Cancer Patient Beliefs and Attitudes Regarding Immune Checkpoint Inhibitor Therapy

The development and widespread use of immune checkpoint inhibitors (ICIs) have advanced the field of oncology in a short period of time. Despite this, patient perception regarding this new medication class has not been adequately assessed, which may affect treatment decisions and adherence. The Belief about Medicines Questionnaire (BMQ) is a validated survey composed of 18 questions which analyzes patient’s beliefs about the necessity of prescribed medication and concern about the potential adverse events caused by the medication. General medication overuse and harm are also determined. This is the first study to utilize the BMQ for patients on ICI therapy

TRAITEMENT DES DYSKINESIES TARDIVES INDUITES PAR LES NEUROLEPTIQUES (USAGE DE LA TETRABENAZINE DANS UN SERVICE DE NEUROLOGIE (HOPITAL NEUROLOGIQUE DE LYON))

LYON1-BU Santé (693882101) / SudocSudocFranceF

Pax6-induced alteration of cell fate: shape changes, expression of neuronal alpha tubulin, postmitotic phenotype, and cell migration

The transcription factor Pax6 plays an important role in the development of the central nervous system. To understand its mechanism of action, we transduced HeLa cells with a Pax6-expressing lentiviral vector. Upon transduction, HeLa cells markedly changed shape and formed neuritelike extensions. Pax6-transduced HeLa cells expressed high levels of neuronal alpha3 tubulin, demonstrating a partial transdifferentiation towards a neuronal phenotype. Neurons are postmitotic cells. Pax6-transduced HeLa cells became postmitotic through mechanisms involving up-regulation of p53 and cyclin-dependent kinase inhibitor p21. One of the most striking effects of Pax6 was observed by time-lapse videomicroscopy: cells started to dissociate from cell clusters and displayed intense migratory activity. Migration was accompanied by dynamic and reversible shape changes. Our results identified three elements of Pax6 action: (i) expression of neuron-specific genes; (ii) establishment of a postmitotic phenotype; and (iii) involvement in the regulation of cell shape and cell migration

Induction of enhanced green fluorescent protein expression in response to lesions in the nervous system

We have generated a mouse strain carrying a transgene driven by a strong and ubiquitous promoter (human cytomegalovirus hCMV/beta-actin) and containing an enhanced green fluorescent protein (eGFP) coding sequence upstream of the 3' untranslated region (3'UTR) of tissue-type plasminogen activator (t-PA) mRNA. The 3'UTR of t-PA mRNA is known to be involved in the reversible deadenylation and translational repression of transcripts in mouse oocytes. hCMV/beta-actin-eGFP-3'UTR t-PA transgenic mice express eGFP mRNA in all brain structures analyzed but lack eGFP fluorescence, with the exception of blood vessels, choroid plexus, and Purkinje cells. Taking advantage of these features, we tested whether certain pathological conditions, in particular injuries of the nervous system, might trigger eGFP fluorescence in traumatized cells or neurons. From this perspective, we analyzed eGFP mRNA expression and eGFP fluorescence in experimental models of nervous system lesions, such as motoneuron axotomy and cerebral stroke induced by middle cerebral artery occlusion. We found an increase in eGFP fluorescence in specific brain areas in cells suffering or reacting to these injuries. This increased fluorescence is correlated with an increased transcription of eGFP in lesioned cells, presumably enhanced by a release of the translational silencing mediated by the 3'UTR region of the t-PA mRNA. This transgenic mouse model may prove useful to study the development of neurodegenerative lesions

ACTIFPARK, programme d’éducation thérapeutique à l’activité physique adaptée à un stade débutant de la maladie de Parkinson : résultats préliminaires chez 16 patients

International audienceIntroductionUne activité physique régulière est recommandée au cours de la maladie de Parkinson. Elle nécessite une modification des habitudes de vie qui peut être facilitée par l’éducation thérapeutique.ObjectifsÉvaluer la faisabilité et l’impact d’une éducation à l’activité physique sur la stabilité posturale, d’endurance cardio-vasculaire et d’activité physique quotidienne chez des patients débutant la maladie de Parkinson.Patients et méthodesLe programme ACTIFPARK s’adresse à des patients dont le diagnostic remonte à moins de 3 ans et comprend une visite d’évaluation (actimétrie sur 7jours, épreuve d’effort sous-maximale, évaluation sur plateforme de posturographie), 3 séances éducatives collectives (théorie et pratique) réalisées sur 3 semaines, portant sur la réadaptation à l’effort, le travail de l’équilibre et le renforcement musculaire, et une séance de consolidation à 3 mois. L’évaluation est répétée 3 mois après la dernière séance.RésultatsSeize patients ont participé au programme entre septembre 2017 et juin 2018. Suite à la participation, le temps passé en activité physique modérée à intense a augmenté (25,6±18,7 vs 30±18,1min/j, p<0,05). Lors de l’épreuve d’effort, la fréquence cardiaque était plus basse pour les paliers de 50W, 90W et 110W. La stabilité posturale était améliorée (functional reach test : 26,7±5,8 vs 30,3±7,4cm, p<0,05).DiscussionCette étude préliminaire permet de démontrer la faisabilité et l’intérêt d’un programme court d’éducation à l’activité physique incluant une pratique en groupe chez des patients parkinsoniens à un stade débutant de la maladie. Si les résultats sont satisfaisants, l’absence de groupe contrôle ne permet pas de conclure définitivement en termes d’efficacité et incite à proposer une étude prospective contrôlée randomisée.ConclusionL’éducation thérapeutique à l’activité physique au stade débutant de la maladie de Parkinson semble efficace pour entraîner une modification des habitudes de vie 3 mois après la fin du programme

Gene expression during sex determination reveals a robust female genetic program at the onset of ovarian development

The primary event in mammalian sexual development is the differentiation of the bipotential gonads into either testes or ovaries. Our understanding of the molecular pathways specifying gonadal differentiation is still incomplete. To identify the initial molecular changes accompanying gonadal differentiation in mice, we have performed a large-scale transcriptional analysis of XX and XY Sf1-positive gonadal cells during sex determination. In both male and female genital ridges, a robust genetic program is initiated pre-dating the first morphological changes of the differentiating gonads. Between E10.5 and E13.5, 2306 genes were expressed in a sex-specific manner in the somatic compartment of the gonads; 1223 were overexpressed in XX embryos and 1083 in XY embryos. Although sexually dimorphic genes were scattered throughout the mouse genome, we identified chromosomal regions hosting clusters of genes displaying similar expression profiles. The cyclin-dependent kinase inhibitors Cdkn1a and Cdkn1c are overexpressed in XX gonads at E11.5 and E12.5, suggesting that the increased proliferation of XY gonads relative to XX gonads may result from the overexpression of cell cycle inhibitors in the developing ovaries. These studies define the major characteristics of testicular and ovarian transcriptional programs and reveal the richness of signaling processes in differentiation of the bipotential gonads into testes and ovaries