17 The epidemiology and immunogenetics of IDDM in Italian-heritage populations. Diabetes Epidemiology Research International (DERI) Study Group

in Diabetes/Metabolism Reviews (1990), 6

2-Octadecynoic acid as a dual life stage inhibitor of Plasmodium infections and plasmodial FAS-II enzymes

in Bioorganic & Medicinal Chemistry Letters (2014), 24(17), 4151-4157

The malaria parasite Plasmodium goes through two life stages in the human host, a non-symptomatic liver stage (LS) followed by a blood stage with all clinical manifestation of the disease. In this study ... [more ▼]

The malaria parasite Plasmodium goes through two life stages in the human host, a non-symptomatic liver stage (LS) followed by a blood stage with all clinical manifestation of the disease. In this study, we investigated a series of 2-alkynoic fatty acids (2-AFAs) with chain lengths between 14 and 18 carbon atoms for dual in vitro activity against both life stages. 2-Octadecynoic acid (2-ODA) was identified as the best inhibitor of Plasmodium berghei parasites with ten times higher potency (IC50 = 0.34 μg/ml) than the control drug. In target determination studies, the same compound inhibited three Plasmodium falciparum FAS-II (PfFAS-II) elongation enzymes PfFabI, PfFabZ, and PfFabG with the lowest IC50 values (0.28-0.80 μg/ml, respectively). Molecular modeling studies provided insights into the molecular aspects underlying the inhibitory activity of this series of 2-AFAs and a likely explanation for the considerably different inhibition potentials. Blood stages of P. falciparum followed a similar trend where 2-ODA emerged as the most active compound, with 20 times less potency. The general toxicity and hepatotoxicity of 2-AFAs were evaluated by in vitro and in vivo methods in mammalian cell lines and zebrafish models, respectively. This study identifies 2-ODA as the most promising antiparasitic 2-AFA, particularly towards P. berghei parasites. © 2014 Elsevier Ltd. All rights reserved. [less ▲]

A phenotypic screen in zebrafish identifies a novel small-molecule inducer of ectopic tail formation suggestive of alterations in non-canonical Wnt/PCP signaling

in PLoS ONE (2013), 8(12),

Zebrafish have recently emerged as an attractive model for the in vivo bioassay-guided isolation and characterization of pharmacologically active small molecules of natural origin. We carried out a ... [more ▼]

Zebrafish have recently emerged as an attractive model for the in vivo bioassay-guided isolation and characterization of pharmacologically active small molecules of natural origin. We carried out a zebrafish-based phenotypic screen of over 3000 plant-derived secondary metabolite extracts with the goal of identifying novel small-molecule modulators of the BMP and Wnt signaling pathways. One of the bioactive plant extracts identified in this screen - Jasminum gilgianum, an Oleaceae species native to Papua New Guinea - induced ectopic tails during zebrafish embryonic development. As ectopic tail formation occurs when BMP or non-canonical Wnt signaling is inhibited during the tail protrusion process, we suspected a constituent of this extract to act as a modulator of these pathways. A bioassay-guided isolation was carried out on the basis of this zebrafish phenotype, identifying para-coumaric acid methyl ester (pCAME) as the active compound. We then performed an in-depth phenotypic analysis of pCAME-treated zebrafish embryos, including a tissue-specific marker analysis of the secondary tails. We found pCAME to synergize with the BMP-inhibitors dorsomorphin and LDN-193189 in inducing ectopic tails, and causing convergence-extension defects in compound-treated embryos. These results indicate that pCAME may interfere with non-canonical Wnt signaling. Inhibition of Jnk, a downstream target of Wnt/PCP signaling (via morpholino antisense knockdown and pharmacological inhibition with the kinase inhibitor SP600125) phenocopied pCAME-treated embryos. However, immunoblotting experiments revealed pCAME to not directly inhibit Jnk-mediated phosphorylation of c-Jun, suggesting additional targets of SP600125, and/or other pathways, as possibly being involved in the ectopic tail formation activity of pCAME. Further investigation of pCAME's mechanism of action will help determine this compound's pharmacological utility. © 2013 Gebruers et al. [less ▲]

Absence of alpha 7 integrin in dystrophin-deficient mice causes a myopathy similar to Duchenne muscular dystrophy.

in Human molecular genetics (2006), 15(6), 989-98

Both the dystrophin-glycoprotein complex and alpha7beta1 integrin have critical roles in the maintenance of muscle integrity via the provision of mechanical links between muscle fibres and the basement ... [more ▼]

Both the dystrophin-glycoprotein complex and alpha7beta1 integrin have critical roles in the maintenance of muscle integrity via the provision of mechanical links between muscle fibres and the basement membrane. Absence of either dystrophin or alpha7 integrin results in a muscular dystrophy. To clarify the role of alpha7 integrin and dystrophin in muscle development and function, we generated integrin alpha7/dystrophin double-mutant knockout (DKO) mice. Surprisingly, DKO mice survived post-natally and were indistinguishable from wild-type, integrin alpha7-deficient and mdx mice at birth, but died within 24-28 days. Histological analysis revealed a severe muscular dystrophy in DKO mice with endomysial fibrosis and ectopic calcification. Weight loss was correlated with the loss of muscle fibres, indicating that progressive muscle wasting in the double mutant was most likely due to inadequate muscle regeneration. The data further support that premature death of DKO mice is due to cardiac and/or respiratory failure. The integrin alpha7/dystrophin-deficient mouse model, therefore, resembles the pathological changes seen in Duchenne muscular dystrophy and suggests that the different clinical severity of dystrophin deficiency in human and mouse may be due to a fine-tuned difference in expression of dystrophin and integrin alpha7 in both species. Together, these findings indicate an essential role for integrin alpha7 in the maintenance of dystrophin-deficient muscles. [less ▲]

Acceptability in food of NaCl/KCl mixture.

in Lancet (1983), 2(8364), 1427-8

Accompagner les détenus vers l'employabilité

in Echidistante Revue de Culture et Sciences (2009), 5-6(53-54), 147-164

Si les ex-détenus sont amenés à être, comme l’ensemble des citoyens européens, des acteurs de la compétitivité économique capables de répondre aux exigences du marché du travail, il est nécessaire qu'ils ... [more ▼]

Si les ex-détenus sont amenés à être, comme l’ensemble des citoyens européens, des acteurs de la compétitivité économique capables de répondre aux exigences du marché du travail, il est nécessaire qu'ils acquièrent ou améliorent pendant leur détention leurs compétences relatives à l’employabilité. Mais les personnels des établissements pénitentiaires sont-ils prêts à assumer cette nouvelle tâche? Dans le cadre du projet EQUAL-RESET « Réinsertion Économique et Sociale par l’Éducation et le Travail des détenus», des entretiens qualitatifs ont été menés auprès des personnels du Centre Pénitentiaire de Givenich (prison semi-ouverte au Grand-Duché du Luxembourg) afin de comprendre les difficultés qu’ils rencontrent dans l’accompagnement social et éducatif des détenus. Les personnels ont reconnu avoir peu de besoins en connaissances théoriques, mais ont souligné un manque de compétences réelles pour mieux: - s’adapter aux diversités culturelles et éducatives ; - réagir de façon plus adéquate face aux difficultés et aux efforts des détenus (positiver, valoriser le travail du détenu, être à l’écoute, se montrer patient, éduquer à la ponctualité, etc.) ; - travailler en équipe avec les collègues et les partenaires extérieurs afin de construire puis accompagner les projets personnalisés des détenus, ce dernier point étant le plus évoqué dans les discours des enquêtés. Pour qu'ils assument pleinement et efficacement leurs nouvelles missions d’encadrement, former le personnel des prisons doit être une priorité nationale. [less ▲]

Achieving Universal Health Coverage: Technology for innovative primary health care education

Report (2016)

The challenges to achieving universal health coverage (UHC) are obvious yet vast in their scope: leading these is a lack of strong primary health care (PHC) systems and a global shortage of well-trained ... [more ▼]

The challenges to achieving universal health coverage (UHC) are obvious yet vast in their scope: leading these is a lack of strong primary health care (PHC) systems and a global shortage of well-trained health care professionals. Addressing these challenges is paramount, as it is well-trained health care professionals who will build the strong PHC systems that are necessary for UHC. Due to the continuing spread and evolution of information and communications technology (ICT) in health care and education, ICT should be considered as an essential tool for innovative primary health care education.  Many nations face a distinct lack of UHC, grossly unequal health services and an acute shortage of suitably qualified family doctors, nurses and allied health care professionals that constitute the primary health care team. It is estimated that by 2035, the world will have a shortage of 12.9 million health care professionals, however an additional 1.9 billion people will require health care. Recruiting, educating and retaining these primary health care teams is therefore fundamental to meet ongoing demands.  Family doctors contribute to high quality, cost-effective and accessible primary health care. However, PHC faces considerable challenges, including a preference from policymakers, the public, and members of the health care community for specialisation. Specialist-focused care may be attractive, but it is often economically unsustainable and absorbs resources that are necessary for PHC. Yet, cooperation between primary and secondary care is essential for delivering the best care to patients and communities. It should not be a matter of choosing between primary and secondary care, but rather of recognising and adequately supporting the unique attributes and skillsets that each has to offer.  Family medicine lies at the heart of primary health care. The key to producing skilled family doctors is good family medicine training, particularly at a postgraduate level. There is great potential to improve the scale and quality of family medicine training, starting with exposure to the field as early as possible. For the delivery of primary care to be effective – and lead to the achievement of universal health coverage – the composition of the primary care team should reflect the demography and health needs of the local population. Thus, the composition of the primary care team will differ from location to location, depending on the age/sex/ health needs of the local population. Family doctors and all of the PHC professionals should have a set of universal core skills, in addition to skills specific to the population and geography they serve. To provide effective care, health professionals need to understand the importance of social factors in influencing population health; therefore, training curricula must be adapted to local contexts  Career development through postgraduate training strongly motivates health professionals to stay in their own localities, as well as being vital for patient safety and improved outcomes. Yet, despite a thirst for postgraduate training among family doctors and other primary health care professionals, it is often difficult to access. ICT may be used to address recruitment and retention issues by providing easily accessible and good quality education.  This report examines a key question: Can ICT facilitate the education of PHC professionals worldwide in order to address the challenges facing PHC and UHC? Through in-depth literature reviews, analysis, and targeted interviews with key experts, the report concludes that ICT can indeed support, enhance and accelerate the education of the primary health care team’s members, in six key ways:  1. It is an effective means of developing workforce capacity. By overcoming geographical barriers and supplementing traditional instruction with online delivery from international and regional tutors, ICT can substantially increase health care professionals’ access to postgraduate education without the need for travel, thus helping to avoid disruption to healthcare delivery.  2. It helps to recruit and retain professionals. E-learning overcomes issues of access and isolation, and can be done flexibly to suit the learner. By providing access to specialist support, postgraduate courses and mentoring opportunities, e-learning and telehealth encourage in-country and rural retention of health care workers.  3. It is cost-saving. Traditional models of health professional education are expensive, both for the provider and for health care professionals. Developing ICT solutions may entail high initial costs but these are reduced over time, and with more users, achieve economies of scale.  4. It facilitates social and collaborative learning which has been shown to have the greatest impact on patient outcomes. A blend of synchronous and asynchronous e-learning is likely to be the most effective way of achieving interprofessional learning. Communities of practice are encouraged using ICT and social media, reducing professional isolation and improving collaboration.  5. It can help to bring contextualised care to where it is needed. For example, simulation-based medical education enables problem-based, interactive and contextualised learning. End-user (including patient) participation is paramount when designing ICT-based educational programmes.  6. It improves the quality of care by facilitating access to evidence-based medicine and reflective learning. Email alerts can support education by reaching a large audience and providing trustworthy information tailored to individual needs; social media can aid in streamlining vast amounts of information into a small number of tailored-to-the-individual articles; blogs and electronic portfolios can encourage reflective life-long learning. Capturing these opportunities will require stakeholders to consider the following:  a) Securing political and financial support to establish and maintain strong PHC systems  b) Adopting a collaborative interprofessional approach between health professionals, from medical school through to the workplace  c) Providing education and training relevant to the context and to user needs  d) Improving recruitment and retention through training  e) Encouraging the standardisation and accreditation of health professional education  f) Investing in ICT training for learners, educators and patients  g) Planning and developing programmes that use technology meaningfully to improve care quality, cost-effectiveness, accessibility, equity and patient safety  h) Recognise and consolidate the interdependence of all the health professionals in the PHC setting.  [less ▲]

Activation of sphingosine-1-phosphate signalling as a potential underlying mechanism of the pleiotropic effects of statin therapy.

in Critical reviews in clinical laboratory sciences (2013), 50(3), 79-89

The mechanisms by which statins are beneficial are incompletely understood. While the lowering of low-density lipoprotein concentration is associated with regression of atherosclerosis, the observed ... [more ▼]

The mechanisms by which statins are beneficial are incompletely understood. While the lowering of low-density lipoprotein concentration is associated with regression of atherosclerosis, the observed benefit of statin therapy begins within months after its initiation, making regression an unlikely cause. Although LDL-C lowering is the main mechanism by which statin therapy reduces cardiovascular events, evidence suggests that at least some of the beneficial actions of statins may be mediated by their pleiotropic effects. Thus, statins may modulate the function of cardiovascular cells and key signalling proteins, including small G-proteins, to ultimately exert their pleiotropic effects. Sphingosine-1-phosphate (S1P) is a naturally occurring bioactive lysophospholipid that regulates diverse physiological functions in a variety of different organ systems. Within the cardiovascular system, S1P mediates cardioprotection following ischemia/reperfusion injury, anti-inflammatory response, improvement of endothelial function, increased mobilization and differentiation of endothelial progenitor cells, inhibition of oxidation, and anti-atherogenic and anti-thrombotic actions. Early evidence suggests that the pleiotropic effects of statins may be related to an increase in S1P signalling. This review focuses on S1P signalling as the potential mechanism underlying the pleiotropic effects of statins. An improved understanding of this mechanism may be vital for establishing the clinical relevance of statins and their importance in the treatment and prevention of coronary artery disease. Key points Several studies have demonstrated a benefit from lowering serum LDL-C with statins in patients with and without clinical evidence of CAD. These may be mediated by the pleiotropic effects of statins-the mechanisms of which are incompletely understood. Early evidence suggests that statins may increase S1P signalling pathways through upregulation of the expression of S1P receptors and an increase in plasma levels of S1P to ultimately exert their pleiotropic effects. Future clinical trials and basic science research aimed at the underlying mechanisms of the pleiotropic effects of statins should enlighten us to their relative clinical relevance and importance. [less ▲]

Active participation in preventionist professional practices: Questions to ergonomic training course.

Scientific Conference (2012, February)

Adaptation and validation of a telephone questionnaire serbian version for case detection of Rheumatoid Arthritis and Spondyloarthropathy (multicentric Eular study)

in Clinical and Experimental Rheumatology (2007), 25(1), 75-84