RESUMO
« International Medical Graduates ¼ (IMGs) are medical doctors practicing abroad, in a country where they have not studied. Their number is increasing at the global level as well as in Switzerland. In this article we describe the challenges faced by IMGs : difficulties related to issues in communication, differences in medical education, variations in clinical practice and difficulties in dealing with specific categories of patients because of local societal values. These challenges demand a process of professional and cultural transition from these foreign medical doctors who constitute a real asset for the host countries. Indeed, they participate in solving the problem of medical shortage and bring to their host country their rich professional experience and recognized clinical skills.
Les « Diplômés Internationaux en Médecine ¼ (DIM), médecins pratiquant leur métier dans un pays dans lequel ils n'ont pas étudié, sont en augmentation à l'échelle globale comme à l'échelle suisse. Dans cet article, nous décrivons les défis rencontrés par les DIM : aspects liés à la communication, différences dans la formation médicale, variations dans la pratique clinique et difficultés de prise en charge de catégories spécifiques de patients en lien avec certaines valeurs sociétales. Ces défis rendent nécessaire un processus de transition professionnelle et culturelle de ces médecins étrangers, qui représentent un réel atout pour les pays d'accueil. En effet, ils participent à résoudre les problèmes de pénurie et de déserts médicaux en apportant leur riche expérience professionnelle et des compétences cliniques reconnues.
Assuntos
Comunicação , Médicos Graduados Estrangeiros , Médicos , Demografia , Humanos , SuíçaRESUMO
The immunoglobulin heavy-chain variable region (IGHV) mutational status is a strong determinant of remission duration in chronic lymphocytic leukemia (CLL). The aim of this work was to compare the multidrug resistance (MDR) signature of IGHV mutated and unmutated CLL cells, identifying biochemical and molecular targets potentially amenable to therapeutic intervention.We found that the mevalonate pathway-dependent Ras/ERK1-2 and RhoA/RhoA kinase signaling cascades, and the downstream HIF-1α/P-glycoprotein axis were more active in IGHV unmutated than in mutated cells, leading to a constitutive protection from doxorubicin-induced cytotoxicity. The constitutive MDR phenotype of IGHV unmutated cells was partially dependent on B cell receptor signaling, as shown by the inhibitory effect exerted by ibrutinib. Stromal cells further protected IGHV unmutated cells from doxorubicin by upregulating Ras/ERK1-2, RhoA/RhoA kinase, Akt, HIF-1α and P-glycoprotein activities. Mevalonate pathway inhibition with simvastatin abrogated these signaling pathways and reversed the resistance of IGHV unmutated cells to doxorubicin, also counteracting the protective effect exerted by stromal cells. Similar results were obtained via the targeted inhibition of the downstream molecules ERK1-2, RhoA kinase and HIF-1α.Therefore, targeting the mevalonate pathway and its downstream signaling cascades is a promising strategy to circumvent the MDR signature of IGHV unmutated CLL cells.
