The Office International des Epizooties ad hoc Group on Non Tsetse Animal Trypanosomoses: Its Origin, Scope and Perspectives

A summary of the goals and activities of the ad hoc group on Non Tsetse Transmitted Animal Trypanosomosis belonging to the Office International des Epizooties is presented.

Contribution to the sand fly fauna (Diptera: Phlebotominae) of Rio Grande do Sul, Brazil and Leishmania (Viannia) infections

American cutaneous leishmaniasis (ACL) is endemic in the State of Rio Grande do Sul, Brazil. As reports of nearby hospitals suggest, the Parque Estadual do Turvo seems to serve as a source for the disease. During three months from November 1996 to February 1997 we collected, in this park, 2,228 sandflies (10 Lutzomyia species and 2 6species). We applied the polymerase chain reaction to 920 females which belong to the following species: Lutzomyia migonei, Lu. pessoai, Lu. fischeri, Lu. misionensis, Lu. lanei, Lu. neivai, Lu. shannoni, and Lu. monticola, in an attempt to verify natural infection by Leishmania (Viannia), the causative agent of ACL. Le. (Viannia) infections were demonstrated by DNA amplification from two Lu. pessoai and one Lu. misionensis female. Lu. pessoai have been found with leptomonas in the gut believed to be Le. (V.) braziliensis in other endemic areas of northeastern and southeastern Brazil. However, Lu. misionensis has never been found carrying a natural infection of Le. (Viannia).

Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research.

PURPOSE: This randomized phase II trial evaluated two docetaxel-based regimens to see which would be most promising according to overall response rate (ORR) for comparison in a phase III trial with epirubicin-cisplatin-fluorouracil (ECF) as first-line advanced gastric cancer therapy. PATIENTS AND METHODS: Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric carcinoma, a performance status <or= 1, and adequate hematologic, hepatic, and renal function randomly received <or= eight 3-weekly cycles of ECF (epirubicin 50 mg/m(2) on day 1, cisplatin 60 mg/m(2) on day 1, and fluorouracil [FU] 200 mg/m(2)/d on days 1 to 21), TC (docetaxel initially 85 mg/m(2) on day 1 [later reduced to 75 mg/m(2) as a result of toxicity] and cisplatin 75 mg/m(2) on day 1), or TCF (TC plus FU 300 mg/m(2)/d on days 1 to 14). Study objectives included response (primary), survival, toxicity, and quality of life (QOL). RESULTS: ORR was 25.0% (95% CI, 13% to 41%) for ECF, 18.5% (95% CI, 9% to 34%) for TC, and 36.6% (95% CI, 23% to 53%) for TCF (n = 119). Median overall survival times were 8.3, 11.0, and 10.4 months for ECF, TC, and TCF, respectively. Toxicity was acceptable, with one toxic death (TC arm). Grade 3 or 4 neutropenia occurred in more treatment cycles with docetaxel (TC, 49%; TCF, 57%; ECF, 34%). Global health status/QOL substantially improved with ECF and remained similar to baseline with both docetaxel regimens. CONCLUSION: Time to response and ORR favor TCF over TC for further evaluation, particularly in the neoadjuvant setting. A trend towards increased myelosuppression and infectious complications with TCF versus TC or ECF was observed.

Contribution of NFI-C to TGF-β1 signalling and tissue regeneration

Summary : Platelet Derived Growth Factor (PDGF) and Transforming Growth Factor-ß (TGF-ß) are two crucial growth factors in tissue repair and regeneration. They control migration and proliferation of macrophages and fibroblasts, as well as myofibroblast differentiation and synthesis of the new connective tissue. The transcription factor Nuclear Factor I-C (NFI-C) has been implicated in the TGF-ß pathway and regulation of extracellular matrix proteins in vitro. This suggests a possible implication of NFI-C in tissue repair. In this study, our purpose was to identify the NFI-C target genes in TGF-ß1 pathway activation and define the relationship between these two factors in cutaneous wound healing process. High-throughput genomic analysis in wild-type and NFI-C knock-out embryonic fibroblasts indicated that NFI-C acts as a repressor of the expression of genes which transcriptional activity is enhanced by TGF-ß. Interestingly, we found an over representation of genes involved in connective tissue inflammation and repair. In accordance with the genomic analysis, NFI-C-/- mice showed an improvement of skin healing during the inflammatory stage. Analysis of this new phenotype indicated that the expression of PDGFA and PDGF-Ra genes were increased in the wounds of NFI-C-/- mice resulting in early recruitment of macrophages and fibroblasts in the granulation tissue. In correlation with the stimulation effect of TGF-ß on myofibroblast differentiation we found an increased differentiation of these cells in null mice, providing a rationale for rapid wound closure. Thus, in the absence of NFI-C, both TGF-ß and PDGF pathways may be activated, leading to enhanced healing process. Therefore, the inhibition of NFI-C expression could constitute a suitable therapy for healing improvement. In addition, we identified a delay of hair follicle cycle initiation in NFI-C-/- mice. This prompted us to investigate the role of NFI-C in skin appendage. The transition from a quiescent to a proliferative phase requires a perfect timing of signalling modulation, leading to stem cell activation. As a consequence of cycle initiation delay in null mice, the activation of signalling involved in cell proliferation was also retarded. Interestingly, at the crucial moment of cell fate determination, we identified a decrease of CD34 gene in mutant mice. Since CD34 protein is involved in migration of multipotent cells, we suggest that NFI-C may be involved in stem cell mobilisation required for hair follicle renewal. Further investigations of the role of NFI-C in progenitor cell activation will lead to a better understanding of tissue regeneration and raise the possibility of treating alopecia with NFI-C-targeting treatment. In summary, this study demonstrates new regenerative functions of NFI-C in adult mice, which regulates skin repair and hair follicle renewal. Résumé : PDGF et TGF-ß sont des facteurs important du mécanisme de défense immunitaire. Ils influencent la prolifération et migration des macrophages et des fibroblastes, ainsi que la différenciation des myofibroblastes et la formation du nouveau tissu conjonctif. Le facteur de transcription NFI-C a été impliqué dans la voie de signalisation de TGF-ß et dans 1a régulation de l'expression des protéines de la matrice extracellulaire in vitro. Ces études antérieures laissent supposer que NFI-C serait un facteur important du remodelage tissulaire. Cependant le rôle de NFI-C dans un tissu comme la peau n'a pas encore été étudié. Dans ce travail, le but a été de d'identifier la relation qu'il existe entre I~1FI-C et TGF-ßl à un niveau transcriptionnel et dans le processus de cicatrisation cutanée in vivo. Ainsi, une analyse génétique à grande échelle, a permis d'indiquer que NFI-C agit comme un répresseur sur l'expression des gènes dont l'activité transcriptionnelle est activée par TGF-ß. De plus nous avons identifié un groupe de gènes qui controlent le développement et l'inflammation du tissue conjonctif. En relation avec ce résultat, l'absence de NFI-C dans la peau induit une cicatrisation plus rapide pendant la phase inflammatoire. Durant cette période, nous avons montré que les expressions de PDGFA et PDGFRa seraient plus élevées en absence de NFI-C. En conséquence, l'activation de la voie de PDGF induit une infiltration plus importante des macrophages et fibroblastes dans le tissue granuleux des souris mutantes. De plus, en corrélation avec le rôle de TGF-ßl dans la différenciation des myofibroblasts, nous avons observé une différenciation plus importante de ces cellules chez les animaux knock-out, ce qui peut expliquer une contraction plus rapide de la plaie. De plus, nous avons découvert que NFI-C est impliqué dans l'initiation du cycle folliculaire. La caractérisation de ce nouveau phénotype a montré un ralentissement de la transition telogène-anagène des souris NFI-C-/-. Or, un événement clé de cette transition est la modulation de plusieurs signaux moléculaires aboutissant à' l'activation des cellules souches. En corrélation avec le decalage du cycle, l'activation de ces signaux est également décalée dans les souris NFI-C-/-. Ainsi, au commencement de l'anagène, la prolifération des keratinocytes,NFI-C-/- est retardée et corrèle avec une diminution de l'expression de CD34, une protéine responsable de la détermination du migration des cellules multipotentes. Ainsi, NFI-C semble être impliqué dans la mobilisation des cellules souches qui sont nécessaires au renouvellement folliculaire. En résumé, NFI-C est impliqué dans la régulation des signaux moléculaires nécessaires à la réparation tissulaire et son inhibition pourrait constituer un traitement de la cicatrisation. L'analyse de son rôle dans l'activation des cellules souches permettrait de mieux comprendre le renouvellement tissulaire et, à long terme, d'améliorer les techniques de greffe des cellules souches épithéliales ou consituter une cible pour le traitement de l'alopecie.

IPH response to the Government Alcohol Advisory Group

The Institute of Public Health in Ireland (IPH) welcomes the call for submissions by the Government Alcohol Advisory Group and commends the Justice Minister, Brian Lenihan TD., for establishing this group. IPH aims to improve health on the island of Ireland, by working to combat health inequalities and influence public policies in favour of health.  IPH promotes cooperation between Northern Ireland and the Republic of Ireland in research, training, information and policy.   A report from IPH, Inequalities in Mortality 1989-1998 – A report on all-Ireland mortality data found that those in the lowest occupational class are 280% more likely to die from alcohol abuse than those in the highest occupational class. The poorer you are the more likely your life will be negatively impacted by alcohol.  In addition, alcohol is a contributory factor to deaths from accidents, which also show a pronounced socio-economic gradient.

Report of Diabetes Review Steering Group

DHSSPS has published the findings of the Report of the Steering Group chaired by the Chief Medical officer examining services for people with diabetes. The report assesses progress against the objectives of the original CREST/Diabetes UK Joint Taskforce Report (2003). åÊThere is an overview of the epidemiology of the condition as well as an assessment of current service provision, identified gaps and emergent priorities.

Strategies to promote translational research within the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Group: a report from the Translational Research Subcommittee.

Head and neck squamous cell cancer (HNSCC) is the sixth leading cause of cancer-related deaths worldwide. These tumors are commonly diagnosed at advanced stages and mortality rates remain high. Even cured patients suffer the consequences of aggressive treatment that includes surgery, chemotherapy, and radiotherapy. In the past, in clinical trials, HNSCC was considered as a single disease entity. Advances in molecular biology with the development of genomic and proteomic approaches have demonstrated distinct prognostic HNSCC patient subsets beyond those defined by traditional clinical-pathological factors such as tumor subsite and stage [Cho W (ed). An Omics Perspective on Cancer Research. New York/Berlin: Springer 2010]. Validation of these biomarkers in large prospective clinical trials is required before their clinical implementation. To promote this research, the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Program will develop the following strategies-(i) biobanking: prospective tissue collection from uniformly treated patients in the setting of clinical trials; (ii) a group of physicians, physician-scientists, and EORTC Headquarters staff devoted to patient-oriented head and neck cancer research; (iii) a collaboration between the basic scientists of the Translational Research Division interested in head and neck cancer research and the physicians of the Head and Neck Cancer Group; and (iv) funding through the EORTC Grant Program and the Network Core Institutions Consortium. In the present report, we summarize our strategic plans to promote head and neck cancer research within the EORTC framework.

Simulium (Psaroniocompsa) tergospinosum new species (Diptera: Simuliidae) in siolii group from the southern part of the State of Amazonas, Brazil

The larva, pupa, male and female of Simulium tergospinosum n. sp. are described and illustrated. The adults of this new species share many characters with species in the subgenus Psaroniocompsa, where it is placed. The larva of this species bears dorsal and lateral triangular tubercles on the abdomen and multiply branched scale-like setae on the body, suggesting that it belongs to the S. siolii species group. S. tergospinosum n.sp. was collected along the Juma River, Apuí county, in the southern part of the State of Amazonas, Brazil. The Juma, a black-water river, is a tributary of the Aripuanã River in the Madeira River hydrographic basin, on the southern part of Amazonas. Females were collected biting humans along the water courses during the sampling period (in the dry season).

Paper 3: EUROCAT data quality indicators for population-based registries of congenital anomalies.

The European Surveillance of Congenital Anomalies (EUROCAT) network of population-based congenital anomaly registries is an important source of epidemiologic information on congenital anomalies in Europe covering live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly. EUROCAT's policy is to strive for high-quality data, while ensuring consistency and transparency across all member registries. A set of 30 data quality indicators (DQIs) was developed to assess five key elements of data quality: completeness of case ascertainment, accuracy of diagnosis, completeness of information on EUROCAT variables, timeliness of data transmission, and availability of population denominator information. This article describes each of the individual DQIs and presents the output for each registry as well as the EUROCAT (unweighted) average, for 29 full member registries for 2004-2008. This information is also available on the EUROCAT website for previous years. The EUROCAT DQIs allow registries to evaluate their performance in relation to other registries and allows appropriate interpretations to be made of the data collected. The DQIs provide direction for improving data collection and ascertainment, and they allow annual assessment for monitoring continuous improvement. The DQI are constantly reviewed and refined to best document registry procedures and processes regarding data collection, to ensure appropriateness of DQI, and to ensure transparency so that the data collected can make a substantial and useful contribution to epidemiologic research on congenital anomalies.

Natural immunoglobulins (contribution to a debate on biomedical education)

Immunology has contributed to biomedical education in many important ways since the creation of scientific medicine in the last quarter of the 19th century. Today, immunology is a major area of biomedical research. Nevertheless, there are many basic problems unresolved in immunological activities and phenomena. Solving these problems is probably necessary to devise predictable and safe ways to produce new vaccines, treat allergy and autoimmune diseases and perform safe transplants. This challenge involves not only technical developments but also changes in attitude, of which the most fundamental is to abandon the traditional stimulus-response perspective in favor of more "systemic" views. Describing immunological activities as the operation of a complex multiconnected network, raises biological and epistemological issues not usually dealt with in biomedical education. Here we point to one example of systemic approaches. A new form of immunoblot (Panama blot), by which the reaction of natural immunoglobulins with complex protein mixtures may be analyzed by a special software and multivariate statistics, has been recently used to characterize human autoimmune diseases. Our preliminary data show that Panama blots can also be used to characterize global (systemic) immunogical changes in chronic human parasitic diseases, such as malaria and schistosomiasis mansoni, that correlate with the clinical status.

Impact of helpers on colony productivity in a primitively eusocial bee

Small societies of totipotent individuals are good systems in which to study the costs and benefits of group living that are central to the origin and maintenance of eusociality. For instance, in eusocial halictid bees, some females remain in their natal nest to help rear the next brood. Why do helpers stay in the nest? Do they really help, and if yes, is their contribution large enough to voluntarily forfeit direct reproduction? Here, we estimate the impact of helpers on colony survival and productivity in the sweat bee Halictus scabiosae. The number of helpers was positively associated with colony survival and productivity. Colonies from which we experimentally removed one helper produced significantly fewer offspring. However, the effect of helper removal was very small, on average. From the removal experiment, we estimated that one helper increased colony productivity by 0.72 additional offspring in colonies with one to three helpers, while the increase was smaller and not statistically significant in larger colonies. We conclude that helpers do actually help in this primitively eusocial bee, particularly in small colonies. However, the resulting increase in colony productivity is low, which suggests that helpers may be constrained in their role or may attempt to reproduce.