX), a pneumococcal caseinolytic protease ATPase subunit, was shown to be a non-transmembrane protein by bioinformatics analysis. Consistent with the in silico prediction, the secretory expression of ClpX, instead of surface exposure, was further confirmed by flow cytometry and Western blot. Furthermore, ClpX was highly conserved in nine different serotypes of S. pneumoniae at both gene and protein concentrations. In addition, the anti-ClpX IgG antibody levels in human serum samples were much higher in healthy children, compared with pediatric patients, and displayed an age-related increase. Finally, ClpX protein antigen was introduced to BALB/c mice through a mucosal route, and protection against nasopharyngeal colonization and lethal infection caused by different S. pneumoniae serotypes was successfully elicited. Our findings suggest that ClpX is a potential candidate antigen that could be incorporated in pneumococcal protein vaccines.
Antioxidant potential of different melatonin-loaded nanomedicines in an experimental model of sepsis
Authors: Li Volti Giovanni , Musumeci Teresa , Pignatello Rosario , Murabito Paolo , Barbagallo Ignazio , Carbone Claudia , Gullo Antonino , Puglisi Giovanni
Published: June 2012

Oxidative stress has been shown to play a major role in the complex pathophysiological processes leading to organ failure during sepsis. The aim of the present research was to evaluate the effect of different melatonin nanoparticle (NP) carriers in an experimental animal model of sepsis. Poly-d,l-lactide-co-glycolide (PLGA [NP-A]) and polyethylene glycol-co-(poly-d,l-lactide-co-glycolide) (PLGA-PEG [NP-B]) were used to obtain melatonin-loaded nanocarriers (10 mg/kg). Oxidative stress was measured in tissue homogenates by measuring heme oxygenase-1 (HO-1) expression, total thiol groups and lipid hydroperoxides (LOOH). In vitro NPs showed a long lag time followed by a controlled release of melatonin. All the different melatonin formulations restored total thiol group levels to those of controls in all the examined organs, with no significant changes among them. Both melatonin NP formulations significantly decreased LOOH levels when compared with sepsis vehicle animals. The stealth formulation NP-B was able to produce a more significant reduction in LOOH levels in the heart, lung and liver when compared with NP-A. No significant changes were observed between the two NP formulations in the kidney. Interestingly, HO-1 expression was differently affected following treatment with various melatonin formulations. The NP-B formulation was more effective in inducing HO-1 protein compared with free melatonin and NP-A, with the exception of the kidney. Taken together, our results show that melatonin possesses a significant antioxidant activity during sepsis and that it is possible to improve this ability by delivering the compound with specific drug delivery systems.
Stemness gene expression profile analysis in human umbilical cord mesenchymal stem cells
Authors: Meng Ming-Yao , Pang Wei , Jiang Li-Hong , Liu Yun-Hong , Wei Chuan-Yu , Xie Yan-Hua , Yu Hai-Dong , Hou Zong-Liu
Published: June 2012

Umbilical cord mesenchymal stem cells (UC-MSCs) have several advantages for clinical therapy: the material is easily obtainable, the donation procedure is painless and there is low risk of viral contamination. UC-MSCs play important roles in tissue regeneration, tissue damage repair, autoimmune disease and graft-versus-host disease. In this study, we investigated the normal mRNA expression profile of UC-MSCs, and analyzed the candidate proteins responsible for the signaling pathway that may affect the differentiation characteristics of UC-MSCs. UC-MSCs were isolated by mincing UC samples into fragments and placing them in growth medium in a six-well plate. The immunophenotype characteristics and multilineage differentiation potential of the UC-MSCs were measured by flow cytometry and immunohistochemical assays. In addition, the pathway-focused gene expression profile of UC-MSCs was compared with those of normal or tumorous cells by realtime quantitative polymerase chain reaction. We successfully isolated and cultured UC-MSCs and analyzed the appropriate surface markers and their capacity for osteogenic, adipogenic and neural differentiation. In total, 168 genes focusing on signal pathways were examined. We found that the expression levels of some genes were much higher or lower than those of control cells, either normal or tumorous. UC-MSCs exhibit a unique mRNA expression profile of pathway-focused genes, especially some stemness genes, which warrants further investigation.
Novel vascular endothelial growth factor gene delivery system-manipulated mesenchymal stem cells repair infarcted myocardium
Authors: Zhu Kai , Lai Hao , Guo Changfa , Xu Demin , Wang Chunsheng
Published: June 2012

Transplantation of vascular endothelial growth factor (VEGF) gene-manipulated mesenchymal stem cells (MSCs) has been proposed as a promising therapy strategy for cardiac repair after myocardium infarction. However, the gene delivery system, including targeted VEGF gene and delivery vehicle, still needs to be optimized. In this study, a novel, hyperbranched poly(amidoamine) (hPAMAM), polymer-based, hypoxia-regulated VEGF165 plasmid (pHRE-VEGF165) delivery system was constructed for effective, biocompatible and controllable gene expression. The hPAMAM demonstrated high transfection efficiency (38.98 ± 1.95%) with minor cytotoxicity (cell viability = 92.38 ± 1.09%) in primary MSCs under optimal conditions. Under hypoxia, hPAMAM-pHRE-hVEGF165-transfected MSCs could over-express hVEGF165 stably for 14 days, with a peak expression at day 2, which promoted endothelial cell proliferation in vitro. The transplantation of hPAMAM-pHRE-hVEGF165 gene delivery system-manipulated MSCs could enhance ischemic myocardium VEGF concentration obviously, which improved the graft MSC survival, increased neovascularization, and ultimately preserved cardiac function to a significantly greater degree than untreated MSC transplantation. This work demonstrated that hPAMAM-based pHRE-hVEGF165 gene delivery combined with MSC transplantation is an economical, feasible and biocompatible strategy for cardiac repair.
Mid- to long-term results of revision total knee replacement using press-fit intramedullary stems with cemented femoral and tibial components
Authors: Manopoulos P. , Havet E. , Pearce O. , Lardanchet J. F. , Mertl P.
Published: June 2012

This was a retrospective analysis of the medium- to long-term results of 46 TC3 Sigma revision total knee replacements using long uncemented stems in press-fit mode.

Clinical and radiological analysis took place pre-operatively, at two years post-operatively, and at a mean follow-up of 8.5 years (4 to 12). The mean pre-operative International Knee Society (IKS) clinical score was 42 points (0 to 74), improving to 83.7 (52 to 100) by the final follow-up. The mean IKS score for function improved from 34.3 points (0 to 80) to 64.2 (15 to 100) at the final follow-up. At the final follow-up 30 knees (65.2%) had an excellent result, seven (15.2%) a good result, one (2.2%) a medium and eight (17.4%) a poor result. There were two failures, one with anteroposterior instability and one with aseptic loosening.

The TC3 revision knee system, when used with press-fit for long intramedullary stems and cemented femoral and tibial components, in both septic and aseptic revisions, results in a satisfactory clinical and radiological outcome, and has a good medium- to long-term survival rate.
In vivo bioluminescence imaging of transplanted bone marrow mesenchymal stromal cells using a magnetic delivery system in a rat fracture model
Authors: Kodama A. , Kamei N. , Kamei G. , Kongcharoensombat W. , Ohkawa S. , Nakabayashi A. , Ochi M.
Published: June 2012

For the treatment of ununited fractures, we developed a system of delivering magnetic labelled mesenchymal stromal cells (MSCs) using an extracorporeal magnetic device. In this study, we transplanted ferucarbotran-labelled and luciferase-positive bone marrow-derived MSCs into a non-healing femoral fracture rat model in the presence of a magnetic field. The biological fate of the transplanted MSCs was observed using luciferase-based bioluminescence imaging and we found that the number of MSC derived photons increased from day one to day three and thereafter decreased over time. The magnetic cell delivery system induced the accumulation of photons at the fracture site, while also retaining higher photon intensity from day three to week four. Furthermore, radiological and histological findings suggested improved callus formation and endochondral ossification. We therefore believe that this delivery system may be a promising option for bone regeneration.
A case-control study of spontaneous patellar fractures following primary total knee replacement
Authors: Seo J. G. , Moon Y. W. , Park S. H. , Lee J. H. , Kang H. M. , Kim S. M.
Published: June 2012

Peri-prosthetic patellar fracture following resurfacing as part of total knee replacement (TKR) is an infrequent yet challenging complication. This case-control study was performed to identify clinical, radiological and surgical factors that increase the risk of developing a spontaneous patellar fracture after TKR. Patellar fractures were identified in 74 patients (88 knees) from a series of 7866 consecutive TKRs conducted between 1998 and 2009. After excluding those with a previous history of extensor mechanism realignment or a clear traumatic event, a metal-backed patella, any uncemented component or subsequent infection, the remaining 64 fractures were compared with a matched group of TKRs with an excellent outcome defined by the Knee Society score. The mean age of patients with a fracture was 70 years (51 to 81) at the time of TKR. Patellar fractures were detected at a mean of 13.4 months (2 to 84) after surgery. The incidence of patellar fracture was found to be strongly associated with the number of previous knee operations, greater pre-operative mechanical malalignment, smaller post-operative patellar tendon length, thinner post-resection patellar thickness, and a lower post-operative Insall-Salvati ratio.

An understanding of the risk factors associated with spontaneous patellar fracture following TKR provides a valuable insight into prevention of this challenging complication.