Electron cryo-microscopy reveals mechanism of action of propranolol on artificial membranes.

The pharmacological activity of several amphiphilic drugs is often related to their ability to interact with biological membranes. Propranolol is an efficient multidrug resistance (MDR) modulator; it is a nonselective beta-blocker and is thought to reduce hypertension by decreasing the cardiac frequency and thus blood pressure. It is used in drug delivery studies in order to treat systemic hypertension. We are interested in the interaction of propranolol with artificial membranes, as liposomes of controllable size are used as biocompatible and protective structures to encapsulate labile molecules, such as proteins, nucleic acids or drugs, for pharmaceutical, cosmetic or chemical applications. We present here a study of the interaction of propranolol, a cationic surfactant, with pure egg phosphatidylcholine (EPC) vesicles. The gradual transition from liposome to micelle of EPC vesicles in the presence of propranolol was monitored by time-resolved electron cryo-microscopy (cryo-EM) under different experimental conditions. The liposome-drug interaction was studied with varying drug/lipid (D/L) ratios and different stages were captured by direct thin-film vitrification. The time-series cryo-EM data clearly illustrate the mechanism of action of propranolol on the liposome structure: the drug disrupts the lipid bilayer by perturbing the local organization of the phospholipids. This is followed by the formation of thread-like micelles, also called worm-like micelles (WLM), and ends with the formation of spherical (globular) micelles. The overall reaction is slow, with the process taking almost two hours to be completed. The effect of a monovalent salt was also investigated by repeating the lipid-surfactant interaction experiments in the presence of KCl as an additive to the lipid/drug suspension. When KCl was added in the presence of propranolol the overall reaction was the same but with slower kinetics, suggesting that this monovalent salt affects the general lipid-to-micelle transition by stabilizing the membrane, presumably by binding to the carbonyl chains of the phosphatidylcholine.

Evaluation of rapid alternative methods for drug susceptibility testing in clinical isolates of Mycobacterium tuberculosis

A study was carried out to compare the performance of a commercial method (MGIT) and four inexpensive drug susceptibility methods: nitrate reductase assay (NRA), microscopic observation drug susceptibility (MODS) assay, MTT test, and broth microdilution method (BMM). A total of 64 clinical isolates of Mycobacterium tuberculosis were studied. The Lowenstein-Jensen proportion method (PM) was used as gold standard. MGIT, NRA, MODS, and MTT results were available on an average of less than 10 days, whereas BMM results could be reported in about 20 days. Most of the evaluated tests showed excellent performance for isoniazid and rifampicin, with sensitivity and specificity values > 90%. With most of the assays, sensitivity for ethambutol was low (62-87%) whereas for streptomycin, sensitivity values ranged from 84 to 100%; NRA-discrepancies were associated with cultures with a low proportion of EMB-resistant organisms while most discrepancies with quantitative tests (MMT and BMM) were seen with isolates whose minimal inhibitory concentrations fell close the cutoff. MGIT is reliable but still expensive. NRA is the most inexpensive and easiest method to perform without changing the organization of the routine PM laboratory performance. While MODS, MTT, and BMM, have the disadvantage from the point of view of biosafety, they offer the possibility of detecting partial resistant strains. This study shows a very good level of agreement of the four low-cost methods compared to the PM for rapid detection of isoniazid, rifampicin and streptomycin resistance (Kappa values > 0.8); more standardization is needed for ethambutol.

The untranslated regions of genes from Trypanosoma cruzi: perspectives for functional characterization of strains and isolates

The sequencing of Trypanosoma cruzi genome has been completed and a great deal of information is now available. However, the organization of protozoa genomes is somewhat elusive and much effort must be applied to reveal all the information coded in the nucleotide sequences. Among the DNA segments that needs further investigation are the untranslated regions of genes. Many of the T. cruzi genes that were revealed by the genome sequencing lack information about the untranslated regions. In this paper, some features of these untranslated segments as well as their applications in T. cruzi populations are discussed.

NI Registry of Self-harm Annual Report 2012/13

The purpose of the registry is to improve understanding about self-harm and related behaviours in Northern Ireland. The information gathered will be used to monitor trends and patterns over time and, perhaps most importantly, will help shape the development of services and support to meet need. The information will also help provide trusts and the Department of Health, Social Services and Public Safety with a more accurate understanding of the impact of self-harm on Emergency Departments.

Discursive media strategies in the journalistic construction of schistosomiasis in Jaboticatubas, Minas Gerais

Using media discourse analysis for material published by the press on schistomisasis in the city of Jaboticatubas, the possible determining factors of narrative and discursive constructions in the diffusion of information are discussed. It was observed that media discourse treats schistosomiasis in 1962 as something from the natural order. By 1997 and 1998, the media discourse strategies reveal ideological treatment in favor of certain social segments. Situations are identified in which social agents in specific contexts construct the meanings of this endemic disease. It was concluded that the economic organization of space was a determining factor in the production and circulation of the media discourses.

Electron microscopy of trypanosomes: a historical view

Since the discovery of the electron microscope and the development of the initial techniques for the processing of biological samples for electron microscopy, the protozoan Trypanosoma cruzi has been the subject of intense investigation. This review analyzes the results obtained by observation of whole trypanosomes as well as thin sections and replicas using several microscopic approaches. Micrographs detailing the appearance of T. cruzi using several methods illustrate the evolution of electron microscopic techniques as well as its contribution to understanding the structural organization of the protozoan.

Estudio comparativo de la calidad de la información ofrecida sobre los servicios en las webs de las bibliotecas virtuales de universidades a distancia

S'exposa el resultat d'un estudi comparatiu sobre la comunicació web dels serveis de les biblioteques virtuals universitàries d'una selecció d'universitats a distància entre les quals hi ha la UNED, la UOC i l'Open University. Aquest estudi es fa observant les diferències qualitatives de diversos aspectes, com ara l'organització, l'accessibilitat, els formats, el redactat, la utilitat i la presentació de la informació sobre els serveis de la biblioteca oferta en la web als usuaris d'aquelles universitats i/o Biblioteques que han realitzat el procés de gestió de qualitat o han confeccionat la carta de serveis i les que no. Entre diverses recomanacions i exemples de bones pràctiques, l'estudi conclou que les universitats i biblioteques que no mostren cap tipus de procés de qualitat en la seva institució podem veure que són les que obliden alguns elements essencials i molts detalls pel que fa a la descripció de la oferta de serveis es refereix. Conclusió i recomanacions extensibles a qualsevol biblioteca universitària que ofereixi informació en línia sobre els seus serveis. A partir de l'elaboració de fitxes que recullen els diversos aspectes a observar de cadascuna de les biblioteques hem ponderat, d'acord amb la diversa bibliografia consultada, cadascun com desaconsellable, recomanable i excel·lent amb el resultat d'un informe que mostra totes les recomanacions per a cadascun dels elements.

E-MOVE project : a case of successfulcooperation of European academic librariesof distance teaching universities

El Library and Learning Support Working Group (LLSWG) és una xarxa europea de professionals de biblioteca i de la informació i educadors dins de l'Associació Europea d'Universitats d'Ensenyament (EADTU). EADTU és l'organització que representa tant les universitats obertes i d'ensenyament a distància com els consorcis nacionals d'institucions d'ensenyament superior actius en els camps d'educació de distància i e-learning. El 2005 l'Associació Europea d'Universitats d'Ensenyament de Distància (EADTU) presentava a la Comissió Europea una proposta de projecte sobre Mobilitat Virtual anomenada E-MOVE. El projecte incloïa, entre d'altres, un paquet de treball referent a biblioteca i suport a l'aprenentatge al context de mobilitat virtual. Aquest fou desenvolupat pel LLSWG de l'EADTU.

Usos y formas de la biblioteca virtual en la educación a distancia

L'ús de les noves tecnologies de la informació ha fet possible la creació de biblioteques virtuals universitàries que, no solament són part integrant del model pedagògic, sinó que poden introduir els seus continguts i serveis en llocs fins ara insospitats: a les aules virtuals formant parteix de les assignatures, en els espais virtuals de suport a la docència, en les àrees de recerca i, sens dubte, en l'apartat de Biblioteca que li és propi. Aquestes facilitats derivades de l'organització de Campus Virtuals, permeten al professional bibliotecari/documentalista personalitzar continguts i serveis, i crear biblioteques a mida de cada necessitat. També permeten desenvolupar tècniques "push" per notificar i disseminar els serveis més adequats a cada tipologia d'usuari.

La organización de recursos digitales y la oferta de servicios documentales en un entorno virtual de aprendizaje

El creixement d'usuaris potencials i el de l'oferta de serveis per part de la Biblioteca Virtual de l'UOC, va generar un procés de reflexió estratègica per donar resposta a nou escenari de l'organització. El resultat ha estat tres eixos o línies d'actuació que permetin afrontar aquest canvi i creixement: organització dels recursos en una base de dades, el desenvolupament dels serveis "push" i el facilitar l'accés a la biblioteca des de qualsevol entorn i de forma personalitzada a aquest.

M-Library in an m-University : changing Models in the Open University of Catalonia

The general perspective of M-technologies and M-Services at the Spanish universities is not still in a very high level when we are ending the first decade of the 21st century. Some Universities and some of their libraries are starting to try out with M-technologies, but are still far from a model of massive exploitation, less than in some other countries. A deep study is needed to know the main reasons, study that we will not do in this paper. This general perspective does not mean that there are no significant initiatives which start to trust in M-technologies from Universities and their libraries. Models based in M-technologies make more sense than ever in open universities and in open libraries. That's the reason why the UOC's Library began in late 90s its first experiences in the M-Technologies and M-Libraries developments. In 1999 the appropriate technology offered the opportunity to carry out the first pilot test with SMS, and then applying the WAP technology. At those moments we managed to link-up mobile phones to the OPAC through a WAP system that allowed searching the catalogue by categories and finding the final location of a document, offering also the address of the library in which the user could loan it. Since then, UOC (and its library) directs its efforts towards adapting the offer of services to all sorts of M-devices used by end users. Left the WAP technology, nowadays the library is experimenting with some new devices like e-books, and some new services to get more feedback through the OPAC and metalibrary search products. We propose the case of Open University of Catalonia, in two levels: M-services applied in the library and M-technologies applied in some other university services and resources.

Brazilian contribution for a better knowledge on the biology of Toxoplasma gondii

Historically, scientists in Brazil has significantly contributed to the biology, cultivation and structural organization of the pathogenic protozoan Toxoplasma gondiiand its interaction with host cells, starting with the description of the protozoan by Splendore in 1908. The intracellular and extracellular corpuscoli observed in rabbits, corresponded to what we now as tachyzoites. Later on, a pioneering method to grow T. gondii in tissue cultures was developed by Guimarães and Meyer, 1942. They also observed for the first time T. gondii by transmission electron microscopy and made the initial description of the cytoskeleton of T. gondii by observing negatively stained cells. In the 1980's, the relation of the cytoskeleton with the sub-pellicular microtubules was reveled by freeze-fracture. More recently, several Brazilian groups have analyzed in detail basic aspects of the early interaction of the protozoan with the host cell, such as the role of protein phosphorylation, transfer of host cell surface components to the protozoan and genesis and organization of the parasitophorous vacuole. Tachyzoites strategically inhibit nitric oxide production during active invasion of activated macrophages. In vitro studies on the sexual cycle of T. gondii using primary cultures of cat enterocytes and the egress from host cells are being carried out. Perspectives are that the contribution of Brazilian science to the knowledge on T. gondii biology will continue to flourish in years to come.

Phylogenetic analysis of Biomphalaria tenagophila (Orbigny, 1835) (Mollusca: Gastropoda)

Mitochondrial DNA of Biomphalaria tenagophila, a mollusc intermediate host of Schistosoma mansoni in Brazil, was sequenced and characterised. The genome size found for B. tenagophila was 13,722 bp and contained 13 messenger RNAs, 22 transfer RNAs (tRNA) and two ribosomal RNAs (rRNA). In addition to sequencing, the mitochondrial DNA (mtDNA) genome organization of B. tenagophila was analysed based on its content and localization of both coding and non-coding regions, regions of gene overlap and tRNA nucleotide sequences. Sequences of protein, rRNA 12S and rRNA 16S nucleotides as well as gene organization were compared between B. tenagophila and Biomphalaria glabrata, as the latter is the most important S. mansoni intermediate host in Brazil. Differences between such species were observed regarding rRNA composition. The complete sequence of the B. tenagophila mitochondrial genome was deposited in GenBank (accession EF433576). Furthermore, phylogenetic relationships were estimated among 28 mollusc species, which had their complete mitochondrial genome deposited in GenBank, using the neighbour-joining method, maximum parsimony and maximum likelihood bootstrap. B. tenagophila was positioned at a branch close to B. glabrata and Pulmonata molluscs, collectively comprising a paraphyletic group, contrary to Opistobranchia, which was positioned at a single branch and constituted a monophyletic group.

Factors influencing interprofessional practices of physiotherapists working in private settings with people with low back pain: a qualitative study

Purpose: Collaboration and interprofessional practices are highly valued in health systems everywhere, partly based on the rationale that they improve outcomes of care for people with complex health problems, such as low back pain. Research in the area of low back pain also supports the involvement of different health professionals in the interventions for people who present this condition. The aim of this studywas to identify factors influencing the interprofessional practices of physiotherapists working in private settings with people with low back pain. Relevance: Physiotherapists, like other health professionals, are encouraged to engage in interprofessional practices in their dailywork. However, to date, very little is known of their interprofessional practices, especially in private settings. Understanding physiotherapists' interprofessional practices and their influencing factors will notably advance knowledge relating to the organisation of physiotherapy services for people with low back pain. Participants: Participants in this study were 13 physiotherapists including 10 women and 3 men, having between 3 and 22 years of professional experience, and working in one of 10 regions of the Province of Quebec (Canada). In order to obtain maximal variation in the perspectives, participants were selected using a recruitment matrix including three criteria: duration of professional experience, work location, and physical proximity with other professionals. Methods: Thiswas a descriptive qualitative study using faceto- face semi-structured interviews as the main method of data collection. An interview guide was developed based on an evidence-derived frame of reference. Each interview lasted between 55 and 95 minutes and was transcribed verbatim. Analysis: Qualitative analyses took the form of content analysis, encompassing data coding and general thematic regrouping. NVivo version 8 was used to assist data organisation and analysis. Results: Multiple factors influencing the interprofessional practices of physiotherapists were identified. The main factors include the consulting person's health condition, the extent of knowledge on health professionals' roles and fields of practice, the proximity and availability of professional resources, as well as daily work schedules. Conclusions: Our findings highlight the influence of multiple factors on physiotherapists' interprofessional practices, including professional practice and organisational issues. However, further research on the interprofessional practices of physiotherapists is still required. Research priorities targeting the views of other health professionals, as well as those of services users, would enhance our comprehension of interprofessional practices of physiotherapists. Implications: This study provides new insights that improve our understanding of the interprofessional practices of physiotherapists working in private settings with people with low back pain, more specifically on the factors influencing these practices. Based on our findings, implementing changes such as improving current and future health professionals' knowledge of the fields and roles of other health professionals through training may contribute to positively influencing interprofessional practices. Keywords: Interprofessional practices; Private practice; Low back pain Funding acknowledgements: This research was supported in part by a B.E. Schnurr Memorial Fund Research Grant administered by the Physiotherapy Foundation of Canada, as well as from a clinical research partnership in physiotherapy between the Quebec Rehabilitation Research Network (REPAR) and the Ordre professionnel de la physiothérapie du Québec (OPPQ). KP received doctoral-level scholarships from the Canadian Institutes of Health Research (CIHR) and the Institut de recherche Robert-Sauvé en santé et en sécurité du travail (IRSST). CE Dionne is a FRSQ senior Research Scholar. Ethics approval: This project was approved by the ethics research committee of the Institut de réadaptation en déficience physique de Québec.