[Colorectal cancer screening program in the canton of Vaud: raising awareness]. / Programme vaudois de dépistage du cancer colorectal : évolution de la sensibilisation.

After five years of deployment, the participation rate in the Vaud colorectal cancer (CRC) screening program remains below projected targets. It was found that the communication tools made available to the population did not provide explicit recommendations regarding how to participate. To this end, Unisanté led a project between 2022 and 2023 to increase awareness and widely disseminate tools specifically designed with the target population. The intention was to provide decision-support tools (I decide to participate) and guidance in the system (in what way) to improve participation by the population targeted by the Vaud CRC screening program. This project incorporated the principles of proportionate universalism, that is to say, adapting screening methods to the specific needs of population sub-groups, such as those in a disadvantaged socio-economic position with low or very low levels of health literacy.

À l'issue de cinq années de déploiement, le taux de participation de la population au programme vaudois de dépistage du cancer colorectal (CCR) s'est révélé en dessous des objectifs souhaités Afin de faciliter une décision de participation, un projet global a été conçu par Unisanté entre 2022 et 2023, dont la finalité était de déployer des actions spécifiques de sensibilisation et de mettre à disposition de la population cible des informations d'une très large accessibilité. L'intention était de disposer d'outils d'aide à la décision (je décide à participer) et d'orientation dans le dispositif (de quelle manière) permettant d'amplifier la participation de la population ciblée par le programme vaudois de dépistage du CCR. Ce projet a permis d'adapter la sensibilisation sur les modalités de dépistage aux populations avec un niveau de littératie en santé faible, voire très faible.

[Therapeutic advances in monoclonal gammopathy-associated renal diseases]. / Avancées thérapeutiques dans les maladies rénales associéesaux gammapathies monoclonales.

During the last ten years, significant advances have been made in the field of monoclonal gammopathy-associated renal diseases. These have consisted in a better recognition of their pathological and clinical significations and correlation. Furthermore, therapeutic advances have allowed improving the prognosis of B-cell monoclonal proliferations and of the related renal complications. In the peculiar case of the multiple myeloma with severe renal failure requiring dialysis, one can now expect better survival and chance of recovering renal function.

Au cours des dix dernières années, la prise en charge des maladies rénales associées aux gammapathies monoclonales a connu d'importants progrès. Ceux-ci ont consisté en une caractérisation pathologique plus précise des lésions rénales et une meilleure compréhension de leur signification clinique. En parallèle, les progrès thérapeutiques des proliférations monoclonales de la cellule B ont permis d'améliorer le pronostic de celles-ci et des atteintes rénales associées. Dans le cas particulier du myélome multiple, les patients souffrant d'insuffisance rénale sévère peuvent aujourd'hui bénéficier, avec peu de restrictions, de plusieurs nouveaux traitements efficaces. Cela autorise de meilleurs espoirs de survie et de récupération de la fonction rénale.

Trypsin cleaves acid-sensing ion channel 1a in a domain that is critical for channel gating.

Acid-sensing ion channels (ASICs) are neuronal Na(+) channels that are members of the epithelial Na(+) channel/degenerin family and are transiently activated by extracellular acidification. ASICs in the central nervous system have a modulatory role in synaptic transmission and are involved in cell injury induced by acidosis. We have recently demonstrated that ASIC function is regulated by serine proteases. We provide here evidence that this regulation of ASIC function is tightly linked to channel cleavage. Trypsin cleaves ASIC1a with a similar time course as it changes ASIC1a function, whereas ASIC1b, whose function is not modified by trypsin, is not cleaved. Trypsin cleaves ASIC1a at Arg-145, in the N-terminal part of the extracellular loop, between a highly conserved sequence and a sequence that is critical for ASIC1a inhibition by the venom of the tarantula Psalmopoeus cambridgei. This channel domain controls the inactivation kinetics and co-determines the pH dependence of ASIC gating. It undergoes a conformational change during inactivation, which renders the cleavage site inaccessible to trypsin in inactivated channels.

Selective regulation of acid-sensing ion channel 1 by serine proteases.

Acid-sensing ion channels (ASICs) are neuronal Na(+) channels that belong to the epithelial Na(+) channel/degenerin family. ASICs are transiently activated by a rapid drop in extracellular pH. Conditions of low extracellular pH, such as ischemia and inflammation in which ASICs are thought to be active, are accompanied by increased protease activity. We show here that serine proteases modulate the function of ASIC1a and ASIC1b but not of ASIC2a and ASIC3. We show that protease exposure shifts the pH dependence of ASIC1a activation and steady-state inactivation to more acidic pH. As a consequence, protease exposure leads to a decrease in current response if ASIC1a is activated by a pH drop from pH 7.4. If, however, acidification occurs from a basal pH of approximately 7, protease-exposed ASIC1a shows higher activity than untreated ASIC1a. We provide evidence that this bi-directional regulation of ASIC1a function also occurs in neurons. Thus, we have identified a mechanism that modulates ASIC function and may allow ASIC1a to adapt its gating to situations of persistent extracellular acidification.