bluuebunny/crossref_metadata_2025 huggingface dataset:
Pride in Parsimony
Authors: Williams Lisa A. , DeSteno David
Published: March 2010

Tracy, Shariff, and Cheng (2010) present a timely and eloquent review of the current research on the emotion pride in terms of a naturalist framework. The present commentary not only echoes arguments relating to pride’s adaptive function, but also highlights some points of theoretical clarification. Specifically, we question the necessity of the naturalist approach and the emphasis on two facets of pride.
Mediating Mechanisms and Emotions
Authors: Rutter Michael
Published: March 2010

Kagan successfully forces us to re-examine our assumptions and concepts regarding the broad field of “emotion.” His postulated four phases start with the brain state provoked by some stimulus. While that constitutes a reasonable starting point, the specificity of the brain qualities provoked by different types of stimuli remains uncertain. The recommendations on the way forward are the least satisfying aspects of this article. Integration would have been helped by some consideration of the role of animal models, of the ways in which genes operate, and of the multiple varieties of gene—environment interplay.
Review: New direct-acting antivirals in the development for hepatitis C virus infection
Authors: Pockros Paul J.
Published: March 2010

A large number of new therapies are in development for chronic hepatitis C including direct-acting antiviral drugs (DAA), which target specific hepatitis C virus enzymes. Two of these compounds have already advanced into phase 3 development in the USA and EU, and many more are in phase 2 trials and likely to advance. In this review, the results of recent studies on ribavirin analogues, nonstructural (NS) 3/4 serine protease inhibitors, NS5B polymerase inhibitors, cyclophilin inhibitors, silimarin components, and thiazolides have been updated. Each compound includes a brief summary of its proposed mechanism of action, results of early clinical trials, and more advanced trial data where available. These compounds are likely to be the first approved in the USA and EU and will initially be used in combination with the current standard of care. It is possible that future treatment paradigms with these agents will offer the potential of interferon-free regimens. It is most likely that patients for these new therapies will be selected carefully by identifying and treating first those who have excellent sustained virologic response rates with 24 weeks of pegylated interferon and ribavirin, the current standard of care. It is also likely that there will be a need to identify those patients who are not likely to have a sustained virologic response with the addition of a protease inhibitor to the current standard of care and delaying their therapy until combination viral suppression therapy becomes an option. The cost and side effects of the DAA will be important considerations for treating physicians. This review is current through 2009; however, data are rapidly changing.
Tackling health determinants in rural India: the KHOJ initiative
Authors: Mukhopadhyay Alok
Published: March 2010

There have been significant public health achievements in recent years; not only do people live longer and healthier lives, but there has also been a decline in communicable diseases, like tuberculosis, and water-borne diseases, especially in developing countries like India. Although lifestylerelated problems are emerging globally, developing countries carry heavier burdens of poor health conditions, which is an issue of serious concern, in particular among marginalized populations. Reaching out to these groups is a global challenge, and particularly in India, where one-third of the population (between 250 and 300 million people) live in remote, difficult and vulnerable areas lacking basic amenities. In order to address the ‘health for all’ challenge, this Commentary advocates for the public, private and non-profit sectors to work together to implement innovative community-based approaches that address the various social determinants of health. The case of the Voluntary Health Association of India (VHAI), a national NGO, is presented as an example of successful coordinated community and policy actions to improve health determinants in remote rural areas of India. (Global Health Promotion, 2010; 17(1): pp. 69—72)
Building capacity in workplace health promotion: the case of the Healthy Together e-learning project
Authors: Hodgins Margaret , Battel-Kirk Barbara , Asgeirsdottir Asa G.
Published: March 2010

The current global economic crisis poses major challenges for workplace health promotion (WHP). Activities that are not perceived to obviously and directly contribute to profits could be sacrificed. This paper argues that WHP must remain centre-stage because of the rights of workers to a healthy, safe working environment but also because of WHP’s beneficial financial implications for enterprises. Capacity building for WHP can be developed even within a recessionary environment, particularly if the focus is on the wider workforce, described here as people for whom workplace health promotion may not be their primary function but who have an important role to play in health improvement in workplaces. There is a strong case for the development of the wider workforce based both on the lack of suitably qualified specialists and on the practicalities of having WHP implemented within organizations, particularly for small and medium-sized enterprises (SMEs). SMEs make up a very significant proportion of the global economy and are identified as a priority area for action internationally. An example of an e-learning course, the Healthy Together programme, developed by a partnership of three countries, is discussed as an approach that has potential to develop capacity for WHP in the current climate. The findings of the evaluation of the Healthy Together programme indicate that there is a real potential in developing e-learning materials for training those with a brief for promoting workplace health and safety in SMEs. Although modifications in some aspects of delivery identified in the evaluation of the pilot course need to be considered, the course was well received, and was reported to be relevant to the learning needs of students, to their workplaces and specifically to small businesses in rural areas. Specific features of the e-learning approach increase its potential to address capacity building for WHP. (Global Health Promotion, 2010; 17(1): pp. 60—68)
The sirens’ song of empowerment: a case study of health promotion and the New Zealand Prostitutes Collective
Authors: Laverack Glenn , Whipple Amanda
Published: March 2010

The New Zealand Prostitutes Collective (NZPC) formed in 1987 with the intention of reforming the policy that governed prostitution. The Prostitution Reform Act 2003 was created to protect sex workers from exploitation and to give them the same rights as other workers by protecting their occupation health and safety. It is an example of community empowerment in which a small and relatively powerless group of women strived to achieve social justice and equity for all sex workers. This article provides, for the first time, the story of how the NZPC was not only able to decriminalize prostitution but also to form a framework that safeguarded the rights of all sex workers in New Zealand. It is a fascinating case study that provides insightful information into how one civil society group had a direct influence on public policy. The implications of the case study to health promotion practice are discussed and will be of interest to planners and practitioners involved in the strengthening of community empowerment. (Global Health Promotion, 2010; 17(1): pp. 33—38)
Prévention et réduction des inégalités de santé : une conciliation difficile
Authors: Aïach Pierre , Baumann Michèle
Published: March 2010

La baisse continue de la mortalité dans la plupart des pays européens pose la question difficile de la part à attribuer à la prévention dans ce phénomène. Une autre question est de plus en plus fréquemment posée : dans quelle mesure cette amélioration générale de l’état de santé contribue à la réduction des inégalités sociales de santé ? On peut retenir l’idée que les mesures préventives, en particulier celles liées aux comportements individuels, ne produisent pas les mêmes effets en fonction de la vulnérabilité différentielle des personnes. De plus, l’appropriation des bonnes conduites sanitaires et l’abandon des mauvaises est majoritairement fonction du capital culturel détenu. Cela résulte de l’effet lié à la disposition différentielle, socialement acquise, à l’appropriation des ressources et connaissances en matière de soins ou de conduites préventives. (Global Health Promotion, 2010; 17 (1): pp. 95—98)
Bone marrow graft-versus-host disease: early destruction of hematopoietic niche after MHC-mismatched hematopoietic stem cell transplantation
Authors: Shono Yusuke , Ueha Satoshi , Wang Yong , Abe Jun , Kurachi Makoto , Matsuno Yoshihiro , Sugiyama Tatsuki , Nagasawa Takashi , Imamura Masahiro , Matsushima Kouji
Published: March 2010

Disrupted hematopoiesis and delayed immune reconstitution are life-threatening complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although graft-versus-host disease (GVHD) is a major risk factor for the bone marrow (BM) insufficiency, how GVHD impairs BM hematopoiesis has been largely unknown. We hypothesized that BM stromal niche could be a target of GVHD. In major histocompatibility complex (MHC)–mismatched murine models of GVHD, we have demonstrated the early destruction of osteoblasts that especially affected B-cell lineages. The defective B lymphopoiesis was due to the impaired ability of BM stroma and osteoblasts to support the hematopoiesis, as evidenced by the failure of GVHD-affected BM to reconstitute the hematopoietic cells. The administration of anti-CD4 monoclonal antibody (mAb) ameliorated these effects and improved B lymphopoiesis while preserving graft-versus-tumor effects. Genetic ablation of Fas–Fas ligand signaling also partially restored B lymphopoiesis. Our present study provided evidence of BM GVHD, with the identification of osteoblasts as the main target for GVHD in BM. Moreover, our data showed the potential for mAb therapies to enhance immune reconstitution in vivo for patients undergoing allo-HSCT.
Homo-binding character of LMO2 isoforms and their both synergic and antagonistic functions in regulating hematopoietic-related target genes
Authors: Sun Wei , Shen Wen-Wen , Yang Shuang , Hu Fen , Gao Yang , Qiao Yu-Huan , Zhu Tian-Hui
Published: March 2010

Background

The human lmo2 gene plays important roles in hematopoiesis and is associated with acute T lymphocyte leukemia. The gene encodes two protein isoforms, a longer form LMO2-L and a shorter form LMO2-S. Both isoforms function as bridge molecules to assemble their partners together to regulate their target genes. A typical LMO2 binding site consists of two elements, a GATA site and an E-box, with an interval of 9~12 bp.

Methods

In this study, the combination of MBP pulldown assay and mammalian two hybrid assay were used to confirm the homo-binding character of LMO2-L/-S isoforms. Luciferase reporter assay and Real-time PCR assay were used to detect expression levels and relative promoter activities of LMO2-L/-S isoforms. Co-transfection and Luciferase reporter assay were used to reveal the detailed regulatory pattern of LMO2-L/-S isoforms on their targets.

Results

Herein we report the homo-interaction character of LMO2-L and LMO2-S and their major difference in manner of regulating their target genes. Our results showed that LMO2-L and LMO2-S could only bind to themselves but not each other. It was also demonstrated that LMO2-L could either positively or negatively regulate the transcription of its different target genes, depending on the arrangement and strand location of the two elements GATA site and E-box, LMO2-S, however, performed constitutively transcriptional inhibiting function on all target genes.

Conclusion

These results suggest that LMO2 isoforms have independent functions while there is no interaction between each other and they could play synergetic or antagonistic roles precisely in regulating their different genes involved in normal and aberrant hematopoiesis.
Knowledge-guided gene ranking by coordinative component analysis
Authors: Wang Chen , Xuan Jianhua , Li Huai , Wang Yue , Zhan Ming , Hoffman Eric P , Clarke Robert
Published: March 2010

Background

In cancer, gene networks and pathways often exhibit dynamic behavior, particularly during the process of carcinogenesis. Thus, it is important to prioritize those genes that are strongly associated with the functionality of a network. Traditional statistical methods are often inept to identify biologically relevant member genes, motivating researchers to incorporate biological knowledge into gene ranking methods. However, current integration strategies are often heuristic and fail to incorporate fully the true interplay between biological knowledge and gene expression data.

Results

To improve knowledge-guided gene ranking, we propose a novel method called coordinative component analysis (COCA) in this paper. COCA explicitly captures those genes within a specific biological context that are likely to be expressed in a coordinative manner. Formulated as an optimization problem to maximize the coordinative effort, COCA is designed to first extract the coordinative components based on a partial guidance from knowledge genes and then rank the genes according to their participation strengths. An embedded bootstrapping procedure is implemented to improve statistical robustness of the solutions. COCA was initially tested on simulation data and then on published gene expression microarray data to demonstrate its improved performance as compared to traditional statistical methods. Finally, the COCA approach has been applied to stem cell data to identify biologically relevant genes in signaling pathways. As a result, the COCA approach uncovers novel pathway members that may shed light into the pathway deregulation in cancers.

Conclusion

We have developed a new integrative strategy to combine biological knowledge and microarray data for gene ranking. The method utilizes knowledge genes for a guidance to first extract coordinative components, and then rank the genes according to their contribution related to a network or pathway. The experimental results show that such a knowledge-guided strategy can provide context-specific gene ranking with an improved performance in pathway member identification.
A clustered set of three Sp-family genes is ancestral in the Metazoa: evidence from sequence analysis, protein domain structure, developmental expression patterns and chromosomal location
Authors: Schaeper Nina D , Prpic Nikola-Michael , Wimmer Ernst A
Published: March 2010

Background

The Sp-family of transcription factors are evolutionarily conserved zinc finger proteins present in many animal species. The orthology of the Sp genes in different animals is unclear and their evolutionary history is therefore controversially discussed. This is especially the case for the Sp gene buttonhead (btd) which plays a key role in head development in Drosophila melanogaster, and has been proposed to have originated by a recent gene duplication. The purpose of the presented study was to trace orthologs of btd in other insects and reconstruct the evolutionary history of the Sp genes within the metazoa.

Results

We isolated Sp genes from representatives of a holometabolous insect (Tribolium castaneum), a hemimetabolous insect (Oncopeltus fasciatus), primitively wingless hexapods (Folsomia candida and Thermobia domestica), and an amphipod crustacean (Parhyale hawaienis). We supplemented this data set with data from fully sequenced animal genomes. We performed phylogenetic sequence analysis with the result that all Sp factors fall into three monophyletic clades. These clades are also supported by protein domain structure, gene expression, and chromosomal location. We show that clear orthologs of the D. melanogaster btd gene are present even in the basal insects, and that the Sp5-related genes in the genome sequence of several deuterostomes and the basal metazoans Trichoplax adhaerens and Nematostella vectensis are also orthologs of btd.

Conclusions

All available data provide strong evidence for an ancestral cluster of three Sp-family genes as well as synteny of this Sp cluster and the Hox cluster. The ancestral Sp gene cluster already contained a Sp5/btd ortholog, which strongly suggests that btd is not the result of a recent gene duplication, but directly traces back to an ancestral gene already present in the metazoan ancestor.
Estimation of divergence time between two sibling species of the Anopheles (Kerteszia) cruziicomplex using a multilocus approach
Authors: Rona Luísa DP , Carvalho-Pinto Carlos J , Mazzoni Camila J , Peixoto Alexandre A
Published: March 2010

Background

Anopheles cruziiis the primary humanPlasmodiumvector in southern and southeastern Brazil. The distribution of this mosquito follows the coast of the Brazilian Atlantic Forest. Previous studies indicated thatAn. cruziiis a complex of cryptic species.

Results

A multilocus approach using six loci, three circadian clock genes and three encoding ribosomal proteins, was implemented to investigate in more detail the genetic differentiation between theAn. cruziipopulations from Santa Catarina (southern Brazil) and Bahia States (northeastern Brazil) that represent two sibling species. The analysis revealed very highFSTvalues and fixed differences between the twoAn. cruziisibling species in all loci, irrespective of their function. An Isolation with Migration model was fit to the data using the IM program. The results reveal no migration in either direction and allowed a rough estimate of the divergence time between the two sibling species.

Conclusions

Population genetics analysis ofAn. cruziisamples from two Brazilian localities using a multilocus approach confirmed that they represent two different sibling species in this complex. The results suggest that the two species have not exchanged migrants since their separation and that they possibly diverged between 1.1 and 3.6 million years ago, a period of intense climatic changes.
Identification and characterization of the intracellular poly-3-hydroxybutyrate depolymerase enzyme PhaZ of Sinorhizobium meliloti
Authors: Trainer Maria A , Capstick David , Zachertowska Alicja , Lam Kathy N , Clark Scott RD , Charles Trevor C
Published: March 2010

Background

S. meliloti forms indeterminate nodules on the roots of its host plant alfalfa (Medicago sativa). Bacteroids of indeterminate nodules are terminally differentiated and, unlike their non-terminally differentiated counterparts in determinate nodules, do not accumulate large quantities of Poly-3-hydroxybutyrate (PHB) during symbiosis. PhaZ is in intracellular PHB depolymerase; it represents the first enzyme in the degradative arm of the PHB cycle in S. meliloti and is the only enzyme in this half of the PHB cycle that remains uncharacterized.

Results

The S. meliloti phaZ gene was identified by in silico analysis, the ORF was cloned, and a S. meliloti phaZ mutant was constructed. This mutant exhibited increased PHB accumulation during free-living growth, even when grown under non-PHB-inducing conditions. The phaZ mutant demonstrated no reduction in symbiotic capacity; interestingly, analysis of the bacteroids showed that this mutant also accumulated PHB during symbiosis. This mutant also exhibited a decreased capacity to tolerate long-term carbon starvation, comparable to that of other PHB cycle mutants. In contrast to other PHB cycle mutants, the S. meliloti phaZ mutant did not exhibit any decrease in rhizosphere competitiveness; however, this mutant did exhibit a significant increase in succinoglycan biosynthesis.

Conclusions

S. meliloti bacteroids retain the capacity to synthesize PHB during symbiosis; interestingly, accumulation does not occur at the expense of symbiotic performance. phaZ mutants are not compromised in their capacity to compete for nodulation in the rhizosphere, perhaps due to increased succinoglycan production resulting from upregulation of the succinoglycan biosynthetic pathway. The reduced survival capacity of free-living cells unable to access their accumulated stores of PHB suggests that PHB is a crucial metabolite under adverse conditions.
Defining reference genes in Oryza sativausing organ, development, biotic and abiotic transcriptome datasets
Authors: Narsai Reena , Ivanova Aneta , Ng Sophia , Whelan James
Published: March 2010

Background

Reference genes are widely used to normalise transcript abundance data determined by quantitative RT-PCR and microarrays. However, the approaches taken to define reference genes can be variable. Although Oryza sativa (rice) is a widely used model plant and important crop specie, there has been no comprehensive analysis carried out to define superior reference genes.

Results

Analysis of 136 Affymetrix transcriptome datasets comprising of 373 genome microarrays from studies in rice that encompass tissue, developmental, abiotic, biotic and hormonal transcriptome datasets identified 151 genes whose expression was considered relatively stable under all conditions. A sub-set of 12 of these genes were validated by quantitative RT-PCR and were seen to be stable under a number of conditions. All except one gene that has been previously proposed as a stably expressed gene for rice, were observed to change significantly under some treatment.

Conclusion

A new set of reference genes that are stable across tissue, development, stress and hormonal treatments have been identified in rice. This provides a superior set of reference genes for future studies in rice. It confirms the approach of mining large scale datasets as a robust method to define reference genes, but cautions against using gene orthology or counterparts of reference genes in other plant species as a means of defining reference genes.
Cancer resistance of SR/CR mice in the genetic knockout backgrounds of leukocyte effector mechanisms: determinations for functional requirements
Authors: Sanders Anne M , Stehle John R , Blanks Michael J , Riedlinger Gregory , Kim-Shapiro Jung W , Monjazeb Arta M , Adams Jonathan M , Willingham Mark C , Cui Zheng
Published: March 2010

Background

Spontaneous Regression/Complete Resistant (SR/CR) mice are a colony of cancer-resistant mice that can detect and rapidly destroy malignant cells with innate cellular immunity, predominately mediated by granulocytes. Our previous studies suggest that several effector mechanisms, such as perforin, granzymes, or complements, may be involved in the killing of cancer cells. However, none of these effector mechanisms is known as critical for granulocytes. Additionally, it is unclear which effector mechanisms are required for the cancer killing activity of specific leukocyte populations and the survival of SR/CR mice against the challenges of lethal cancer cells. We hypothesized that if any of these effector mechanisms was required for the resistance to cancer cells, its functional knockout in SR/CR mice should render them sensitive to cancer challenges. This was tested by cross breeding SR/CR mice into the individual genetic knockout backgrounds of perforin (Prf-/-), superoxide (Cybb-/), or inducible nitric oxide (Nos2-/).

Methods

SR/CR mice were bred into individual Prf-/-, Cybb-/-, or Nos2-/- genetic backgrounds and then challenged with sarcoma 180 (S180). Their overall survival was compared to controls. The cancer killing efficiency of purified populations of macrophages and neutrophils from these immunodeficient mice was also examined.

Results

When these genetically engineered mice were challenged with cancer cells, the knockout backgrounds of Prf-/-, Cybb-/-, or Nos2-/- did not completely abolish the SR/CR cancer resistant phenotype. However, the Nos2-/- background did appear to weaken the resistance. Incidentally, it was also observed that the male mice in these immunocompromised backgrounds tended to be less cancer-resistant than SR/CR controls.

Conclusion

Despite the previously known roles of perforin, superoxide or nitric oxide in the effector mechanisms of innate immune responses, these effector mechanisms were not required for cancer-resistance in SR/CR mice. The resistance was functional when any one of these effector mechanisms was completely absent, except some noticeably reduced penetrance, but not abolishment, of the phenotype in the male background in comparison to female background. These results also indicate that some other effector mechanism(s) of granulocytes may be involved in the killing of cancer cells in SR/CR mice.
Differing effect of systemic anti psoriasis therapies on platelet physiology - a case report and review of literature
Authors: Davidovici Batya B , Sullivan-Whalen Mary M , Gilleaudeau Patricia , Krueger James G
Published: March 2010

Background

Psoriasis is a common, chronic relapsing inflammatory skin disease. Lately, there is increasing evidence that psoriasis is more than "skin deep". Epidemiological studies showed that severe psoriasis might have also important systemic manifestations such as metabolic deregulations, cardiovascular disease (CVD) and increased mortality. Moreover, recently psoriasis patients were found to have platelet hyperactivity.

Case Presentation

This is a case report and review of the literature. We present a patient with long standing severe psoriasis vulgaris with marked thrombocytosis. His thrombocytosis did not correlate with disease severity but rather with the different treatments that he was exposed to, subsiding only during treatment with anti Tumor Necrosis Factor (TNF)- agents. A literature review revealed that in rheumatoid arthritis, another systemic inflammatory disease; interleukin (IL)-6 might be implicated in causing thrombocytosis.

Conclusion

This unique case report illustrates that different systemic treatments for psoriasis might have implications beyond the care of skin lesions. This insight is especially important in psoriasis patients in view of their deranged hemostatic balance toward a prothrombotic state, which might increase the risk of thrombosis and CVD. Therefore, further studies analyzing the effect of different drugs on platelets physiology are warranted.
Protective effects of Spirulina maxima on hyperlipidemia and oxidative-stress induced by lead acetate in the liver and kidney
Authors: Ponce-Canchihuamán Johny C , Pérez-Méndez Oscar , Hernández-Muñoz Rolando , Torres-Durán Patricia V , Juárez-Oropeza Marco A
Published: March 2010

Background

Oxidative damage has been proposed as a possible mechanism involved in lead toxicity, specially affecting the liver and kidney. Previous studies have shown the antioxidant effect of Spirulina maxima in several experimental models of oxidative stress. The current study was carried out to evaluate the antioxidant activity of Spirulina maxima against lead acetate-induced hyperlipidemia and oxidative damage in the liver and kidney of male rats. Control animals were fed on a standard diet and did not receive lead acetate (Control group). Experimental animals were fed on a standard laboratory diet with or without Spirulina maxima 5% in the standard laboratory diet and treated with three doses of lead acetate (25 mg each/weekly, intraperitoneal injection) (lead acetate with Spirulina, and lead acetate without Spirulina groups).

Results

The results showed that Spirulina maxima prevented the lead acetate-induced significant changes on plasma and liver lipid levels and on the antioxidant status of the liver and kidney. On the other hand, Spirulina maxima succeeded to improve the biochemical parameters of the liver and kidney towards the normal values of the Control group.

Conclusions

It was concluded that Spirulina maxima has protective effects on lead acetate-induced damage, and that the effects are associated with the antioxidant effect of Spirulina.
Impact of neoadjuvant treatment on total mesorectal excision for ultra-low rectal cancers
Authors: Lim Yon Kuei , Law Wai Lun , Liu Rico , Poon Jensen TC , Fan Joe FM , Lo Oswens SH
Published: March 2010

Background

This study reviewed the impact of pre-operative chemoradiotherapy or post-operative chemotherapy and/or radiotherapy on total mesorectal excision (TME) for ultralow rectal cancers that required either low anterior resection with peranal coloanal anastomosis or abdomino-perineal resection (APR). We examined surgical complications, local recurrence and survival.

Methods

Of the 1270 patients who underwent radical resection for rectal cancer from 1994 till 2007, 180 with tumors within 4 cm with either peranal coloanal anastomosis or APR were analyzed. Patients were compared in groups that had surgery only (Group A), pre-operative chemoradiotherapy (Group B), and post-operative therapy (Group C).

Results

There were 115 males and the mean age was 65.43 years (range 30-89). APR was performed in 134 patients while 46 had a sphincter-preserving resection with peranal coloanal anastomosis. The mean follow-up period was 52.98 months (range: 0.57 to 178.9). There were 69, 58 and 53 patients in Groups A, B, and C, respectively. Nine patients in Group B could go on to have sphincter-saving rectal resection. The overall peri-operative complication rate was 43.4% in Group A vs. 29.3% in Group B vs. 39.6% in Group C, respectively. The local recurrence rate was significantly lower in Group B (8.6.9% vs. 21.7% in Group A vs. 33.9% in Group C) p < 0.05. The 5-year cancer-specific survival rates for Group A was 49.3%, Group B was 69.9% and Group C was 38.8% (p = 0.14).

Conclusion

Pre-operative chemoradiation in low rectal cancer is not associated with a higher incidence of peri-operative complications and its benefits may include reduction local recurrence.
OST-HTH: a novel predicted RNA-binding domain
Authors: Anantharaman Vivek , Zhang Dapeng , Aravind L
Published: March 2010

Background

The mechanism by which the arthropod Oskar and vertebrate TDRD5/TDRD7 proteins nucleate or organize structurally related ribonucleoprotein (RNP) complexes, the polar granule and nuage, is poorly understood. Using sequence profile searches we identify a novel domain in these proteins that is widely conserved across eukaryotes and bacteria.

Results

Using contextual information from domain architectures, sequence-structure superpositions and available functional information we predict that this domain is likely to adopt the winged helix-turn-helix fold and bind RNA with a potential specificity for dsRNA. We show that in eukaryotes this domain is often combined in the same polypeptide with protein-protein- or lipid- interaction domains that might play a role in anchoring these proteins to specific cytoskeletal structures.

Conclusions

Thus, proteins with this domain might have a key role in the recognition and localization of dsRNA, including miRNAs, rasiRNAs and piRNAs hybridized to their targets. In other cases, this domain is fused to ubiquitin-binding, E3 ligase and ubiquitin-like domains indicating a previously under-appreciated role for ubiquitination in regulating the assembly and stability of nuage-like RNP complexes. Both bacteria and eukaryotes encode a conserved family of proteins that combines this predicted RNA-binding domain with a previously uncharacterized domain (DUF88). We present evidence that it is an RNAse belonging to the superfamily that includes the 5'->3' nucleases, PIN and NYN domains and might be recruited to degrade certain RNAs.

Reviewers

This article was reviewed by Sandor Pongor and Arcady Mushegian.
EBV-associated post-transplantation B-cell lymphoproliferative disorder following allogenic stem cell transplantation for acute lymphoblastic leukaemia: tumor regression after reduction of immunosuppression - a case report
Authors: Krenauer Alexander , Moll Alexander , Pönisch Wolfram , Schmitz Nicole , Niedobitek Gerald , Niederwieser Dietger , Aigner Thomas
Published: March 2010

Epstein-Barr virus (EBV)-associated B-cell post-transplantation lymphoproliferative disorder (PTLD) is a severe complication following stem cell transplantation. This is believed to occur as a result of iatrogenic immunosuppression leading to a relaxation of T-cell control of EBV infection and thus allowing viral reactivation and proliferation of EBV-infected B-lymphocytes. In support of this notion, reduction of immunosuppressive therapy may lead to regression of PTLD.

We present a case of an 18-year-old male developing a monomorphic B-cell PTLD 2 months after receiving an allogenic stem cell transplant for acute lymphoblastic leukemia. Reduction of immunosuppressive therapy led to regression of lymphadenopathy. Nevertheless, the patient died 3 months afterwards due to extensive graft-vs.-host-disease and sepsis. As a diagnostic lymph node biopsy was performed only after reduction of immunosuppressive therapy, we are able to study the histopathological changes characterizing PTLD regression. We observed extensive apoptosis of blast cells, accompanied by an abundant infiltrate comprising predominantly CD8-positive, Granzyme B-positive T-cells. This observation supports the idea that regression of PTLD is mediated by cytotoxic T-cells and is in keeping with the observation that T-cell depletion, represents a major risk factor for the development of PTLD.
Bayesian multi-QTL mapping for growth curve parameters
Authors: Heuven Henri C M , Janss Luc L G
Published: March 2010

Background

Identification of QTL affecting a phenotype which is measured multiple times on the same experimental unit is not a trivial task because the repeated measures are not independent and in most cases show a trend in time. A complicating factor is that in most cases the mean increases non-linear with time as well as the variance. A two- step approach was used to analyze a simulated data set containing 1000 individuals with 5 measurements each. First the measurements were summarized in latent variables and subsequently a genome wide analysis was performed of these latent variables to identify segregating QTL using a Bayesian algorithm.

Results

For each individual a logistic growth curve was fitted and three latent variables: asymptote (ASYM), inflection point (XMID) and scaling factor (SCAL) were estimated per individual. Applying an 'animal' model showed heritabilities of approximately 48% for ASYM and SCAL while the heritability for XMID was approximately 24%. The genome wide scan revealed four QTLs affecting ASYM, one QTL affecting XMID and four QTLs affecting SCAL. The size of the QTL differed. QTL with a larger effect could be more precisely located compared to QTL with small effect. The locations of the QTLs for separate parameters were very close in some cases and probably caused the genetic correlation observed between ASYM and XMID and SCAL respectively. None of the QTL appeared on chromosome five.

Conclusions

Repeated observations on individuals were affected by at least nine QTLs. For most QTL a precise location could be determined. The QTL for the inflection point (XMID) was difficult to pinpoint and might actually exist of two closely linked QTL on chromosome one.
Matrix-metalloproteinase-2, -8 and -9 in serum and skin blister fluid in patients with severe sepsis
Authors: Gäddnäs Fiia P , Sutinen Meeri M , Koskela Marjo , Tervahartiala Taina , Sorsa Timo , Salo Tuula A , Laurila Jouko J , Koivukangas Vesa , Ala-Kokko Tero I , Oikarinen Aarne
Published: March 2010

Introduction

Matrix metalloproteinases (MMPs) have various roles in inflammatory states. They seem to be able to modulate endothelial barriers and regulate the activity of chemokines and cytokines. The timely development of the levels during severe sepsis and thereafter have not been investigated. In addition it was of interest to study alterations of MMP-levels in intact skin, as the skin is the largest barrier against external pathogens and MMPs have not been studied at organ level in human sepsis. The aim of this study was to investigate the timely development of serum and skin MMP-2, -8 and -9 levels in human severe sepsis and their association with disease severity and mortality.

Methods

Forty-four patients with severe sepsis and fifteen healthy controls were included in this prospective longitudinal study. The amounts of MMP-2, -8 and -9 were analyzed from serum at days 1, 4, 6, 8, and 10, and from skin suction blister fluid at days 1 and 5 from the beginning of severe sepsis. Additionally, samples from the survivors were obtained after three and six months.

Results

The levels of MMP-2 and -8 were up-regulated in severe sepsis in comparison to healthy controls in skin blister fluid and serum. Compared to the controls MMP-9 levels were lower in sepsis from the fourth day on in serum and both the first and fifth day in skin blister fluid. Active forms of MMP-2 and -9 were present only in severe sepsis. The non-survivors had higher pro- and active MMP-2 levels than the survivors in skin blister fluid samples. Furthermore, MMP-2 levels were more pronounced in blister fluid and serum samples in patients with more severe organ failures. In the survivors at 3 and 6 month follow-up the MMP levels had returned to normal.

Conclusions

MMP-2 and -8 are elevated in serum and blister fluid in severe sepsis, implying that they may play a significant role in the pathogenesis of severe sepsis and organ dysfunctions. Active forms of MMP-2 and 9 were only present in patients with severe sepsis, and higher MMP-2 levels in skin blister and serum were associated with more severe organ dysfunctions.
Systemic levels of G-CSF and interleukin-6 determine the angiogenic potential of bone marrow resident monocytes
Authors: Gregory Alyssa D , Capoccia Benjamin J , Woloszynek Jill R , Link Daniel C
Published: March 2010

Systemic signals generated by ischemia lead to STAT3 activation and M2 polarization in bone marrow-resident monocytes.

There is considerable interest in the potential of cell-based approaches to mediate therapeutic angiogenesis for acute and chronic vascular syndromes. Using a mouse model of HLI, we showed previously that adoptive transfer of a small number of donor monocytes enhanced revascularization significantly. Herein, we provide data suggesting that the BM resident monocytes sense systemic signals that influence their future functional capacity. Specifically, following induction of distant ischemia, the angiogenic capacity of BM resident monocytes is reduced markedly. We provide evidence that G-CSF and IL-6 represent such “conditioning” signals. Systemic levels of G-CSF and IL-6 are increased significantly following induction of HLI. Accordingly, BM resident monocytes from ischemic mice exhibited increased pSTAT3 and STAT3 target gene expression. Finally, G-CSFR−/− and IL-6−/− mice were resistant to the deleterious effects of ischemic conditioning on monocyte angiogenic potential. RNA expression profiling suggested that ischemia-conditioned monocytes in the BM up-regulate the well-described M2 polarization markers Chi3l4 and Lrg1. Consistent with this observation, M2-skewed monocytes from SHIP−/− mice also had impaired angiogenic capacity. Collectively, these data show that G-CSF and IL-6 provide signals that determine the angiogenic potential of BM resident monocytes.
Editorial: Monocyte subpopulations and lentiviral infection
Authors: Crowe Suzanne M , Ziegler-Heitbrock Loems
Published: March 2010

Role of CD14+CD16+ monocyte subsets are discussed within HIV-1 infection and in relation to the findings of Kim et al. in this issue.
Efficacy and acceptability of mood stabilisers in the treatment of acute bipolar depression: systematic review
Authors: Van Lieshout Ryan J. , MacQueen Glenda M.
Published: March 2010

Background

Although people with bipolar disorder spend more time in a depressed than manic state, little evidence is available to guide the treatment of acute bipolar depression.

Aims

To compare the efficacy, acceptability and safety of mood stabiliser monotherapy with combination and antidepressant treatment in adults with acute bipolar depression.

Method

Systematic review and meta-analysis of randomised, double-blind controlled trials.

Results

Eighteen studies with a total 4105 participants were analysed. Mood stabiliser monotherapy was associated with increased rates of response (relative risk (RR) = 1.30, 95% CI 1.16–1.44, number needed to treat (NNT) = 10, 95% CI 7–18) and remission (RR = 1.51, 95% CI 1.27–1.79, NNT = 8, 95% CI 5–14) relative to placebo. Combination therapy was not statistically superior to monotherapy. Weight gain, switching and suicide rates did not differ between groups. No differences were found between individual medications or drug classes for any outcome.

Conclusions

Mood stabilisers are moderately efficacious for acute bipolar depression. Extant studies are few and limited by high rates of discontinuation and short duration. Further study of existing and novel agents is required.
Social communication deficits in disruptive primary-school
children
Authors: Donno R. , Parker G. , Gilmour J. , Skuse D. H.
Published: March 2010

Background

Parent and teacher data, from questionnaire surveys, suggest that
school-identified disruptive children often have pragmatic language
deficits of an autistic type.

Aims

This replication study aimed to confirm earlier findings, using
individual clinical assessment to investigate traits of autism-spectrum
disorder in disruptive children.

Method

Persistently disruptive children (n = 26) and a
comparison group (n = 22) were recruited from primary
schools in a deprived inner-city area. Measures included standardised
autism diagnostic interviews (with parents) and tests of IQ, social
cognition, theory of mind and attention (with children).

Results

The disruptive children possessed poorer pragmatic language skills
(P<0.0001) and mentalising abilities
(P<0.05) than comparisons. Nine disruptive
children (35%) met ICD–10 criteria for atypical autism or Asperger
syndrome.

Conclusions

Many persistently disruptive children have undetected disorders of social
communication, which are of potential aetiological significance.
Should our major classifications of mental disorders be
revised?
Authors: Goldberg David
Published: March 2010

Our major classification systems (DSM and ICD) face three main problems:
the high rates of ‘comorbidity’ that are produced by our present
diagnostic rules, the increasing use of ‘not elsewhere classified’ (NEC)
by practising clinicians, and the fact that each new edition is longer
and more complex than the one preceding it. A major simplification of the
chapter structure used by each classification might pave the way to
address these problems.
Early intervention in panic: pragmatic randomised controlled
trial
Authors: Meulenbeek Peter , Willemse Godelief , Smit Filip , van Balkom Anton , Spinhoven Philip , Cuijpers Pim
Published: March 2010

Background

Many people suffer from subthreshold and mild panic disorder and are at
risk of developing more severe panic disorder.

Aims

This study (trial registration: ISRCTN33407455) was conducted to evaluate
the effectiveness of an early group intervention based on
cognitive–behavioural principles to reduce panic disorder
symptomatology.

Method

Participants with subthreshold or mild panic disorder were recruited from
the general population and randomised to the intervention
(n = 109) or a waiting-list control group
(n = 108). The course was offered by 17 community
mental health centres.

Results

In the early intervention group, 43/109 (39%) participants presented with
a clinically significant change on the Panic Disorder Severity Scale–Self
Report (PDSS–SR) v. 17/108 (16%) in the control group
(odds ratio (OR) for favourable treatment response 3.49, 95% CI
1.77–6.88, P = 0.001). The course also had a positive
effect on DSM–IV panic disorder status (OR = 1.96, 95% CI=1.05–3.66,
P = 0.037). The PDSS–SR symptom reduction was also
substantial (between-group standardised mean difference of 0.68). The
effects were maintained at 6-month follow-up.

Conclusions

People presenting with subthreshold and mild panic disorder benefit from
this brief intervention.
Antidepressant use in adults with intellectual disability
Authors: Rai Prem R. , Kerr Mike
Published: March 2010

Aims and method

To study the use of antidepressants in adults with intellectual disability, focusing on medication type, indication, retention and clinical outcome. Case notes of all service users in a learning disability service were hand-searched to identify antidepressant usage, and those who had been treated with antidepressants and in whom at least 1 year of follow-up was possible were included in the study.

Results

A total of 241 treatment episodes were identified. The rates of positive outcome in terms of clinical improvement at 6 weeks, 6 months and 12 months were 49.4%, 48.1% and 49% respectively, and only 29 (12%) episodes of side-effects had been noted.

Clinical implications

Antidepressants are commonly prescribed in adults with intellectual disability. Approximately half did well in terms of clinical improvement.
Antipsychotic prescribing practice among child psychiatrists and community paediatricians
Authors: Otasowie John , Duffy Rachel , Freeman Jenny , Hollis Chris
Published: March 2010

Aims and method

All child and adolescent psychiatrists and community paediatricians in the former Trent Region were surveyed about their antipsychotic prescribing practice during 1 year, including monitoring, and whether they would like consensus guidelines on prescribing and monitoring of antipsychotics in children and adolescents.

Results

The majority (88%) of child psychiatrists and 33% of paediatricians had prescribed atypical antipsychotics, most commonly risperidone. Only two psychiatrists had prescribed a typical antipsychotic and no paediatrician had done so. Challenging behaviour in developmental disorders was the most common indication for atypicals. Both child psychiatrists and paediatricians prescribed atypicals for non-psychotic developmental disorders, whereas prescribing for psychosis occurred almost exclusively among psychiatrists. Height, weight and blood pressure were routinely monitored, but waist circumference was rarely measured and there was wide variation in the monitoring of other parameters such as blood glucose, prolactin and extrapyramidal side-effects. Three-quarters of the participants felt there was a need for guidance on prescribing and monitoring atypical antipsychotic therapy.

Clinical implications

The greater prescription of antipsychotics by child and adolescent psychiatrists may reflect differences in case-load and training. Routine monitoring of adverse effects is inconsistent among prescribers. The survey highlights the need for training and guidance on prescribing and monitoring of atypical antipsychotic use in children and adolescents.
Postcode lottery? Hospital transfers from one London prison and responsible catchment area
Authors: Wilson Simon , Chiu Katrina , Parrott Janet , Forrester Andrew
Published: March 2010

Aims and method

To consider the link between responsible commissioner and delayed prison transfers. All hospital transfers from one London prison in 2006 were audited and reviewed by the prisoner's borough of origin.

Results

Overall, 80 prisoners were transferred from the audited prison to a National Health Service (NHS) facility in 2006: 26% had to wait for more than 1 month for assessment by the receiving hospital unit and 24% had to wait longer than 3 months to be transferred. These 80 individuals were the responsibility of 16 different primary care trusts. Of the delayed transfer cases (n=19), the services commissioned by three primary care trusts were responsible for the delays.

Clinical implications

There are significant differences in performance between different primary care trusts related to hospital transfers of prisoners, with most hospitals able to admit urgent cases within 3 months. This suggests that a postcode lottery operates for prisoners requiring hospital transfer. Data from prison services may be useful in monitoring and improving the performance of local NHS services.