bluuebunny/crossref_metadata_2025 huggingface dataset:
Research progress in wood-plastic nanocomposites
Authors: Turku Irina , Kärki Timo
Published: May 2013

The interest towards wood-plastic composites (WPCs) is growing due to growing interest in materials with novel properties, which can replace more traditional materials, such as wood and plastic. The use of recycled materials in manufacture is also a bonus. However, the application of WPCs has been limited because of their often poor mechanical and barrier properties, which can be improved by incorporation of the reinforcing fillers. Nano-sized fillers, having a large surface area, can significantly increase interfacial interactions in the composite on molecular level, leading to materials with new properties. The review summarizes the development trends in the use on nanofillers for WPC design, which were reported in accessible literature during the last decade. The effect of the nanofillers on the mechanical properties, thermal stability, flammability and wettability of WPC is discussed.
Occupational sex-segregation, specialized human capital and wages: evidence from Britain
Authors: Perales Francisco
Published: May 2013

Female-dominated occupations are poorly paid, but there is disagreement about why. Sociological explanations argue that pay in such occupations is low because society undervalues ‘women’s work’, while economic theory argues that this is due to scant requirements for specialized skills. This article sheds light over these debates by examining the impact of occupational feminization on wages in Britain and exploring the mechanisms that produce it, using innovative statistical models that account for both observable and unobservable skill. Results confirm that occupational sex-segregation explains a sizeable portion of the gender wage gap and that wages in female-dominated occupations are lower than wages in other occupations. Inconsistent with human capital theory, low pay in female-dominated occupations cannot be explained fully by low skill specialization or by observable or unobservable characteristics of their workers. Remaining wage penalties in such occupations are consequently taken as evidence of institutional devaluation of ‘women’s work’.
Methodological implications of Marxist practical philosophy for psychology: A perspective from China
Authors: Yang Wendeng , Ye Haosheng
Published: May 2013

One of the traditional branches of Western practical philosophy, Marxist practical philosophy, is still the mainstream philosophy in contemporary China. It provides not only a new understanding of human nature, mind, behavior, and environment, but also an alternative perspective for the study of psychology. It is from this perspective that activity theory in the former Soviet Union and “practice” discussions in China try to integrate Marxist practical philosophy with psychology. Based on these attempts, we advocate the introduction of “practice” into psychology and the understanding of all psychological problems as starting from “practice.” First, “practice” is defined as people’s creative activity and a way of human existence. The structure of “practice” is then divided into three hierarchies: reflexive practice, cognitive practice, and social and cultural practice. Finally, two examples are chosen to explain how to research psychology from the viewpoint of Marxist practical philosophy.
Lights, Camera, Action! Learning About Management With Student-Produced Video Assignments
Authors: Schultz Patrick L. , Quinn Andrew S.
Published: May 2013

In this article, we present a proposal for fostering learning in the management classroom through the use of student-produced video assignments. We describe the potential for video technology to create active learning environments focused on problem solving, authentic and direct experiences, and interaction and collaboration to promote student learning. We argue for the use of a student-produced video assignment as a way to achieve these outcomes and present an adaptation of a project known as the Newsroom Assignment. We present details on how instructors can implement the assignment, with suggestions for future research on the use of student-produced video projects in management courses.
What Trust Matters When
Authors: Alexopoulos Angelos N. , Buckley Finian
Published: May 2013

While trusting coworker relationships are conducive to knowledge transfer, distinct types of trust and the contextual conditions under which they are most effective have received limited empirical attention. In this article, we distinguish between professional and personal trust, and hypothesize that their relative knowledge transfer advantage may vary as a function of the duration of the receiver-source relationship. Using survey data from 135 knowledge receivers reporting on their relationships with their knowledge sources, we find that both professional and personal trust interact with relationship duration, albeit in opposite directions. We also find a synergistic effect of the two types of trust on knowledge transfer but only in long duration relationships. The implications of distinguishing professional and personal trust within the overall nomological network of trust are discussed in terms of theory and practice development.
The intersectional turn in feminist theory: A dream of a common language?
Authors: Carbin Maria , Edenheim Sara
Published: May 2013

Today intersectionality has expanded from being primarily a metaphor within structuralist feminist research to an all-encompassing theory. This article discusses this increasing dedication to intersectionality in European feminist research. How come intersectionality has developed into a signifier for ‘good feminist research’ at this particular point in time? Drawing on poststructuralist and postcolonial theory the authors examine key articles on intersectionality as well as special issues devoted to the concept. They interrogate the conflicts and meaning making processes as well as the genealogies of the concept. Thus, the epistemology and ontology behind the ‘intersectional turn’ in feminist theory is the main concern here. The authors argue that the lack of ontological discussions has lead to its very popularity. Intersectionality promises almost everything: to provide complexity, overcome divisions and to serve as a critical tool. However, the expansion of the scope of intersectionality has created a consensus that conceals fruitful and necessary conflicts within feminism.
Epistemic autonomy: A criterion for virtue?
Authors: Mudd Sasha
Published: May 2013

Catherine Elgin proposes a novel principle for identifying epistemic virtue. Based loosely on Kant’s Categorical Imperative, it identifies autonomy as our fundamental epistemic responsibility, and defines the epistemic virtues as those traits of character needed to exercise epistemic autonomy. I argue that Elgin’s principle fails as a criterion of epistemic virtue because the instrumental conception of autonomy on which it relies leads to an untenable relativism. Despite this, I suggest that autonomy may yet furnish a plausible criterion for epistemic virtue, provided we construe autonomy as Kant does, as grounded in categorical rather than instrumental reason.
Eliminating Tobacco-Related Disparities Among Pacific Islanders Through Leadership and Capacity Building
Authors: David Annette M. , Lew Rod , Lyman Annabel K. , Otto Caleb , Robles Rebecca , Cruz George J.
Published: May 2013

Tobacco remains a major risk factor for premature death and ill health among Pacific Islanders, and tobacco-related disparities persist. Eliminating these disparities requires a comprehensive approach to transform community norms about tobacco use through policy change, as contained in the World Health Organization international Framework Convention on Tobacco Control. Three of the six U.S.-affiliated Pacific Islands—the Federated States of Micronesia, Palau, and the Marshall Islands—are Parties to the Framework; the remaining three territories—American Samoa, the Commonwealth of the Northern Mariana Islands, and Guam—are excluded from the treaty by virtue of U.S. nonratification. Capacity building and leadership development are essential in achieving policy change and health equity within Pacific Islander communities. We describe promising practices from American Samoa, the Commonwealth of the Northern Mariana Islands, the Federated States of Micronesia, Guam, and Palau and highlight some of the key lessons learned in supporting and sustaining the reduction in tobacco use among Pacific Islanders as the first step toward eliminating tobacco-related disparities in these populations.
Writing the Torment
Authors: Bridges-Rhoads Sarah , Van Cleave Jessica
Published: May 2013

In this article, we reconfigure the notion of writing with theory to include a troubling of theory as data that is always already coded by our citational practices. However, the reduction of the “cacophony of ideas swirling as we think about our topics with all we can muster” to a singular citation, while necessary if we want to bear the burden of our interpretations, is also dangerous because the more mechanistic data analysis becomes, the less situated it is. We demonstrate here how we rupture this mechanistic bent by using the space of the page both to inhabit and halt aporias, producing aporetic data. When we write and reread our claims to those theorists through citation, aporetic data highlights our inability to do those theorists justice and produces additional uncertainty about the possibility of justice for any data. To that end, we provide a theoretical conversation that has been interrupted and revisited multiple times as we think and rethink the many Derridas produced through our readings. This work highlights the possibilities enabled by calling upon one another to keep data in motion by truncating, diverting, or extending aporias rather than treating data as passive objects.
Drug-related falls in older patients: implicated drugs, consequences, and possible prevention strategies
Authors: de Jong Marlies R. , Van der Elst Maarten , Hartholt Klaas A.
Published: May 2013

Falls are the leading cause of injuries among older adults, aged 65 years and older. Furthermore, falls are an increasing public health problem because of ageing populations worldwide due to an increase in the number of older adults, and an increase in life expectancy. Numerous studies have identified risk factors and investigated possible strategies to prevent (recurrent) falls in community-dwelling older people and those living in long-term care facilities. Several types of drugs have been associated with an increased fall risk. Since drugs are a modifiable risk factor, periodic drug review among older adults should be incorporated in a fall prevention programme.
Notch1 regulates angio-supportive bone marrow–derived cells in mice: relevance to chemoresistance
Authors: Roodhart Jeanine M. L. , He Huanhuan , Daenen Laura G. M. , Monvoisin Arnaud , Barber Chad L. , van Amersfoort Miranda , Hofmann Jennifer J. , Radtke Freddy , Lane Timothy F. , Voest Emile E. , Iruela-Arispe M. Luisa
Published: May 2013

Key Points

Exposure to chemotherapy promotes the exit of specific subpopulations of BMDCs with angio-supportive activity. Notch in BMDCs is required for the exit of these cells from the bone marrow and for chemotherapy-enhanced angiogenesis in tumors.
Characterisation of the potential function of SVA retrotransposons to modulate gene expression patterns
Authors: Savage Abigail L , Bubb Vivien J , Breen Gerome , Quinn John P
Published: May 2013

Background

Retrotransposons are a major component of the human genome constituting as much as 45%. The hominid specific SINE-VNTR-Alus are the youngest of these elements constituting 0.13% of the genome; they are therefore a practical and amenable group for analysis of both their global integration, polymorphic variation and their potential contribution to modulation of genome regulation.

Results

Consistent with insertion into active chromatin we have determined that SVAs are more prevalent in genic regions compared to gene deserts. The consequence of which, is that their integration has greater potential to have affects on gene regulation. The sequences of SVAs show potential for the formation of secondary structure including G-quadruplex DNA. We have shown that the human specific SVA subtypes (E-F1) show the greatest potential for forming G-quadruplexes within the central tandem repeat component in addition to the 5’ ‘CCCTCT’ hexamer. We undertook a detailed analysis of thePARK7SVA D, located in the promoter of thePARK7gene (also termedDJ-1), in a HapMap cohort where we identified 2 variable number tandem repeat domains and 1 tandem repeat within this SVA with the 5’ CCCTCT element being one of the variable regions. Functionally we were able to demonstrate that this SVA contains multiple regulatory elements that support reporter gene expressionin vitroand further show these elements exhibit orientation dependency.

Conclusions

Our data supports the hypothesis that SVAs integrate preferentially in to open chromatin where they could modify the existing transcriptional regulatory domains or alter expression patterns by a variety of mechanisms.
Predictors of suicidal behaviour in 36,304 individuals sickness absent due to stress-related mental disorders - a Swedish register linkage cohort study
Authors: Ishtiak-Ahmed Kazi , Perski Aleksander , Mittendorfer-Rutz Ellenor
Published: May 2013

Background

Stress-related mental disorders (SRMD), which correspond to the diagnostic code F43 in the International Classification of Diseases, version 10, rank among the leading causes of sickness absence in several European countries. Despite the size of this health problem, research on risk factors for severe medical outcomes, like suicidal behavior, is lacking to date. The aim of this study was to investigate predictors of suicide attempt and suicide among sickness absentees with SRMD.

Methods

A cohort of 36,304 non-retired individuals, aged 16–64 years on 31.12.2004, with at least one sickness absence spell due to SRMD, initiated in 2005, was followed up with regard to suicide attempt (2006–2009) and suicide (2006–2008). Univariate and multivariate hazard ratios (HR) with 95% confidence intervals (CI) were estimated for a number of predictors.

Results

During the follow-up period, 266 individuals attempted suicide and 34 committed suicide. In the multivariate analyses, the following factors increased the risk of suicide attempt: =< 25 years of age, low educational level, lone parenthood, > 1 sickness absence spell, long duration of the first spell of sickness absence due to SRMD (> 180 days), > 4 and > 8 days of inpatient care due to somatic or mental diagnoses (2000–2005), and > 4 and > 1 outpatient visits due to somatic or mental diagnoses (2001–2005), respectively. Hazard ratios ranged from 1.4 to 4.2. Health care due to mental diagnoses and > 1 spell of sickness absence regardless of diagnosis were predictive of suicide.

Conclusions

Several predictors related to socio-demographics, sickness absence and health-care consumption were identified as risk factors for suicidal behavior. Consideration of these risk factors is of both clinical and public health importance.
In situ magnetic separation of antibody fragments from Escherichia coli in complex media
Authors: Cerff Martin , Scholz Alexander , Franzreb Matthias , Batalha Iris L , Roque Ana Cecilia A , Posten Clemens
Published: May 2013

Background

In situ magnetic separation (ISMS) has emerged as a powerful tool to overcome process constraints such as product degradation or inhibition of target production. In the present work, an integrated ISMS process was established for the production of his-tagged single chain fragment variable (scFv) D1.3 antibodies (“D1.3”) produced by E. coli in complex media. This study investigates the impact of ISMS on the overall product yield as well as its biocompatibility with the bioprocess when metal-chelate and triazine-functionalized magnetic beads were used.

Results

Both particle systems are well suited for separation of D1.3 during cultivation. While the triazine beads did not negatively impact the bioprocess, the application of metal-chelate particles caused leakage of divalent copper ions in the medium. After the ISMS step, elevated copper concentrations above 120 mg/L in the medium negatively influenced D1.3 production. Due to the stable nature of the model protein scFv D1.3 in the biosuspension, the application of ISMS could not increase the overall D1.3 yield as was shown by simulation and experiments.

Conclusions

We could demonstrate that triazine-functionalized beads are a suitable low-cost alternative to selectively adsorb D1.3 fragments, and measured maximum loads of 0.08 g D1.3 per g of beads. Although copper-loaded metal-chelate beads did adsorb his-tagged D1.3 well during cultivation, this particle system must be optimized by minimizing metal leakage from the beads in order to avoid negative inhibitory effects on growth of the microorganisms and target production. Hereby, other types of metal chelate complexes should be tested to demonstrate biocompatibility. Such optimized particle systems can be regarded as ISMS platform technology, especially for the production of antibodies and their fragments with low stability in the medium. The proposed model can be applied to design future ISMS experiments in order to maximize the overall product yield while the amount of particles being used is minimized as well as the number of required ISMS steps.
Water extract of Spatholobus suberectus inhibits osteoclast differentiation and bone resorption
Authors: Ha Hyunil , Shim Ki-Shuk , An Hyosun , Kim Taesoo , Ma Jin Yeul
Published: May 2013

Background

Osteoclasts are primarily responsible for bone resorption. In many pathological bone diseases including osteoporosis and rheumatoid arthritis, osteoclasts are excessively activated. Thus, controlling of osteoclasts would be an effective therapeutic strategy for the treatment of excessive bone loss. The stem of Spatholobus suberectus has been widely used in traditional medicine to treat blood stasis syndrome and arthritis in Asia. In the present study, we investigated the effects and action mechanism of water extract of the stem of Spatholobus suberectus (WESS) on osteoclast differentiation and function.

Methods

The effect of WESS on osteoclast differentiation was evaluated by counting tartrate resistant acid phosphatase-positive multinucleated cells in bone marrow-derived macrophages system and murine bone marrow cell-osteoblast coculture system. Bone resorption activity of mature osteoclast was examined on a calcium phosphate-coated plate. Actin ring structure of osteoclasts was detected fluorescently by staining for F-actin. Activation of signaling pathways and induction of transcription factors required for osteoclastogenesis were investigated by real-time PCR and Western blotting.

Results

WESS effectively inhibited osteoclast differentiation from its precursors. The inhibitory effect of WESS on osteoclast differentiation was due to the suppression of osteoclastogenic transcription factors, c-Fos and nuclear factor of activated T cells cytoplasmic 1 expression, via preventing receptor activator of nuclear factor-κB ligand-induced early signaling pathways and decreasing c-Fos protein level in osteoclast precursors. Furthermore, WESS suppressed bone resorption activity of osteoclasts by disrupting actin ring structure.

Conclusions

This study demonstrated that WESS inhibits osteoclast differentiation and function. These results suggest that WESS has a potential for treating pathological bone diseases caused by excessive bone resorption.
Application of propensity scores to estimate the association between government subsidy and injection use in primary health care institutions in China
Authors: Tang Yuqing , Zhang Xiaopeng , Yang Chunyan , Yang Lianping , Wang Hongtao , Zhang Xinping
Published: May 2013

Background

The problem posed by therapeutic injection is a clinical practice issue that influences health care quality and patient safety. Although sufficient government subsidy was one of the 12 key interventions to promote rational drug use initiated by WHO (World Health Organization), limited information is available about the association between government subsidy and injection use in primary health care institutions. In 2009, National Essential Medicines System (NEMS) was implemented in China. The subsidy policy plays an important role in maintaining primary health care institutions. This study explores the impact of government subsidies on the injection use in primary health care institutions in China.

Methods

126 primary health institutions were included in this study. Institutions were divided into two groups (intervention and control groups) according to the median GS (General subsidy per personnel). Propensity score matching (PSM) was used to minimize the observed covariate differences in the characteristics of the primary institutions between the two groups. Kappa score was calculated to determine the consistency between the groups. Paired chi-square test and Relative Risk (RR) were calculated to compare the differences in injection use between the groups.

Results

Among all the investigated prescriptions, the overall percent of people who received an injection prescribed was 36.96% (n = 12600). PSM showed no significant covariate difference among the 34 groups obtained through this analysis. Kappa score (k = −0.082, p = 0.558) indicated an inconsistency between groups and paired chi-square test revealed a significant difference (p < 0.05) in injection use between the two groups. Relative Risk = 0.679 (95%CI [0.485, 0.950]) indicate that high General subsidy per personnel is a protective factor for primary health care institutions to prescribe injections properly. The intervention group obtained a higher possibility of using injection properly.

Conclusions

The overall effect of government subsidy on the use of injection was positively significant. However, the mechanism by which government subsidy influence injection administration remains unclear, and thus requires further study.
Polymorphism of the parasite lactate dehydrogenase gene from Plasmodium vivax Korean isolates
Authors: Shin Hyun-Il , Kim Jung-Yeon , Lee Won-Ja , Sohn Youngjoo , Lee Sang-Wook , Kang Yoon-Joong , Lee Hyeong-Woo
Published: May 2013

Background

Assaying for the parasitic lactate dehydrogenase (pLDH) is widely used as a rapid diagnostic test (RDT), but the efficacy of its serological effectiveness in diagnosis, that is antibody detection ability, is not known. The genetic variation of Korean isolates was analysed, and recombinant protein pLDH was evaluated as a serodiagnostic antigen for the detection of Plasmodium vivax malaria.

Methods

Genomic DNA was purified, and the pLDH gene of P. vivax was amplified from blood samples from 20 patients. The samples came from five epidemic areas: Bucheon-si, Gimpo-si, and Paju-si of Gyeonggi Province, Gangwha-gun of Incheon metropolitan city, and Cheorwon-gun of Gangwon Province, South Korea, from 2010 to 2011. The antigenicity of the recombinant protein pLDH was tested by western blot and enzyme-linked immunosorbent assay (ELISA).

Results

Sequence analysis of 20 Korean isolates of P. vivax showed that the open reading frame (ORF) of 951 nucleotides encoded a deduced protein of 316 amino acids (aa). This ORF showed 100% identity with the P. vivax Belem strain (DQ060151) and P. vivax Hainan strain (FJ527750), 89.6% homology with Plasmodium falciparum FCC1_HN (DQ825436), 90.2% homology with Plasmodium berghei (AY437808), 96.8% homology with Plasmodium knowlesi (JF958130), and 90.2% homology with Plasmodium reichenowi (AB122147). A single-nucleotide polymorphism (SNP) at nucleotide 456 (T to C) was also observed in the isolate from Bucheon, but it did not change in the amino acid sequence. The expressed recombinant protein had a molecular weight of approximately 32 kDa, as analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. Of the 40 P. vivax patients, 34 (85.0%) were positive by ELISA.

Conclusions

The pLDH genes of 19 isolates of P. vivax were identical, except one for SNP at nucleotide 456. This observation indicates that this gene is relatively stable. Based on these results, the relationship between antibody production against pLDH and the pattern of disease onset should be investigated further before using pLDH for serodiagnosis.
Activation of Akt pathway by transcription-independent mechanisms of retinoic acid promotes survival and invasion in lung cancer cells
Authors: García-Regalado Alejandro , Vargas Miguel , García-Carrancá Alejandro , Aréchaga-Ocampo Elena , González-De la Rosa Claudia Haydée
Published: May 2013

Background

All-trans retinoic acid (ATRA) is currently being used in clinical trials for cancer treatment. The use of ATRA is limited because some cancers, such as lung cancer, show resistance to treatment. However, little is known about the molecular mechanisms that regulate resistance to ATRA treatment. Akt is a kinase that plays a key role in cell survival and cell invasion. Akt is often activated in lung cancer, suggesting its participation in resistance to chemotherapy. In this study, we explored the hypothesis that activation of the Akt pathway promotes resistance to ATRA treatment at the inhibition of cell survival and invasion in lung cancer. We aimed to provide guidelines for the proper use of ATRA in clinical trials and to elucidate basic biological mechanisms of resistance.

Results

We performed experiments using the A549 human lung adenocarcinoma cell line. We found that ATRA treatment promotes PI3k-Akt pathway activation through transcription-independent mechanisms. Interestingly, ATRA treatment induces the translocation of RARα to the plasma membrane, where it colocalizes with Akt. Immunoprecipitation assays showed that ATRA promotes Akt activation mediated by RARα-Akt interaction. Activation of the PI3k-Akt pathway by ATRA promotes invasion through Rac-GTPase, whereas pretreatment with 15e (PI3k inhibitor) or over-expression of the inactive form of Akt blocks ATRA-induced invasion. We also found that treatment with ATRA induces cell survival, which is inhibited by 15e or over-expression of an inactive form of Akt, through a subsequent increase in the levels of the active form of caspase-3. Finally, we showed that over-expression of the active form of Akt significantly decreases expression levels of the tumor suppressors RARβ2 and p53. In contrast, over-expression of the inactive form of Akt restores RARβ2 expression in cells treated with ATRA, indicating that activation of the PI3k-Akt pathway inhibits the expression of ATRA target genes.

Conclusion

Our results demonstrate that rapid activation of Akt blocks transcription-dependent mechanism of ATRA, promotes invasion and cell survival and confers resistance to retinoic acid treatment in lung cancer cells. These findings provide an incentive for the design and clinical testing of treatment regimens that combine ATRA and PI3k inhibitors for lung cancer treatment.
Depletion of polycistronic transcripts using short interfering RNAs: cDNA synthesis method affects levels of non-targeted genes determined by quantitative PCR
Authors: Hanning Jennifer E , Groves Ian J , Pett Mark R , Coleman Nicholas
Published: May 2013

Background

Short interfering RNAs (siRNAs) are often used to deplete viral polycistronic transcripts, such as those encoded by human papillomavirus (HPV). There are conflicting data in the literature concerning how siRNAs targeting one HPV gene can affect levels of other genes in the polycistronic transcripts. We hypothesised that the conflict might be partly explained by the method of cDNA synthesis used prior to transcript quantification.

Findings

We treated HPV16-positive cervical keratinocytes with siRNAs targeting the HPV16 E7 gene and used quantitative PCR to compare transcript levels of E7 with those of E6 and E2, viral genes located upstream and downstream of the target site respectively. We compared our findings from cDNA generated using oligo-dT primers alone with those from cDNA generated using a combination of random hexamer and oligo-dT primers. Our data show that when polycistronic transcripts are targeted by siRNAs, there is a period when untranslatable cleaved mRNA upstream of the siRNA binding site remains detectable by PCR, if cDNA is generated using random hexamer primers. Such false indications of mRNA abundance are avoided using oligo-dT primers. The period corresponds to the time taken for siRNA activity and degradation of the cleaved transcripts. Genes downstream of the siRNA binding site are detectable during this interval, regardless of how the cDNA is generated.

Conclusions

These data emphasise the importance of the cDNA synthesis method used when measuring transcript abundance following siRNA depletion of polycistronic transcripts. They provide a partial explanation for erroneous reports suggesting that siRNAs targeting HPV E7 can have gene-specific effects.
Chlamydia felis exposure in companion dogs and cats in Lanzhou, China: a public health concern
Authors: Wu Song-Ming , Huang Si-Yang , Xu Min-Jun , Zhou Dong-Hui , Song Hui-Qun , Zhu Xing-Quan
Published: May 2013

Background

Chlamydiaceae is a family of obligate intracellular pathogens with a worldwide distribution in many animal species, including humans. No information exists on the prevalence of Chlamydia felis infections in cats and dogs in Lanzhou, the geographical center of China. The aim of this study was to carry out a census of cats and dogs in Lanzhou and document the seroprevalence of C. felis exposure in these companion animals.

Results

In this study, blood samples were collected from 485 animals (221 cats and 264 pet dogs) in Lanzhou between November 2010 and July 2011 to identify antibodies against C. felis. Thirteen of 221 (5.9%) cats and 32 of 264 (12.1%) pet dogs were positive for C. felis infection using indirect hemagglutination at a cutoff of 1:16. The seroprevalence in household and stray cats was 3.9% and 14.3%, respectively, and the difference was statistically significant (P < 0.05). Among different age groups, the seroprevalence in cats varied from 1.9 to 7.9%, and that in dogs ranged from 9.6 to 20.4%; however, the differences were not statistically significant (P > 0.05).

Conclusions

This is the first report of the seroprevalence of C. felis exposure in cats and dogs in Lanzhou, northwestern China. Our results indicate that the presence of C. felis exposure in cats and dogs may pose a potential threat to human health.
Olmsted syndrome: exploration of the immunological phenotype
Authors: Danso-Abeam Dina , Zhang Jianguo , Dooley James , Staats Kim A , Van Eyck Lien , Van Brussel Thomas , Zaman Shari , Hauben Esther , Van de Velde Marc , Morren Marie-Anne , Renard Marleen , Van Geet Christel , Schaballie Heidi , Lambrechts Diether , Tao Jinsheng , Franckaert Dean , Humblet-Baron Stephanie , Meyts Isabelle , Liston Adrian
Published: May 2013

Background

Olmsted syndrome is a rare congenital skin disorder presenting with periorifical hyperkeratotic lesions and mutilating palmoplantar keratoderma, which is often associated with infections of the keratotic area. A recent study identified de novo mutations causing constitutive activation of TRPV3 as a cause of the keratotic manifestations of Olmsted syndrome.

Methods

Genetic, clinical and immunological profiling was performed on a case study patient with the clinical diagnosis of Olmsted syndrome.

Results

The patient was found to harbour a previously undescribed 1718G-C transversion in TRPV3, causing a G573A point mutation. In depth clinical and immunological analysis found multiple indicators of immune dysregulation, including frequent dermal infections, inflammatory infiltrate in the affected skin, hyper IgE production and elevated follicular T cells and eosinophils in the peripheral blood.

Conclusions

These results provide the first comprehensive assessment of the immunological features of Olmsted syndrome. The systemic phenotype of hyper IgE and persistent eosinophilia suggest a primary or secondary role of immunological processes in the pathogenesis of Olmsted syndrome, and have important clinical consequences with regard to the treatment of Olmsted syndrome patients.
ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response
Authors: Umemori Juzoh , Takao Keizo , Koshimizu Hisatsugu , Hattori Satoko , Furuse Tamio , Wakana Shigeharu , Miyakawa Tsuyoshi
Published: May 2013

Background

The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. Grin1 is a candidate susceptibility gene for neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). In our previous study, we examined an N-ethyl-N-nitrosourea (ENU)-generated mutant mouse strain (Grin1
Rgsc174/Grin1
+) that has a non-synonymous mutation in Grin1. These mutant mice showed hyperactivity, increased novelty-seeking to objects, and abnormal social interactions. Therefore, Grin1
Rgsc174/Grin1
+ mice may serve as a potential animal model of neuropsychiatric disorders. However, other behavioral characteristics related to these disorders, such as working memory function and sensorimotor gating, have not been fully explored in these mutant mice. In this study, to further investigate the behavioral phenotypes of Grin1
Rgsc174/Grin1
+ mice, we subjected them to a comprehensive battery of behavioral tests.

Results

There was no significant difference in nociception between Grin1
Rgsc174/Grin1
+ and wild-type mice. The mutants did not display any abnormalities in the Porsolt forced swim and tail suspension tests. We confirmed the previous observations that the locomotor activity of these mutant mice increased in the open field and home cage activity tests. They displayed abnormal anxiety-like behaviors in the light/dark transition and the elevated plus maze tests. Both contextual and cued fear memory were severely deficient in the fear conditioning test. The mutant mice exhibited slightly impaired working memory in the eight-arm radial maze test. The startle amplitude was markedly decreased in Grin1
Rgsc174/Grin1
+ mice, whereas no significant differences between genotypes were detected in the prepulse inhibition (PPI) test. The mutant mice showed no obvious deficits in social behaviors in three different social interaction tests.

Conclusions

This study demonstrated that the Grin1
Rgsc174/Grin1
+ mutation causes abnormal anxiety-like behaviors, a deficiency in fear memory, and a decreased startle amplitude in mice. Although Grin1
Rgsc174/Grin1
+ mice only partially recapitulate symptoms of patients with ADHD, schizophrenia, and bipolar disorder, they may serve as a unique animal model of a certain subpopulation of patients with these disorders.
Delta-like 1 regulates Bergmann glial monolayer formation during cerebellar development
Authors: Hiraoka Yuichi , Komine Okiru , Nagaoka Mai , Bai Ning , Hozumi Katsuto , Tanaka Kohichi
Published: May 2013

Background

Bergmann glia (BG) are unipolar cerebellar astrocytes. The somata of mature BG reside in the Purkinje cell layer and extend radially arranged processes to the pial surface. BG have multiple branched processes, which enwrap the synapses of Purkinje cell dendrites. They migrate from the ventricular zone and align next to the Purkinje cell layer during development. Previously, we reported that Notch1, Notch2, and RBPj genes in the BG play crucial roles in the monolayer formation and morphogenesis of BG. However, it remains to be determined which ligand activates Nocth1 and Notch 2 on BG. Delta-like 1 (Dll1) is a major ligand of Notch receptors that is expressed in the developing cerebellum.

Results

In this study, we used human glial fibrillary acidic protein (hGFAP) promoter-driven Cre-mediated recombination to delete Dll1 in BG. Dll1-conditional mutant mice showed disorganization of Bergmann fibers, ectopic localization of BG in the molecular layer and a reduction in the number of BG.

Conclusion

These results suggest that Dll1 is required for the formation of the BG layer and its morphological maturation, apparently through a Notch1/2-RBPj dependent signaling pathway.
ZBTB33 binds unmethylated regions of the genome associated with actively expressed genes
Authors: Blattler Adam , Yao Lijing , Wang Yao , Ye Zhenqing , Jin Victor X , Farnham Peggy J
Published: May 2013

Background

DNA methylation and repressive histone modifications cooperate to silence promoters. One mechanism by which regions of methylated DNA could acquire repressive histone modifications is via methyl DNA-binding transcription factors. The zinc finger protein ZBTB33 (also known as Kaiso) has been shown in vitro to bind preferentially to methylated DNA and to interact with the SMRT/NCoR histone deacetylase complexes. We have performed bioinformatic analyses of Kaiso ChIP-seq and DNA methylation datasets to test a model whereby binding of Kaiso to methylated CpGs leads to loss of acetylated histones at target promoters.

Results

Our results suggest that, contrary to expectations, Kaiso does not bind to methylated DNA in vivo but instead binds to highly active promoters that are marked with high levels of acetylated histones. In addition, our studies suggest that DNA methylation and nucleosome occupancy patterns restrict access of Kaiso to potential binding sites and influence cell type-specific binding.

Conclusions

We propose a new model for the genome-wide binding and function of Kaiso whereby Kaiso binds to unmethylated regulatory regions and contributes to the active state of target promoters.
Use of a Low-fidelity simulator to improve trans-nasal fibre-optic flexible laryngoscopy in the clinical setting: A randomized, single-blinded, prospective study
Authors: Deutschmann Michael W , Yunker Warren K , Cho John J , Andreassen Meri , Beveridge Shari , Bosch John Douglas
Published: May 2013

Background

Trans-nasal flexible fibre-optic laryngoscopy (TFFL) is an essential skill for otolaryngologists. There is evidence to suggest that simulators help residents acquire procedural skills. The objective of this study was to examine the effect of simulation on endoscopy skill acquistion.

Methods

A randomized controlled trial was conducted utilizing medical students and junior residents with limited experience in TFFL. Learners all performed a baseline endoscopy and were then randomized to receive either 45 minutes of simulation training or not. Following this, a second endoscopy was performed. Time to adequate visualization of the glottis, the percentage of time adequate visualization of the airway was maintained, and the number of collisions with mucosa were analyzed. Qualitative assessments were also obtained from the learner, patient, and staff laryngologist.

Results

Time to adequate visualization of the glottis and the number of mucosal collisions were significantly less during the second endoscopy, irrespective of the use of simulation (84.8 sec vs. 68 sec, p < 0.01; 5.0 vs. 3.2, p < 0.01, respectively). Analysis using a two-way ANOVA with interaction established that none of the quantitative measures analyzed in this study improved with the addition of simulation.

Conclusion

Improvements in time to visualization of the glottis and number of mucosal contacts were seen between the first and second endoscopy irrespective of simulator use. No additional benefit was conferred with the use of a low-fidelity simulator.
Does vasopressor therapy have an indication in hemorrhagic shock?
Authors: Beloncle François , Meziani Ferhat , Lerolle Nicolas , Radermacher Peter , Asfar Pierre
Published: May 2013

This review aimed to answer whether the vasopressors are useful at the early phase of hemorrhagic shock. Data were taken from published experimental studies and clinical trials. Published case reports were discarded. A search of electronic database PubMed was conducted using keywords of hemorrhagic shock, vasopressors, vasoconstrictors, norepinephrine, epinephrine, vasopressin. The redundant papers were not included. We identified 15 experimental studies that compared hemorrhagic shock resuscitated with or without vasopressors, three retrospective clinical studies, and one controlled trial. The experimental and clinical studies are discussed in the clinical context, and their strengths as well as limitations are highlighted. There is a strong rationale for a vasopressor support in severe hemorrhagic shock. However, this should be tempered by the risk of excessive vasoconstriction during such hypovolemic state. The experimental models must be analyzed within their own limits and cannot be directly translated into clinical practice. In addition, because of many biases, the results of clinical trials are debatable. Therefore, based on current information, further clinical trials comparing early vasopressor support plus fluid resuscitation versus fluid resuscitation alone are warranted.
Lumpectomy Plus Tamoxifen With or Without Irradiation in Women Age 70 Years or Older With Early Breast Cancer: Long-Term Follow-Up of CALGB 9343
Authors: Hughes Kevin S. , Schnaper Lauren A. , Bellon Jennifer R. , Cirrincione Constance T. , Berry Donald A. , McCormick Beryl , Muss Hyman B. , Smith Barbara L. , Hudis Clifford A. , Winer Eric P. , Wood William C.
Published: May 2013

Purpose

To determine whether there is a benefit to adjuvant radiation therapy after breast-conserving surgery and tamoxifen in women age ≥ 70 years with early-stage breast cancer.

Patients and Methods

Between July 1994 and February 1999, 636 women (age ≥ 70 years) who had clinical stage I (T1N0M0 according to TNM classification) estrogen receptor (ER) –positive breast carcinoma treated by lumpectomy were randomly assigned to receive tamoxifen plus radiation therapy (TamRT; 317 women) or tamoxifen alone (Tam; 319 women). Primary end points were time to local or regional recurrence, frequency of mastectomy, breast cancer–specific survival, time to distant metastasis, and overall survival (OS).

Results

Median follow-up for treated patients is now 12.6 years. At 10 years, 98% of patients receiving TamRT (95% CI, 96% to 99%) compared with 90% of those receiving Tam (95% CI, 85% to 93%) were free from local and regional recurrences. There were no significant differences in time to mastectomy, time to distant metastasis, breast cancer–specific survival, or OS between the two groups. Ten-year OS was 67% (95% CI, 62% to 72%) and 66% (95% CI, 61% to 71%) in the TamRT and Tam groups, respectively.

Conclusion

With long-term follow-up, the previously observed small improvement in locoregional recurrence with the addition of radiation therapy remains. However, this does not translate into an advantage in OS, distant disease-free survival, or breast preservation. Depending on the value placed on local recurrence, Tam remains a reasonable option for women age ≥ 70 years with ER-positive early-stage breast cancer.
Effects of a Telephone-Delivered Multiple Health Behavior Change Intervention (CanChange) on Health and Behavioral Outcomes in Survivors of Colorectal Cancer: A Randomized Controlled Trial
Authors: Hawkes Anna L. , Chambers Suzanne K. , Pakenham Kenneth I. , Patrao Tania A. , Baade Peter D. , Lynch Brigid M. , Aitken Joanne F. , Meng Xingqiong , Courneya Kerry S.
Published: May 2013

Purpose

Colorectal cancer survivors are at risk for poor health outcomes because of unhealthy lifestyles, but few studies have developed translatable health behavior change interventions. This study aimed to determine the effects of a telephone-delivered multiple health behavior change intervention (CanChange) on health and behavioral outcomes among colorectal cancer survivors.

Methods

In this two-group randomized controlled trial, 410 colorectal cancer survivors were randomly assigned to the health coaching intervention (11 theory-based telephone-delivered health coaching sessions delivered over 6 months focusing on physical activity, weight management, dietary habits, alcohol, and smoking) or usual care. Assessment of primary (ie, physical activity [Godin Leisure Time Index], health-related quality of life [HRQoL; Short Form–36], and cancer-related fatigue [Functional Assessment of Chronic Illness Therapy Fatigue Scale]) and secondary outcomes (ie, body mass index [kg/m2], diet and alcohol intake [Food Frequency Questionnaire], and smoking) were conducted at baseline and 6 and 12 months.

Results

At 12 months, significant intervention effects were observed for moderate physical activity (28.5 minutes; P = .003), body mass index (−0.9 kg/m2; P = .001), energy from total fat (−7.0%; P = .006), and energy from saturated fat (−2.8%; P = .016). A significant intervention effect was reported for vegetable intake (0.4 servings per day; P = .001) at 6 months. No significant group differences were found at 6 or 12 months for HRQoL, cancer-related fatigue, fruit, fiber, or alcohol intake, or smoking.

Conclusion

The CanChange intervention was effective for improving physical activity, dietary habits, and body mass index in colorectal cancer survivors. The intervention is translatable through existing telephone cancer support and information services in Australia and other countries.
Prognostic Score Including Gene Mutations in Chronic Myelomonocytic Leukemia
Authors: Itzykson Raphaël , Kosmider Olivier , Renneville Aline , Gelsi-Boyer Véronique , Meggendorfer Manja , Morabito Margot , Berthon Céline , Adès Lionel , Fenaux Pierre , Beyne-Rauzy Odile , Vey Norbert , Braun Thorsten , Haferlach Torsten , Dreyfus François , Cross Nicholas C.P. , Preudhomme Claude , Bernard Olivier A. , Fontenay Michaela , Vainchenker William , Schnittger Susanne , Birnbaum Daniel , Droin Nathalie , Solary Eric
Published: May 2013

Purpose

Several prognostic scoring systems have been proposed for chronic myelomonocytic leukemia (CMML), a disease in which some gene mutations—including ASXL1—have been associated with poor prognosis in univariable analyses. We developed and validated a prognostic score for overall survival (OS) based on mutational status and standard clinical variables.

Patients and Methods

We genotyped ASXL1 and up to 18 other genes including epigenetic (TET2, EZH2, IDH1, IDH2, DNMT3A), splicing (SF3B1, SRSF2, ZRSF2, U2AF1), transcription (RUNX1, NPM1, TP53), and signaling (NRAS, KRAS, CBL, JAK2, FLT3) regulators in 312 patients with CMML. Genotypes and clinical variables were included in a multivariable Cox model of OS validated by bootstrapping. A scoring system was developed using regression coefficients from this model.

Results

ASXL1 mutations (P < .0001) and, to a lesser extent, SRSF2 (P = .03), CBL (P = .003), and IDH2 (P = .03) mutations predicted inferior OS in univariable analysis. The retained independent prognostic factors included ASXL1 mutations, age older than 65 years, WBC count greater than 15 ×109/L, platelet count less than 100 ×109/L, and anemia (hemoglobin < 10 g/dL in female patients, < 11g/dL in male patients). The resulting five-parameter prognostic score delineated three groups of patients with median OS not reached, 38.5 months, and 14.4 months, respectively (P < .0001), and was validated in an independent cohort of 165 patients (P < .0001).

Conclusion

A new prognostic score including ASXL1 status, age, hemoglobin, WBC, and platelet counts defines three groups of CMML patients with distinct outcomes. Based on concordance analysis, this score appears more discriminative than those based solely on clinical parameters.