M S-medecine Sciences最新文献

High-throughput sequencing has introduced the concept of "actionable genes". These genes are linked to diseases for which specific treatments or care exist. Accurate genetic diagnosis is therefore crucial for initiating interventions that can prevent or delay the progression of rare diseases. High-throughput sequencing has considerably increased the capacities of genetic analyses, but it has also led to an increase in requests for analyses, lengthening the time taken to obtain results. It is becoming necessary to prioritize analyses, especially when "actionable genes" are suspected to be implicated. In the case of myopathies, a French national study has identified 63 actionable genes, implicated in diseases for which a targeted treatment and/or priority care can be initiated, thereby improving the patient's prognosis. Despite advances, many rare diseases remain without specific treatments, underlining the continuing importance of research and innovation in medical genetics.

Duchenne muscular dystrophy (DMD) is a severe degenerative genetic muscle disease affecting mainly young boys, characterized by a significant alteration or absence of dystrophin expression. Significant strides have been made in comprehending and treating DMD, particularly with the recent approval of the first gene therapy using a recombinant adeno-associated vector (rAAV) to deliver a shortened form of dystrophin (microdystrophin). Nevertheless, major challenges remain in improving therapeutic outcomes. The use of rAAV vectors is hindered by major limitations, notably the risks of immunotoxicity and hepatotoxicity, linked to high-dose administration. Additionally, microdystrophin exhibits inherent functional limitations and immunological risks. This article examines these challenges and explores the avenues for enhancing gene therapy for DMD.

Smallpox was an endemic, very contagious disease which caused a high mortality rate during the age of enlightenment. In order to counter act this epidemic, smallpox inoculation was developed. This technique consisted in the inoculation of infected pus taken from a sick person into a healthy one in order to prevent the risks of natural smallpox infection. It was in this context that a German doctor in charge of inoculation wrote to Kant twice in 1799, and again in 1800, to ask him if inoculation was morally permissible. Kant wrote a draft of an answer, but it was never completed or published during his lifetime. These drafts provide elements of an answer that he nevertheless refused to give explicitly in the Doctrine of Virtue (1797) where the question of the morality of inoculation remained unanswered.

After years of studying cardiovascular diseases (CVD) in men due to their higher incidence compared to women, attention is now being paid to female CVD and their pathophysiology. Even though premenopausal women have a lower incidence of CVD, this disparity progressively diminishes after menopause, highlighting the key role of sex hormones. Many preclinical and fundamental studies have demonstrated protective effects of estrogens on arterial endothelium, suggesting that hormone therapy could improve cardiovascular health in menopausal women. However, disappointing outcomes from a major clinical trial two decades ago questioned the cardiovascular protection by estrogens with age. In this review, we will summarize the main clinical and experimental studies reporting the effects of estrogens on CVD, with a focus on their impact on endothelial function. Then, we will present abnormalities in the expression and signaling of estrogen receptors (ERs) in the arteries, and the contribution of conventional estrogens to arterial protection during aging. Finally, we will examine how recent advances in the mechanisms of action of ERa could help to optimize hormone therapy for menopause.

The deleterious effects of human activities on biodiversity in the vegetal and animal world, and on climate changes are now well-established facts. However, little is yet known on the impact of human activities on microbial diversity on the planet and more specifically on the human microbiota Large implementation of metagenomics allows exaustive microbial cataloguing with broad spatio-temporal resolution of human microbiota. A reduction in bacterial richness and diversity in the human microbiota, particularly in the intestinal tract, is now established and particularly obvious in the most industrialized regions of the planet. Massive, uncontrolled use of antibiotics, drastic changes in traditional food habits and some elements of the "global exposome" that remain to identify are usually considered as stressors accounting for this situation of "missing microbes". As a consequence, a dysbiotic situation develops, a "dysbiosis" being characterized by the erosion of the central core of shared bacterial species across individuals and the development of opportunistic "pathobionts" in response to a weaker barrier capacity of these impoverished microbiota. The current challenge is to establish a causality link between the extension of these dysbiotic situations and the steady emergence of epidemic, non-communicable diseases such as asthma, allergy, obesity, diabetes, autoimmune diseases and some cancers. Experimental animal models combined with controlled, prospective clinical interventions are in demand to consolidate causality links, with the understanding that in the deciphering of the mechanisms of alteration of the human-microbiome symbiosis resides a novel exciting chapter of medicine: "microbial medicine".

Multi-Cancer Early Detection is a highly popular topic, bringing the hope of being able to detect very early, non-symptomatic cancers and allowing more successful therapy. A major company in this space is GRAIL, which has attracted very significant financing and launched large-scale tests of its detection systems. However, the real clinical utility of these tests remains to be demonstrated, and fundamental issues are still pending.