bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of overweight and obesity among Chinese Yi nationality: a cross-sectional study
Authors: Gao Yun , Ran Xing-Wu , Xie Xiao-Hua , Lu Hua-Lin , Chen Tao , Ren Yan , Long Yang , Tian Hao-Ming
Published: December 2011

Background

Overweight and obesity are considered a serious health problem. There are little data on the prevalence of overweight and obesity among the Yi ethnic group in China. This study aimed to investigate the epidemiologic features of overweight/obesity among Chinese Yi nationality.

Methods

A cross-sectional study, including 1255 subjects aged 20-75 years, was carried out in Liangshan Yi Autonomous Prefecture of Sichuan province from 2007 to 2008. Overweight/overall obesity was defined by World Health Organization (WHO) or the Working Group on Obesity in China.

Results

Overall, the prevalence of overweight and obesity was 19.0% and 2.9%, respectively, based on the WHO definition, while it was 21.0% and 7.4%, respectively, according to the Working Group on Obesity in China, which is similar to data reported in the 2002 Chinese National Nutrition and Health Survey. Urban residents had a significantly higher prevalence of obesity (WHO criteria: 4.3% vs 1.7% p = 0.008; China criteria: 11.4% vs 3.7%, p < 0.001) and overweight (WHO criteria: 28.9% vs 8.9% p < 0.001; China criteria: 31.2% vs 10.4%, p < 0.001) than that in rural residents. Older age, a family history of obesity, higher income, drinking and urban residence were significantly associated with an increased risk of overweight/obesity.

Conclusions

The prevalence of overweight/obesity in the Yi nationality is similar to that in Chinese adults 5 years ago. However, urban residents have a much higher prevalence of overweight/obesity than their rural counterparts. Lifestyle and diet patterns associated with socioeconomic status may explain the difference between urban and rural residents. The prevention of overweight/obesity among urban inhabitants deserves more attention in national health education programs.
Ecological Niche Modelling of the Bacillus anthracis A1.a sub-lineage in Kazakhstan
Authors: Mullins Jocelyn , Lukhnova Larissa , Aikimbayev Alim , Pazilov Yerlan , Van Ert Matthew , Blackburn Jason K
Published: December 2011

Background

Bacillus anthracis, the causative agent of anthrax, is a globally distributed zoonotic pathogen that continues to be a veterinary and human health problem in Central Asia. We used a database of anthrax outbreak locations in Kazakhstan and a subset of genotyped isolates to model the geographic distribution and ecological associations of B. anthracis in Kazakhstan. The aims of the study were to test the influence of soil variables on a previous ecological niche based prediction of B. anthracis in Kazakhstan and to determine if a single sub-lineage of B. anthracis occupies a unique ecological niche.

Results

The addition of soil variables to the previously developed ecological niche model did not appreciably alter the limits of the predicted geographic or ecological distribution of B. anthracis in Kazakhstan. The A1.a experiment predicted the sub-lineage to be present over a larger geographic area than did the outbreak based experiment containing multiple lineages. Within the geographic area predicted to be suitable for B. anthracis by all ten best subset models, the A1.a sub-lineage was associated with a wider range of ecological tolerances than the outbreak-soil experiment. Analysis of rule types showed that logit rules predominate in the outbreak-soil experiment and range rules in the A1.a sub-lineage experiment. Random sub-setting of locality points suggests that models of B. anthracis distribution may be sensitive to sample size.

Conclusions

Our analysis supports careful consideration of the taxonomic resolution of data used to create ecological niche models. Further investigations into the environmental affinities of individual lineages and sub-lineages of B. anthracis will be useful in understanding the ecology of the disease at large and small scales. With model based predictions serving as approximations of disease risk, these efforts will improve the efficacy of public health interventions for anthrax prevention and control.
Heterologous overexpression of Glomerella cingulata FAD-dependent glucose dehydrogenase in Escherichia coli and Pichia pastoris
Authors: Sygmund Christoph , Staudigl Petra , Klausberger Miriam , Pinotsis Nikos , Djinović-Carugo Kristina , Gorton Lo , Haltrich Dietmar , Ludwig Roland
Published: December 2011

Background

FAD dependent glucose dehydrogenase (GDH) currently raises enormous interest in the field of glucose biosensors. Due to its superior properties such as high turnover rate, substrate specificity and oxygen independence, GDH makes its way into glucose biosensing. The recently discovered GDH from the ascomycete Glomerella cingulata is a novel candidate for such an electrochemical application, but also of interest to study the plant-pathogen interaction of a family of wide-spread, crop destroying fungi. Heterologous expression is a necessity to facilitate the production of GDH for biotechnological applications and to study its physiological role in the outbreak of anthracnose caused by Glomerella (anamorph Colletotrichum) spp.

Results

Heterologous expression of active G. cingulata GDH has been achieved in both Escherichia coli and Pichia pastoris, however, the expressed volumetric activity was about 4800-fold higher in P. pastoris. Expression in E. coli resulted mainly in the formation of inclusion bodies and only after co-expression with molecular chaperones enzymatic activity was detected. The fed-batch cultivation of a P. pastoris transformant resulted in an expression of 48,000 U L-1 of GDH activity (57 mg L-1). Recombinant GDH was purified by a two-step purification procedure with a yield of 71%. Comparative characterization of molecular and catalytic properties shows identical features for the GDH expressed in P. pastoris and the wild-type enzyme from its natural fungal source.

Conclusions

The heterologous expression of active GDH was greatly favoured in the eukaryotic host. The efficient expression in P. pastoris facilitates the production of genetically engineered GDH variants for electrochemical-, physiological- and structural studies.
A novel cold-active β-D-galactosidase from the Paracoccus sp. 32d - gene cloning, purification and characterization
Authors: Wierzbicka-Woś Anna , Cieśliński Hubert , Wanarska Marta , Kozłowska-Tylingo Katarzyna , Hildebrandt Piotr , Kur Józef
Published: December 2011

Background

β-D-Galactosidases (EC 3.2.1.23) catalyze the hydrolysis of terminal non-reducing β-D-galactose residues in β-D-galactosides. Cold-active β-D-galactosidases have recently become a focus of attention of researchers and dairy product manufactures owing to theirs ability to: (i) eliminate of lactose from refrigerated milk for people afflicted with lactose intolerance, (ii) convert lactose to glucose and galactose which increase the sweetness of milk and decreases its hydroscopicity, and (iii) eliminate lactose from dairy industry pollutants associated with environmental problems. Moreover, in contrast to commercially available mesophilic β-D-galactosidase from Kluyveromyces lactis the cold-active counterparts could make it possible both to reduce the risk of mesophiles contamination and save energy during the industrial process connected with lactose hydrolysis.

Results

A genomic DNA library was constructed from soil bacterium Paracoccus sp. 32d. Through screening of the genomic DNA library on LB agar plates supplemented with X-Gal, a novel gene encoding a cold-active β-D-galactosidase was isolated. The in silico analysis of the enzyme amino acid sequence revealed that the β-D-galactosidase Paracoccus sp. 32d is a novel member of Glycoside Hydrolase Family 2. However, owing to the lack of a BGal_small_N domain, the domain characteristic for the LacZ enzymes of the GH2 family, it was decided to call the enzyme under study 'BgaL'. The bgaL gene was cloned and expressed in Escherichia coli using the pBAD Expression System. The purified recombinant BgaL consists of two identical subunits with a combined molecular weight of about 160 kDa. The BgaL was optimally active at 40°C and pH 7.5. Moreover, BgaL was able to hydrolyze both lactose and o-nitrophenyl-β-D-galactopyranoside at 10°C with K
m values of 2.94 and 1.17 mM and k
cat values 43.23 and 71.81 s-1, respectively. One U of the recombinant BgaL would thus be capable hydrolyzing about 97% of the lactose in 1 ml of milk in 24 h at 10°C.

Conclusions

A novel bgaL gene was isolated from Paracoccus sp. 32d encoded a novel cold-active β-D-galactosidase. An E. coli expression system has enabled efficient production of soluble form of BgaL Paracoccus sp. 32d. The amino acid sequence analysis of the BgaL enzyme revealed notable differences in comparison to the result of the amino acid sequences analysis of well-characterized cold-active β-D-galactosidases belonging to Glycoside Hydrolase Family 2. Finally, the enzymatic properties of Paracoccus sp. 32d β-D-galactosidase shows its potential for being applied to development of a new industrial biocatalyst for efficient lactose hydrolysis in milk.
Cross-linking cellulose nanofibrils for potential elastic cryo-structured gels
Authors: Syverud Kristin , Kirsebom Harald , Hajizadeh Solmaz , Chinga-Carrasco Gary
Published: December 2011

Cellulose nanofibrils were produced from P. radiata kraft pulp fibers. The nanofibrillation was facilitated by applying 2,2,6,6-tetramethylpiperidinyl-1-oxyl-mediated oxidation as pretreatment. The oxidized nanofibrils were cross-linked with polyethyleneimine and poly N-isopropylacrylamide-co-allylamine-co-methylenebisacrylamide particles and were frozen to form cryo-structured gels. Samples of the gels were critical-point dried, and the corresponding structures were assessed with scanning electron microscopy. It appears that the aldehyde groups in the oxidized nanofibrils are suitable reaction sites for cross-linking. The cryo-structured materials were spongy, elastic, and thus capable of regaining their shape after a given pressure was released, indicating a successful cross-linking. These novel types of gels are considered potential candidates in biomedical and biotechnological applications.
Improving network energy efficiency through cooperative idling in the multi-cell systems
Authors: Xu Jie , Qiu Ling , Yu Chengwen
Published: December 2011

Network energy efficiency (NEE) is considered as the metric to address the energy efficiency problem in the cooperative multi-cell systems in this article. At first, three typical schemes with different levels of cooperation, i.e., interference aware game theory, inter-cell interference cancellation, and multi-cell joint processing, are discussed. For both unconstrained and constrained case, efficient power control strategies are developed to maximize the NEE. During the optimization, both the optimization objects and strategies are distinct because of different levels of data and channel state information at the transmitter sharing. In order to further improve NEE, a novel cooperative idling (CI) scheme is proposed through cooperatively switching some BSs into micro-sleep and guaranteeing the data transmission with the other active BSs' cooperative transmission. Simulation results indicate that cooperation can improve both NEE and network capacity and demonstrate that CI can further improve the NEE significantly.
Biomarkers of acute lung injury: worth their salt?
Authors: Proudfoot Alastair G , Hind Matthew , Griffiths Mark JD
Published: December 2011

The validation of biomarkers has become a key goal of translational biomedical research. The purpose of this article is to discuss the role of biomarkers in the management of acute lung injury (ALI) and related research. Biomarkers should be sensitive and specific indicators of clinically important processes and should change in a relevant timeframe to affect recruitment to trials or clinical management. We do not believe that they necessarily need to reflect pathogenic processes. We critically examined current strategies used to identify biomarkers and which, owing to expedience, have been dominated by reanalysis of blood derived markers from large multicenter Phase 3 studies. Combining new and existing validated biomarkers with physiological and other data may add predictive power and facilitate the development of important aids to research and therapy.
Polymerase activity of hybrid ribonucleoprotein complexes generated from reassortment between 2009 pandemic H1N1 and seasonal H3N2 influenza A viruses
Authors: Lam Wai Y , Ngai Karry LK , Chan Paul KS
Published: December 2011

Background

A novel influenza virus (2009 pdmH1N1) was identified in early 2009 and progressed to a pandemic in mid-2009. This study compared the polymerase activity of recombinant viral ribonucleoprotein (vRNP) complexes derived from 2009 pdmH1N1 and the co-circulating seasonal H3N2, and their possible reassortants.

Results

The 2009 pdmH1N1 vRNP showed a lower level of polymerase activity at 33°C compared to 37°C, a property remenisence of avian viruses. The 2009 pdmH1N1 vRNP was found to be more cold-sensitive than the WSN or H3N2 vRNP. Substituion of 2009 pdmH1N1 vRNP with H3N2-derived-subunits, and vice versa, still retained a substantial level of polymerase activity, which is probably compartable with survival. When the 2009 pdmH1N1 vRNP was substituted with H3N2 PA, a significant increase in activity was observed; whereas when H3N2 vRNP was substituted with 2009 pdmH1N1 PA, a significant decrease in activity occurred. Although, the polymerase basic protein 2 (PB2) of 2009 pdmH1N1 was originated from an avian virus, substitution of this subunit with H3N2 PB2 did not change its polymerase activity in human cells.

Conclusions

In conclusion, our data suggest that hybrid vRNPs resulted from reassortment between 2009 pdmH1N1 and H3N2 viruses could still retain a substantial level of polymerase activity. Substituion of the subunit PA confers the most prominent effect on polymerase activity. Further studies to explore the determinants for polymerase activity of influenza viruses in associate with other factors that limit host specificity are warrant.
Human herpesvirus 6A induces apoptosis of primary human fetal astrocytes via both caspase-dependent and -independent pathways
Authors: Gu Bin , Zhang Guo-Feng , Li Ling-Yun , Zhou Feng , Feng Dong-Ju , Ding Chuan-Lin , Chi Jing , Zhang Chun , Guo Dan-Dan , Wang Jing-Feng , Zhou Hong , Yao Kun , Hu Wei-Xing
Published: December 2011

Background

Human herpesvirus 6 (HHV-6) is a T-lymphtropic and neurotropic virus that can infect various types of cells. Sequential studies reported that apoptosis of glia and neurons induced by HHV-6 might act a potential trigger for some central nervous system (CNS) diseases. HHV-6 is involved in the pathogenesis of encephalitis, multiple sclerosis (MS) and fatigue syndrome. However, the mechanisms responsible for the apoptosis of infected CNS cells induced by HHV-6 are poorly understood. In this study, we investigated the cell death processes of primary human fetal astrocytes (PHFAs) during productive HHV-6A infection and the underlying mechanisms.

Results

HHV-6A can cause productive infection in primary human fetal astrocytes. Annexin V-PI staining and electron microscopic analysis indicated that HHV-6A was an inducer of apoptosis. The cell death was associated with activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP), which is known to be an important substrate for activated caspase-3. Caspase-8 and -9 were also significantly activated in HHV-6A-infected cells. Moreover, HHV-6A infection led to Bax up-regulation and Bcl-2 down-regulation. HHV-6A infection increased the release of Smac/Diablo, AIF and cytochrome c from mitochondria to cytosol, which induced apoptosis via the caspase-dependent and -independent pathways. In addition, we also found that anti-apoptotic factors such as IAPs and NF-κB decreased in HHV-6A infected PHFAs.

Conclusion

This is the first demonstration of caspase-dependent and -independent apoptosis in HHV-6A-infected glial cells. These findings would be helpful in understanding the mechanisms of CNS diseases caused by HHV-6.
Observations on rift valley fever virus and vaccines in Egypt
Authors: Ahmed Kamal Samia
Published: December 2011

Rift Valley Fever virus (RVFV, genus: Phlebovirus, family: Bunyaviridae), is an arbovirus which causes significant morbidity and mortality in animals and humans. RVFV was introduced for the first time in Egypt in 1977. In endemic areas, the insect vector control and vaccination is considering appropriate measures if applied properly and the used vaccine is completely safe and the vaccination programs cover all the susceptible animals. Egypt is importing livestock and camels from the African Horn & the Sudan for human consumption. The imported livestock and camels were usually not vaccinated against RVFV. But in rare occasions, the imported livestock were vaccinated but with unknown date of vaccination and the unvaccinated control contacts were unavailable for laboratory investigations. Also, large number of the imported livestock and camels are often escaped slaughtering for breeding which led to the spread of new strains of FMD and the introduction of RVFV from the enzootic African countries. This article provide general picture about the present situation of RVFV in Egypt to help in controlling this important disease.
Correlation between LTR point mutations and proviral load levels among Human T cell Lymphotropic Virus type 1 (HTLV-1) asymptomatic carriers
Authors: Neto Walter K , Da-Costa Antonio C , de Oliveira AnaCarolina S , Martinez Vanessa P , Nukui Youko , Sabino Ester C , Sanabani Sabri S
Published: December 2011

Background

In vitro studies have demonstrated that deletions and point mutations introduced into each 21 bp imperfect repeat of Tax-responsive element (TRE) of the genuine human T-cell leukemia virus type I (HTLV-1) viral promoter abolishes Tax induction. Given these data, we hypothesized that similar mutations may affect the proliferation of HTLV-1i

nfected cells and alter the proviral load (PvL). To test this hypothesis, we conducted a cross-sectional genetic analysis to compare the near-complete LTR nucleotide sequences that cover the TRE1 region in a sample of HTLV-1 asymptomatic carriers with different PvL burden.

Methods

A total of 94 asymptomatic HTLV-1 carriers with both sequence from the 5' long terminal repeat (LTR) and a PvL for Tax DNA measured using a sensitive SYBR Green real-time PCR were studied. The 94 subjects were divided into three groups based on PvL measurement: 31 low, 29 intermediate, and 34 high. In addition, each group was compared based on sex, age, and viral genotypes. In another analysis, the median PvLs between individuals infected with mutant and wild-type viruses were compared.

Results

Using a categorical analysis, a G232A substitution, located in domain A of the TRE-1 motif, was detected in 38.7% (12/31), 27.5% (8/29), and 61.8% (21/34) of subjects with low, intermediate, or high PvLs, respectively. A significant difference in the detection of this mutation was found between subjects with a high or low PvL and between those with a high or intermediate PvL (both p < 0.05), but not between subjects with a low or intermediate PvL (p > 0.05). This result was confirmed by a non-parametric analysis that showed strong evidence for higher PvLs among HTLV-1 positive individuals with the G232A mutation than those without this mutation (p < 0.03). No significant difference was found between the groups in relation to age, sex or viral subtypes (p > 0. 05).

Conclusions

The data described here show that changes in domain A of the HTLV-1 TRE-1 motif resulting in the G232A mutation may increase HTLV-1 replication in a majority of infected subjects.
Incense and ritual plant use in Southwest China: A case study among the Bai in Shaxi
Authors: Staub Peter O , Geck Matthias S , Weckerle Caroline S
Published: December 2011

Background

Ritual and religious uses of plant-derived smoke are widespread throughout the world. Our research focuses on Southwest China, where the use of incense is very common. This study aims to document and analyze contemporary ritual plant uses by the Bai people of Shaxi Township (Jianchuan County, Dali Prefecture, Yunnan Province), including their related ethnobotanical knowledge, practices, and beliefs.

Methods

The present study builds on previous ethnobotanical research in Shaxi, which started in 2005. Interviews focusing on ritual plant use and associated beliefs were carried out with a total of 44 Bai informants in September 2009 and May and June 2010. The results are supplemented with information on the local religion collected from June to December 2010. All documented species were vouchered, and are deposited at the herbaria of Kunming Institute of Botany (KUN) and the University of Zurich (Z/ZT).

Results

A total of 17 species have been documented for use in incense. They are always used in mixtures and are either burned in the form of powders in a censer or as joss sticks. The smell of the smoke is the main criterion for the selection of the incense plants. Incense is burned for communication with spiritual entities at graves, temples, and cooking stoves, as well as for personal well-being. Cupressus funebris Endl., Gaultheria fragrantissima Wall., and Ligustrum sempervirens (Franch.) Lingelsh. are the most important incense species. Others serve as substitutes or are used to stretch incense powders.

Conclusions

In Shaxi the use of incense mixtures at the household and community level is regularly practiced for communication with ancestors, ghosts, and deities and in some cases to strengthen self-awareness. Some of the documented species are widely used in central Asia and Europe, hinting at the well documented knowledge exchange that occurred in Shaxi, which was a major hub along the influential Southern Silk Road.
An in vivo root hair assay for determining rates of apoptotic-like programmed cell death in plants
Authors: Hogg Bridget V , Kacprzyk Joanna , Molony Elizabeth M , O'Reilly Conor , Gallagher Thomas F , Gallois Patrick , McCabe Paul F
Published: December 2011

In Arabidopsis thaliana we demonstrate that dying root hairs provide an easy and rapid in vivo model for the morphological identification of apoptotic-like programmed cell death (AL-PCD) in plants. The model described here is transferable between species, can be used to investigate rates of AL-PCD in response to various treatments and to identify modulation of AL-PCD rates in mutant/transgenic plant lines facilitating rapid screening of mutant populations in order to identify genes involved in AL-PCD regulation.
MiRNA expression patterns predict survival in glioblastoma
Authors: Niyazi Maximilian , Zehentmayr Franz , Niemöller Olivier M , Eigenbrod Sabina , Kretzschmar Hans , Schulze-Osthoff Klaus , Tonn Jörg-Christian , Atkinson Mike , Mörtl Simone , Belka Claus
Published: December 2011

Background

In order to define new prognostic subgroups in patients with glioblastoma a miRNA screen (> 1000 miRNAs) from paraffin tissues followed by a bio-mathematical analysis was performed.

Methods

35 glioblastoma patients treated between 7/2005 - 8/2008 at a single institution with surgery and postoperative radio(chemo)therapy were included in this retrospective analysis. For microarray analysis the febit biochip "Geniom®Biochip MPEA homo-sapiens" was used. Total RNA was isolated from FFPE tissue sections and 1100 different miRNAs were analyzed.

Results

It was possible to define a distinct miRNA expression pattern allowing for a separation of distinct prognostic subgroups. The defined miRNA pattern was significantly associated with early death versus long-term survival (split at 450 days) (p = 0.01). The pattern and the prognostic power were both independent of the MGMT status.

Conclusions

At present, this is the first dataset defining a prognostic role of miRNA expression patterns in patients with glioblastoma. Having defined such a pattern, a prospective validation of this observation is required.
Genomic alterations in rectal tumors and response to neoadjuvant chemoradiotherapy: an exploratory study
Authors: Molinari Chiara , Ballardini Michela , Teodorani Nazario , Giannini Massimo , Zoli Wainer , Emiliani Ermanno , Lucci Enrico , Passardi Alessandro , Rosetti Paola , Saragoni Luca , Guidoboni Massimo , Amadori Dino , Calistri Daniele
Published: December 2011

Background

Neoadjuvant chemoradiotherapy is the treatment of choice in advanced rectal cancer, even though there are many patients who will not benefit from it. There are still no effective methods for predicting which patients will respond or not. The present study aimed to define the genomic profile of rectal tumors and to identify alterations that are predictive of response in order to optimize therapeutic strategies.

Methods

Forty-eight candidates for neoadjuvant chemoradiotherapy were recruited and their pretherapy biopsies analyzed by array Comparative Genomic Hybridization (aCGH). Pathologic response was evaluated by tumor regression grade.

Results

Both Hidden Markov Model and Smoothing approaches identified similar alterations, with a prevalence of DNA gains. Non responsive patients had a different alteration profile from responsive ones, with a higher number of genome changes mainly located on 2q21, 3q29, 7p22-21, 7q21, 7q36, 8q23-24, 10p14-13, 13q12, 13q31-34, 16p13, 17p13-12 and 18q23 chromosomal regions.

Conclusions

This exploratory study suggests that an in depth characterization of chromosomal alterations by aCGH would provide useful predictive information on response to neoadjuvant chemoradiotherapy and could help to optimize therapy in rectal cancer patients.

The data discussed in this study are available on the NCBI Gene Expression Omnibus [GEO: GSE25885].
Histopathological and parasitological study of the gastrointestinal tract of dogs naturally infected with Leishmania infantum
Authors: Pinto Aldair JW , Figueiredo Maria M , Silva Fabiana L , Martins Trycia , Michalick Marilene SM , Tafuri Washington L , Tafuri Wagner L
Published: December 2011

Background

The aim of this study was to provide a systematic pathological and parasitological overview of the gastrointestinal tract (GIT), including the stomach, duodenum, jejunum, ileum, caecum and colon, of dogs naturally infected with Leishmania.

Methods

Twenty mongrel dogs naturally infected with Leishmania (Leishmania) infantum and obtained from the Control Zoonosis Center of the Municipality of Ribeirão das Neves, Belo Horizonte Metropolitan area, Minas Gerais (MG) state, Brazil, were analyzed. The dogs were divided into two groups: Group 1 comprised nine clinically normal dogs and group 2 comprised 11 clinically affected dogs. After necropsy, one sample was collected from each GIT segment, namely the stomach, duodenum, jejunum, ileum, caecum and colon. Furthermore, paraffin-embedded samples were used for histological and parasitological (immunohistochemistry) evaluation and a morphometrical study were carried out to determine the parasite load (immunolabeled amastigote forms of Leishmania). The Friedman and the Mann Whitney tests were used for statistical analysis. The Friedman test was used to analyze each segment of the GIT within each group of dogs and the Mann Whitney test was used to compare the GIT segments between clinically unaffected and affected dogs.

Results

The infected dogs had an increased number of macrophages, plasma cells and lymphocytes, but lesions were generally mild. Parasite distribution in the GIT was evident in all intestinal segments and layers of the intestinal wall (mucosal, muscular and submucosal) irrespective of the clinical status of the dogs. However, the parasite load was statistically higher in the caecum and colon than in other segments of the GIT.

Conclusion

The high parasite burden evident throughout the GIT mucosa with only mild pathological alterations led us to consider whether Leishmania gains an advantage from the intestinal immunoregulatory response (immunological tolerance).
Integrated prevalence mapping of schistosomiasis, soil-transmitted helminthiasis and malaria in lakeside and island communities in Lake Victoria, Uganda
Authors: Kabatereine Narcis B , Standley Claire J , Sousa-Figueiredo Jose C , Fleming Fiona M , Stothard J Russell , Talisuna Ambrose , Fenwick Alan
Published: December 2011

Background

It is widely advocated that integrated strategies for the control of neglected tropical diseases (NTDs) are cost-effective in comparison to vertical disease-specific programmes. A prerequisite for implementation of control interventions is the availability of baseline data of prevalence, including the population at risk and disease overlap. Despite extensive literature on the distribution of schistosomiasis on the mainland in Uganda, there has been a knowledge gap for the prevalence of co-infections with malaria, particularly for island communities in Lake Victoria. In this study, nine lakeshore and island districts were surveyed for the prevalence of NTDs and malaria, as well as educational and health infrastructure.

Results

A total of 203 communities were surveyed, including over 5000 school-age children. Varying levels of existing health infrastructure were observed between districts, with only Jinja District regularly treating people for NTDs. Community medicine distributors (CMD) were identified and trained in drug delivery to strengthen capacity. Prevalence levels of intestinal schistosomiasis and soil-transmitted helminthiasis were assessed via Kato-Katz thick smears of stool and malaria prevalence determined by microscopy of fingerprick blood samples. Prevalence levels were 40.8%, 26.04% and 46.4%, respectively, while the prevalence of co-infection by Schistosoma mansoni and Plasmodium spp. was 23.5%. Socio-economic status was strongly associated as a risk factor for positive infection status with one or more of these diseases.

Conclusions

These results emphasise the challenges of providing wide-scale coverage of health infrastructure and drug distribution in remote lakeshore communities. The data further indicate that co-infections with malaria and NTDs are common, implying that integrated interventions for NTDs and malaria are likely to maximize cost-effectiveness and sustainability of disease control efforts.
Soluble receptor activator of nuclear factor κB ligand/osteoprotegerin ratio is increased in systemic lupus erythematosus patients
Authors: Carmona-Fernandes Diana , Santos Maria José , Perpétuo Inês Pedro , Fonseca João Eurico , Canhão Helena
Published: December 2011

Introduction

Systemic lupus erythematosus (SLE) patients have lower bone mineral density and increased fracture risk when compared with healthy individuals, due to distinct factors and mechanisms. Bone remodeling is a tightly orchestrated process dependent on several factors, including the balance between receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG).

Our aim was to assess serum OPG and soluble RANKL (sRANKL) levels as well as sRANKL/OPG ratio in female SLE patients and compare it with female controls.

Methods

We have evaluated 103 SLE patients and 114 healthy controls, all Caucasian females. All participants underwent a clinical and laboratory evaluation. sRANKL and OPG were quantified in serum by ELISA based methods. sRANKL, OPG and sRANKL/OPG ratio levels were compared between SLE patients and age, sex and race matched healthy controls. For SLE patients, a multivariate analysis was performed, to find the possible predictors of the changes in sRANKL, OPG and sRANKL/OPG ratio levels.

Results

Although sRANKL levels did not differ between the two groups, serum OPG was lower in SLE patients (P < 0.001). This led to an increased sRANKL/OPG ratio (P = 0.010) in the patients' group.

The multivariate analysis was performed considering age and other clinical and laboratorial potential confounders for these variations in the SLE patients group. We have showed that age (P = 0.001) and levels of anti-Sm antibodies (P = 0.016) were independent predictors of sRANKL/OPG ratio variations in SLE patients. No relationship with therapy or disease activity measured by SLEDAI2K was found.

Conclusions

These results are suggestive of increased osteoclastic stimuli driven by the SLE disease mechanisms.
MTRX1011A, a humanized anti-CD4 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a Phase I randomized, double-blind, placebo-controlled study incorporating pharmacodynamic biomarker assessments
Authors: Scheerens Heleen , Su Zheng , Irving Bryan , Townsend Michael J , Zheng Yanan , Stefanich Eric , Chindalore Vishala , Bingham Clifton O , Davis John C
Published: December 2011

Introduction

The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the humanized anti-CD4 monoclonal antibody MTRX1011A in a randomized, double-blind placebo-controlled Phase 1 study in patients with rheumatoid arthritis (RA).

Methods

In the single ascending dose (SAD) portion of the study, patients received single doses of a placebo or MTRX1011A at 0.3, 1.0, 3.5 and 7.0 mg/kg intravenously (IV) or 1.0 and 3.5 mg/kg subcutaneously (SC), followed by five weeks of evaluation. In the multi-dose (MD) portion of the study, placebo or MTRX1011A was administered weekly for eight doses at 1.5 or 3.5 mg/kg SC, or 5 mg/kg IV, followed by eight weeks of evaluation.

Results

MTRX1011A was well tolerated in the SAD phase up to 7 mg/kg IV and in the MD phase up to 1.5 mg/kg SC. At weekly doses of 3.5 mg/kg SC and 5 mg/kg IV, a moderate pruritic papular rash was observed in some MTRX1011A-treated patients, which was considered a dose-limiting toxicity for this clinical indication. No serious adverse events occurred in any cohort. Reduction in disease activity was modest. PD assessments demonstrated that MTRX1011A induced a dose-dependent down-modulation of CD4 expression on peripheral blood CD4 T cells, CD4 receptor occupancy, increases in serum sCD4-MTRX1011A complexes and up-regulation of CD69 on T cells, but was non-depleting.

Conclusions

The maximum tolerated dose of MTRX1011A was 1.5 mg/kg SC administered weekly. At this dose MTRX1011A did not achieve maximum PD activity expected to be required for reduction in disease activity.
Loss of interferon regulatory factor 5 (IRF5) expression in human ductal carcinoma correlates with disease stage and contributes to metastasis
Authors: Bi Xiaohui , Hameed Meera , Mirani Neena , Pimenta Erica Maria , Anari Jason , Barnes Betsy J
Published: December 2011

Introduction

New signaling pathways of the interleukin (IL) family, interferons (IFN) and interferon regulatory factors (IRF) have recently been found within tumor microenvironments and in metastatic sites. Some of these cytokines stimulate while others inhibit breast cancer proliferation and/or invasion. IRFs, a family of nine mammalian transcription factors, have multiple biologic functions that when dysregulated may contribute to tumorigenesis; most well-known are their roles in regulating/initiating host immunity. Some IRF family members have been implicated in tumorigenesis yet little is still known of their expression in primary human tumors or their role(s) in disease development/progression. IRF5 is one of the newer family members to be studied and has been shown to be a critical mediator of host immunity and the cellular response to DNA damage. Here, we examined the expression of IRF5 in primary breast tissue and determined how loss of expression may contribute to breast cancer development and/or progression.

Methods

Formalin-fixed paraffin-embedded archival breast tissue specimens from patients with atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were examined for their expression of IRF1 and IRF5. Knockdown or overexpression of IRF5 in MCF-10A, MCF-7 and MDA-MB-231 mammary epithelial cell lines was used to examine the role of IRF5 in growth inhibition, invasion and tumorigenesis.

Results

Analysis of IRF expression in human breast tissues revealed the unique down-regulation of IRF5 in patients with different grades of DCIS and IDC as compared to IRF1; loss of IRF5 preceded that of IRF1 and correlated with increased invasiveness. Overexpression of IRF5 in breast cancer cells inhibited in vitro and in vivo cell growth and sensitized them to DNA damage. Complementary experiments with IRF5 siRNAs made normal mammary epithelial cells resistant to DNA damage. By 3-D culture, IRF5 overexpression reverted MDA-MB-231 to normal acini-like structures; cells overexpressing IRF5 had decreased CXCR4 expression and were insensitive to SDF-1/CXCL12-induced migration. These findings were confirmed by CXCR4 promoter reporter assays.

Conclusions

IRF5 is an important tumor suppressor that regulates multiple cellular processes involved in the conversion of normal mammary epithelial cells to tumor epithelial cells with metastatic potential.
Breast Cancer Survivors' Perceptions of Survivorship Care Options
Authors: Mayer Erica L. , Gropper Adrienne B. , Neville Bridget A. , Partridge Ann H. , Cameron Danielle B. , Winer Eric P. , Earle Craig C.
Published: December 2011

Purpose

As the number of breast cancer survivors increases, a durable model of comprehensive survivor care is needed, incorporating providers and/or visit types both within and outside of oncology. The objective of this study was to explore survivors' comfort with different clinician types or with a telephone/Internet-based virtual visit as components of survivorship care.

Methods

Breast cancer survivors participating in a general survivorship survey completed an additional breast cancer–specific questionnaire evaluating the self-perceived impact of follow-up visits to various clinician types, or follow-up by a virtual visit, on survival, worrying, and stress related to cancer.

Results

A total of 218 breast cancer survivors completed the questionnaire. Most favored medical oncologist follow-up visits over those with primary care physicians (PCPs) or nurse practitioners (NPs) in terms of reduced worrying about cancer (odds ratio [OR], 2.21; P < .001), reduced stress around the visit (OR, 1.40; P = .002), and improved effect on cancer survival (OR, 2.38; P < .001). However, the majority also displayed substantial comfort with both PCPs and NPs in the same domains. Patients rated a virtual visit as having a less favorable impact on cancer survival and cancer-related worrying compared with in-person visits with clinicians.

Conclusion

Breast cancer survivors are comfortable with both PCPs and NPs providing follow-up care, although they indicate a preference for medical oncologists. Given patients' negative impressions of a virtual visit, increased familiarity with and research investigating this emerging concept are needed. The NP-led survivorship clinic model, with increased guidance for PCPs, offers a promising route for improving quality of and satisfaction with survivor care.
Familial Aggregation of Acute Myeloid Leukemia and Myelodysplastic Syndromes
Authors: Goldin Lynn R. , Kristinsson Sigurdur Y. , Liang Xueying Sharon , Derolf Åsa R. , Landgren Ola , Björkholm Magnus
Published: December 2011

Purpose

Apart from rare pedigrees with multiple cases of acute myeloid leukemia (AML), there is limited data on familial aggregation of AML and myelodysplastic syndromes (MDSs) in the population.

Patients and Methods

Swedish population-based registry data were used to evaluate risk of AML, MDS, and other malignancies among 24,573 first-degree relatives of 6,962 patients with AML and 1,388 patients with MDS compared with 106,224 first-degree relatives of matched controls. We used a marginal survival model to calculate familial aggregation.

Results

AML and/or MDS did not aggregate significantly in relatives of patients with AML. There was a modest risk ratio (RR, 1.3; 95% CI, 0.9 to 1.8) in myeloproliferative/myeloid malignancies combined. The risks for any hematologic or any solid tumor were modestly but significantly increased. Relatives of patients with MDS did not show an increased risk for any hematologic tumors. In contrast, we found a significantly increased risk (RR, 6.5; 95% CI, 1.1 to 38.0) of AML/MDS and of all myeloid malignancies combined (RR, 3.1; 95% CI, 1.0 to 9.8) among relatives of patients diagnosed at younger than age 21 years.

Conclusion

We did not find evidence for familial aggregation of the severe end of the spectrum of myeloid malignancies (AML and MDS). The risks of myeloproliferative neoplasms were modestly increased with trends toward significance, suggesting a possible role of inheritance. In contrast, although limited in sample size, relatives of young patients with AML were at increased risk of AML/MDS, suggesting that germline genes may play a stronger role in these patients. The increased risk of all hematologic malignancies and of solid tumors among relatives of patients with AML suggests that genes for malignancy in general and/or other environmental factors may be shared.
Greece’s Struggle to Escape the Past: A View from Inside
Authors: Miller Thomas J. , Cleverley J. Michael
Published: December 2011

This essay is written from the perspective of inside observers who had regular access to many of the main Greek political and economic players from the era of Andreas Papandreou to the present administration of George Papandreou. One or the other of the authors was working in Greece in senior positions at the US Embassy in Athens with few interruptions from the mid-1980s to the early twenty-first century.
neb: a zebrafish model of nemaline myopathy due to nebulin mutation
Authors: Telfer William R. , Nelson Darcee D. , Waugh Trent , Brooks Susan V. , Dowling James J.
Published: December 2011

Nemaline myopathy is one of the most common and severe non-dystrophic muscle diseases of childhood. Patients typically present in infancy with hypotonia, weakness, delayed motor development, and bulbar and respiratory difficulties. Mutations in six different genes are associated with nemaline myopathy, with nebulin mutations being the most common. No treatments or disease-modifying therapies have been identified for this disease. One of the major barriers to treatment development is the lack of models amenable to rapid and coordinated testing of potential therapeutic strategies. To overcome this barrier, we have characterized the first zebrafish model of nemaline myopathy. This model, termed neb, harbors a recessive mutation in the nebulin gene that results in decreased Nebulin protein levels, a severe motor phenotype and premature lethality. In addition to impaired motor function, neb zebrafish exhibit many of the features associated with human nemaline myopathy. These include impaired force generation, altered thin filament length and the presence of specific histopathological changes, including the formation of nemaline bodies. In summary, neb zebrafish mirror the genetic, clinical and pathological aspects of nemaline myopathy due to NEB mutation, and thus are an excellent model for future therapy development for this devastating disorder.
Endogenous Information Flows and the Clustering of Announcements
Authors: Acharya Viral V , DeMarzo Peter , Kremer Ilan
Published: December 2011

We consider the strategic timing of information releases in a dynamic disclosure model. Because investors don't know whether or when the firm is informed, the firm will not necessarily disclose immediately. We show that bad market news can trigger the immediate release of information by firms. Conversely, good market news slows the release of information by firms. Thus, our model generates clustering of negative announcements. Surprisingly, this result holds only when firms can preemptively disclose their own information prior to the arrival of external information. These results have implications for conditional variance and skewness of stock returns. (JEL D21, D83, G12, G14, L11)
Buffalo Hunt: International Trade and the Virtual Extinction of the North American Bison
Authors: Taylor M. Scott
Published: December 2011

In the sixteenth century, North America contained 25 to 30 million buffalo; by the late nineteenth century fewer than 100 remained. While removing the buffalo east of the Mississippi took over 100 years, the remaining 10 to 15 million buffalo on the Great Plains were killed in a punctuated slaughter lasting little more than ten years. I employ theory, international trade statistics, and first-person accounts to argue the slaughter was initiated by a foreign-made innovation and fueled by a foreign demand for industrial leather. European demand and American policy failure are jointly responsible for the “Slaughter on the Plains.” (JEL F14, N51, N71, Q57)
Extreme Walrasian Dynamics: The Gale Example in the Lab
Authors: Crockett Sean , Oprea Ryan , Plott Charles
Published: December 2011

We study David Gale's (1963) economy using laboratory markets. Tatonnement theory predicts prices will diverge from an equitable interior equilibrium toward infinity or zero depending only on initial prices. The inequitable equilibria determined by these dynamics give all gains from exchange to one side of the market. We show surprisingly strong support for these predictions. In most sessions one side of the market eventually outgains the other by more than 20 times, leaving the disadvantaged side to trade for mere pennies. We also find preliminary evidence that these dynamics are sticky, resisting exogenous interventions designed to reverse their trajectories. (JEL C92, D50)
Media and Political Persuasion: Evidence from Russia
Authors: Enikolopov Ruben , Petrova Maria , Zhuravskaya Ekaterina
Published: December 2011

This paper compares electoral outcomes of 1999 parliamentary elections in Russia among geographical areas with differential access to the only national TV channel independent from the government. It was available to three-quarters of Russia's population and its signal availability was idiosyncratic, conditional on observables. Independent TV decreased aggregate vote for the government party by 8.9 percentage points, increased the combined vote for major opposition parties by 6.3 percentage points, and decreased turnout by 3.8 percentage points. The probability of voting for opposition parties increased for individuals who watched independent TV even controlling for voting intentions measured one month before elections. (JEL D72, L82, P26)
Relative Earnings and Giving in a Real-Effort Experiment
Authors: Erkal Nisvan , Gangadharan Lata , Nikiforakis Nikos
Published: December 2011

This paper investigates the relationship between relative earnings and giving in a two-stage, real-effort experiment. In the first stage, four players compete in a tournament that determines their earnings. In the second stage, they decide whether to make a transfer to one or more of their group members. Our main finding is that those ranked first are significantly less likely to give than those ranked second. This difference disappears if individuals learn about the second stage after earning their income or if earnings are randomly determined. This suggests that our main finding is driven by selection based on other-regarding preferences. JEL: D64, J31