The association between muscle strength and activity limitations in patients with the hypermobility type of Ehlers–Danlos syndrome : the impact of proprioception

Purpose: The patients diagnosed with Ehlers-Danlos Syndrome Hypermobility Type (EDS-HT) are characterized by pain, proprioceptive inacuity, muscle weakness, potentially leading to activity limitations. In EDS-HT, a direct relationship between muscle strength, proprioception and activity limitations has never been studied. The objective of the study was to establish the association between muscle strength and activity limitations and the impact of proprioception on this association in EDS-HT patients. Methods: Twenty-four EDS-HT patients were compared with 24 controls. Activity limitations were quantified by Health Assessment Questionnaire (HAQ), Six-Minute Walk test (6MWT) and 30-s chair-rise test (30CRT). Muscle strength was quantified by handheld dynamometry. Proprioception was quantified by movement detection paradigm. In analyses, the association between muscle strength and activity limitations was controlled for proprioception and confounders. Results: Muscle strength was associated with 30CRT (r = 0.67, p = <0.001), 6MWT (r = 0.58, p = <0.001) and HAQ (r = 0.63, p = <0.001). Proprioception was associated with 30CRT (r = 0.55, p <0.001), 6MWT (r = 0.40, p = <0.05) and HAQ (r = 0.46, p < 0.05). Muscle strength was found to be associated with activity limitations, however, proprioceptive inacuity confounded this association. Conclusions: Muscle strength is associated with activity limitations in EDS-HT patients. Joint proprioception is of influence on this association and should be considered in the development of new treatment strategies for patients with EDS-HT. Implications for rehabilitation : Reducing activity limitations by enhancing muscle strength is frequently applied in the treatment of EDS-HT patients. Although evidence regarding treatment efficacy is scarce, the current paper confirms the rationality that muscle strength is an important factor in the occurrence of activity limitations in EDS-HT patients. Although muscle strength is the most dominant factor that is associated with activity limitations, this association is confounded by proprioception. In contrast to common belief proprioception was not directly associated with activity limitations but confounded this association. Controlling muscle strength on the bases of proprioceptive input may be more important for reducing activity limitations than just enhancing sheer muscle strength

Stimulation of poliovirus RNA synthesis and virus maturation in a HeLa cell-free in vitro translation-RNA replication system by viral protein 3CD(pro)

Poliovirus protein 3CD(pro )possesses both proteinase and RNA binding activities, which are located in the 3C(pro )domain of the protein. The RNA polymerase (3D(pol)) domain of 3CD(pro )modulates these activities of the protein. We have recently shown that the level of 3CD(pro )in HeLa cell-free in vitro translation-RNA replication reactions is suboptimal for efficient virus production. However, the addition of either 3CD(pro )mRNA or of purified 3CD(pro )protein to in vitro reactions, programmed with viral RNA, results in a 100-fold increase in virus yield. Mutational analyses of 3CD(pro )indicated that RNA binding by the 3C(pro )domain and the integrity of interface I in the 3D(pol )domain of the protein are both required for function. The aim of these studies was to determine the exact step or steps at which 3CD(pro )enhances virus yield and to determine the mechanism by which this occurs. Our results suggest that the addition of extra 3CD(pro )to in vitro translation RNA-replication reactions results in a mild enhancement of both minus and plus strand RNA synthesis. By examining the viral particles formed in the in vitro reactions on sucrose gradients we determined that 3CD(pro )has only a slight stimulating effect on the synthesis of capsid precursors but it strikingly enhances the maturation of virus particles. Both the stimulation of RNA synthesis and the maturation of the virus particles are dependent on the presence of an intact RNA binding site within the 3C(pro )domain of 3CD(pro). In addition, the integrity of interface I in the 3D(pol )domain of 3CD(pro )is required for efficient production of mature virus. Surprisingly, plus strand RNA synthesis and virus production in in vitro reactions, programmed with full-length transcript RNA, are not enhanced by the addition of extra 3CD(pro). Our results indicate that the stimulation of RNA synthesis and virus maturation by 3CD(pro )in vitro is dependent on the presence of a VPg-linked RNA template

Potential Use of Antiviral Agents in Polio Eradication

These compounds may serve as starting points for the design of more potent poliovirus inhibitors

Historia y futuro de poliovaccinación, una cuenta personal

Immunization against poliomyelitis began in the fifties of the previous century, with the development of a formalin-inactivated poliovirus vaccine (IPV). Shortly later, a live attenuated oral poliovirus vaccine (OPV) was developed. It has been shown that both vaccines are very effective, but they achieve success in different ways. The virus causing the disease, i.e. poliovirus, has been and is still the most extensively studied virus in the world. In the eighties of the previous century, the complete genomes of several poliovirus strains have been sequenced and the capsid structure has been elucidated at the atomic level. These scientific break-throughs of modern molecular genetics and immunology have opened the way for the development for new or alternative vaccines. Consequently, different innovative approaches were undertaken to develop better vaccines, in order to improve the control of poliomyelitis. Some of these developments, such as the capsid stabilisation of the OPV and the use of subviral particles produced in yeast as an alternative vaccine, will be discussed. The eradication programme of WHO will be discussed with an open mind to questions such as: (1) Is eradication possible? (2) Which vaccine should be used for the eradication? (3) Can we ever stop poliovaccination? (4) What is the impact of bioterrorism on poliovaccination policy?La inmunización contra la poliomielitis comienza en los años cincuenta del siglo pasado con el desarrollo de la vacuna de la polio inactivada (IPV). Inmediatamente después se desarrolló una vacuna oral polio trivalente (OPV). Se ha demostrado que ambas vacunas son muy efectivas, pero que alcanzan su objetivo de diferentes maneras. El virus causante de la enfermedad, es decir, el virus de la polio, ha sido y sigue siendo el virus más extensamente estudiado en el mundo. En los años ochenta del siglo anterior se logró secuenciar el genoma completo de varios tipos del virus de la polio, así como la elucidación a nivel atómico de la estructura de su cápside. Los avances científicos en genética molecular moderna e inmunología han abierto el camino para el desarrollo de nuevas o alternativas vacunas. Una de las consecuencias es el desarrollo de técnicas innovadoras para la creación de vacunas más perfeccionadas con el fin de mejorar el control sobre la poliomielitis. Algunos de estos desarrollos van a ser discutidos como, por ejemplo, la estabilización de la cápside en la OPV o el uso como vacuna alternativa de partículas subvirales producidas en levaduras. El programa de erradicación de la OMS (Organización Mundial de la Salud) va a ser discutido, prestando una especial atención a preguntas como las siguientes: — ¿Es posible la erradicación? — ¿Qué vacuna debería usarse para la erradicación? — ¿Podremos parar algún día la vacunación contra la polio? — ¿Cuál es el impacto del bioterrorismo en la política de vacunación de la polio

The 2011 PHARMINE report on pharmacy and pharmacy education in the European Union

The PHARMINE consortium consists of 50 universities from European Union member states or other European countries that are members of the European Association of Faculties of Pharmacy (EAFP). EU partner associations representing community (PGEU), hospital (EAHP) and industrial pharmacy (EIPG), together with the European Pharmacy Students´ Association (EPSA) are also part of the consortium. The consortium surveyed pharmacies and pharmacists in different settings: community, hospital, industry and other sectors. The consortium also looked at how European Union higher education institutions and courses are organised. The PHARMINE survey of pharmacy and pharmacy education in Europe produced country profiles with extensive information for EU member states and several other European countries. These data are available at: http://www.pharmine.org/losse_paginas/Country_Pr ofiles/. This 2011 PHARMINE report presents the project and data, and some preliminary analysis on the basic question of how pharmacy education is adapted to pharmacy practice in the EU.El consorcio PHARMINE se compone de 50 universidades de estados miembros de la Unión Europea que son miembros de la Asociación Europea de Facultades de Farmacias (EAFP). También hacen parte del consorcio asociaciones representando a las farmacias comunitarias (PGEU), hospitalarias (EAHP), e industrias (EIPG), así como la Asociación Europea de Estudiantes de Farmacia (EPSA). El Consorcio encuestó a farmacias y farmacéuticos en diferentes ámbitos: comunidad, hospital, industria y otros sectores. El consorcio también revisó como se organizan las instituciones de educación superior y los cursos en la Unión Europea. El cuestionario PHARMINE de farmacia y educación farmacéutica en Europa produjo perfiles de países con información exhaustiva de los estados miembros de la UE y otros países europeos. Estos datos están disponibles en http://www.pharmine.org/losse_paginas/Country_P rofiles/. Este Informe PHARMINE 2011 presenta el proyecto y los datos, y algunos análisis preliminares sobre la cuestión básica de cómo se adapta la educación farmacéutica a la práctica de la farmacia en la UE

The PHARMINE study on the impact of the European Union directive on sectoral professions and of the Bologna declaration on pharmacy education in Europe

The Bologna declaration and the European Union (EU) directive 2005/36/EC on the recognition of professional qualifications influence the mobility of pharmacy students and pharmacy professionals, respectively. In addition the Bologna declaration aims at tuning higher education degrees including pharmacy throughout the EU in order to prepare for a harmonised European Higher Education Area. The directive outlines the knowledge, skills and qualifications required for the pursuit of the professional activity of a pharmacy in the EU. The PHARMINE project (Pharmacy Education in Europe, www.pharmine.org) looked at how the Bologna declaration and the directive influence modern-day pharmacy education and training in Europe.La Declaración de Boloña y la Directiva de la Unión Europea (UE) 2005/36/EC sobre reconocimiento de cualificaciones profesionales influencian la movilidad de los estudiantes de Farmacia y de los profesionales farmacéuticos, respectivamente. Además, la Declaración de Boloña trata de sintonizar los grados de educación superior, incluyendo el de farmacia, en toda la UE para crear un Espacio Común de Educación Superior Europeo. La Directiva señala los conocimientos, habilidades y cualificaciones requeridos para el ejercicio profesional de la farmacia en la UE. El proyecto PHARMINE (Pharmacy Education in Europe, www.pharmine.org) revise como la Declaración de Boloña y la Directiva influencian la educación y la formación modernas de la farmacia en Europa

A comparison of WIN 51711 and R 78206 as stabilizers of poliovirus virions and procapsids

The thermal denaturation of poliovirus virions and procapsids in the 42 to 48 °C range was studied using N- and H-specific monocional antibodies. The half-life of the N antigen of Mahoney and Sabin 1 virions was extended 50- to 250-fold by either 10 ~tM WIN 51711 or R 78206. The minimum concentrations required for full stabilization at 46 °C (1-0 ~tM for WIN 51711, 0-2 g~,l for R 78206) were independent of the strain or serotype of the virus; 30 to 60 molecules of stabilizer per virion were required for full protection. R 78206 was the most efficient stabilizer of Mahoney procapsids; the half-life of the N-specific epitopes of these particles at 44 *C was extended from less than 1 min to 1 day