Training medical students in health promotion: twenty years of experience at the Faculty of Medicine of the University of Geneva.

In most cases, the work of medical doctors, be they general practitioners or specialists, involves some dimension of health promotion (HP). There is thus ample justification for increasing the awareness of medical students vis-à-vis HP and its relevance for their future practice. In the context of a major curriculum reform (problem-based learning [PBL]) at the Faculty of Medicine of the University of Geneva in the mid-1990s, several steps were taken to strengthen HP throughout the curriculum and include HP in its key domains as defined by the Ottawa Charter (OC).

Distinct roles of NFATc1 and NFATc4 in human primary myoblast differentiation and in the maintenance of reserve cells.

Ca signaling plays a key role during human myoblast differentiation. Among Ca-sensitive pathways, calcineurin is essential for myoblast differentiation and muscle regeneration. Nuclear factor of activated T-cell (NFAT) transcription factors are the major calcineurin targets.

TRPC1 and TRPC4 channels functionally interact with STIM1L to promote myogenesis and maintain fast repetitive Ca release in human myotubes.

STIM1 and Orai1 are essential players of store-operated Ca entry (SOCE) in human skeletal muscle cells and are required for adult muscle differentiation. Besides these two proteins, TRPC (transient receptor potential canonical) channels and STIM1L (a longer STIM1 isoform) are also present on muscle cells. In the present study, we assessed the role of TRPC1, TRPC4 and STIM1L in SOCE, in the maintenance of repetitive Ca transients and in muscle differentiation.

[International Health Electives in developing countries for medical and nursing students: four experiences from French-speaking Switzerland].

International Health Electives performed in developing countries by students of medical and nursing schools from industrialized nations have recently become a highly valued element in curricula of medical and nursing schools. We report here four examples of such electives developed over the years at the Faculties of medicine of Geneva and Lausanne, one involving both medical and nursing school students. These electives foster enthusiasm and commitment among students and host institutions abroad.

STIM1L traps and gates Orai1 channels without remodeling the cortical ER.

STIM proteins populate and expand cortical endoplasmic reticulum (ER) sheets to mediate store-operated Ca(2+) entry (SOCE) by trapping and gating Orai channels in ER-plasma membrane clusters. A longer splice variant, STIM1L, forms permanent ER-plasma membrane clusters and mediates rapid Ca(2+) influx in muscle. Here, we used electron microscopy, total internal reflection fluorescence (TIRF) microscopy and Ca(2+) imaging to establish the trafficking and signaling properties of the two STIM1 isoforms in Stim1(-/-)/Stim2(-/-) fibroblasts.

Inositol 1,4,5 trisphosphate receptor 1 is a key player of human myoblast differentiation.

Cytosolic Ca(2+) signals are fundamental for the early and late steps of myoblast differentiation and are, as in many cells, generated by Ca(2+) release from internal stores as well as by plasma membrane Ca(2+) entry. Our recent studies identified the store-operated Ca(2+) channels, Orai1 and TRPC1&C4, as crucial for the early steps of human myogenesis and for the late fusion events. In the present work, we assessed the role of the inositol-1,4,5 tris-phosphate receptor (IP3R) type 1 during human myoblast differentiation.

The predictive validity of the aptitude test for the performance of students starting a medical curriculum.

Introduction: Selection of medical students varies between German- and French-speaking Swiss faculties. Geneva introduced an aptitude test in 2010, aimed at helping decision making among students. The test was compulsory: it had to be taken by those who intended to register for medical studies.

During post-natal human myogenesis, normal myotube size requires TRPC1- and TRPC4-mediated Ca²⁺ entry.

Myogenesis involves expression of muscle-specific transcription factors such as myogenin and myocyte enhancer factor 2 (MEF2), and is essentially regulated by fluctuations of cytosolic Ca(2+) concentration. Recently we demonstrated that molecular players of store-operated Ca(2+) entry (SOCE), stromal interacting molecule (STIM) and Orai, were fundamental in the differentiation process of post-natal human myoblasts. Besides STIM and Orai proteins, the family of transient receptor potential canonical (TRPC) channels was shown to be part of SOCE in several cellular systems.

[Community immersion program at Geneva medical school: a fifteen-year experience].

Over the past decades there have been many new developments in medical education due to new public health challenges and to new learning theories. Medical schools throughout the world have adapted to these challenges in adopting community-based learning activities, an approach that the World Health Organization has promoted. The aim of the present article is to describe the characteristics, as well as the evolution, of such a community-based training program which has been implemented over 15 years at the Faculty of medicine of the University of Geneva and to present some evaluation data addressing students' perception, achievement of learning objectives as well as interactions between students and the community.

Design, implementation and evaluation of a community health training program in an integrated problem-based medical curriculum: a fifteen-year experience at the University of Geneva Faculty of Medicine.

Background: In the literature the need for relevance in medical education and training has been stressed. In the last 40 years medical schools have been challenged to train doctors competent to respond to community health needs. In the mid-90s the University of Geneva Faculty of Medicine introduced an integrated medical curriculum.

Sleep-deprivation regulates α-2 adrenergic responses of rat hypocretin/orexin neurons.

We recently demonstrated, in rat brain slices, that the usual excitation by noradrenaline (NA) of hypocretin/orexin (hcrt/orx) neurons was changed to an inhibition following sleep deprivation (SD). Here we describe that in control condition (CC), i.e.

Initiation of human myoblast differentiation via dephosphorylation of Kir2.1 K+ channels at tyrosine 242.

Myoblast differentiation is essential to skeletal muscle formation and repair. The earliest detectable event leading to human myoblast differentiation is an upregulation of Kir2.1 channel activity, which causes a negative shift (hyperpolarization) of the resting potential of myoblasts.

Myogenic precursor cell transplantation in pigs: a step towards a clinical use for muscle regeneration?

It is most probable that, in a near future, myogenic precursor cell transplants will have clinical applications in domains as different as orthopaedics, endocrinology, management of heart infarct, and therapies of muscle diseases. We have proposed to introduce the use of myogenic precursor cell transplantation in patients, after preliminary tests in a large animal model, the pig. Our initial effort was centred on the domain of orthopaedics.

The calcineurin pathway links hyperpolarization (Kir2.1)-induced Ca2+ signals to human myoblast differentiation and fusion.

In human myoblasts triggered to differentiate, a hyperpolarization, resulting from K+ channel (Kir2.1) activation, allows the generation of an intracellular Ca2+ signal. This signal induces an increase in expression/activity of two key transcription factors of the differentiation process, myogenin and MEF2.

Calcium sources used by post-natal human myoblasts during initial differentiation.

Increases in cytoplasmic Ca(2+) are crucial for inducing the initial steps of myoblast differentiation that ultimately lead to fusion; yet the mechanisms that produce this elevated Ca(2+) have not been fully resolved. For example, it is still unclear whether the increase comes exclusively from membrane Ca(2+) influx or also from Ca(2+) release from internal stores. To address this, we investigated early differentiation of myoblast clones each derived from single post-natal human satellite cells.

[How should a muscular disease be studied?].

Muscle diseases are an expanding field, mainly due to the progress in genetics and biochemistry. Evaluation starts with a thorough history of the patient's symptoms and signs. The leading clinical manifestations are weakness, atrophy, myalgia, fatigue, more rarely myotonia and in the child hypotonia or walking difficulty.

Membrane hyperpolarization triggers myogenin and myocyte enhancer factor-2 expression during human myoblast differentiation.

It is widely thought that myogenin is one of the earliest detectable markers of skeletal muscle differentiation. Here we show that, during human myoblast differentiation, an inward rectifier K(+) channel (Kir2.1) and its associated hyperpolarization trigger expression and activity of the myogenic transcription factors, myogenin and myocyte enhancer factor-2 (MEF2).

Non-hematopoietic human bone marrow contains long-lasting, pluripotential mesenchymal stem cells.

Mesenchymal stem cells (MSC) are considered as potential agents for reconstructive and gene-targeting therapies since they differentiate into various cell-lineages, exhibit an extended survival once injected into a host, and can easily be transfected with engineered DNA. MSC are essentially isolated from hematopoietic bone marrow (BM), a process that is rather invasive and may raise ethical concerns. In an attempt to find an alternative source, we evaluated whether non-hematopoietic (nh)BM recovered from femoral heads of patients undergoing hip arthroplasty contained MSC.

Lentivector-mediated transfer of Bmi-1 and telomerase in muscle satellite cells yields a duchenne myoblast cell line with long-term genotypic and phenotypic stability.

Conditionally immortalized human cells are valuable substrates for basic biologic studies, as well as for the production of specific proteins and for the creation of bioartificial organs. We previously demonstrated that the lentivector-mediated transduction of immortalizing genes into human primary cells is an efficient method for obtaining such cell lines. Here, we used human muscle satellite cells as model targets to examine the impact of the transduced genes on the genotypic and phenotypic characteristics of the immortalized cells.

Acceleration of human myoblast fusion by depolarization: graded Ca2+ signals involved.

We have previously shown that human myoblasts do not fuse when their voltage fails to reach the domain of a window T-type Ca(2+) current. We demonstrate, by changing the voltage in the window domain, that the Ca(2+) signal initiating fusion is not of the all-or-none type, but can be graded and is interpreted as such by the differentiation program. This was carried out by exploiting the properties of human ether-à-go-go related gene K(+) channels that we found to be expressed in human myoblasts.