[The feminization of precariousness, a growing feature]. / La féminisation de la précarité, une particularité grandissante.

Precariousness (social, health, professional, financial, energy, etc.) affects women more than men. This has consequences for their access to healthcare. Raising awareness of gender inequalities and mobilizing actors to fight against them, make visible the levers to fight against the increase of women's precariousness.

Whole-Body Metabolism and the Musculoskeletal Impacts of Targeting Activin A and Myostatin in Severe Osteogenesis Imperfecta.

Mutations in the COL1A1 and COL1A2 genes, which encode type I collagen, are present in around 85%-90% of osteogenesis imperfecta (OI) patients. Because type I collagen is the principal protein composition of bones, any changes in its gene sequences or synthesis can severely affect bone structure. As a result, skeletal deformity and bone frailty are defining characteristics of OI. Homozygous oim/oim mice are utilized as models of severe progressive type III OI. Bone adapts to external forces by altering its mass and architecture. Previous attempts to leverage the relationship between muscle and bone involved using a soluble activin receptor type IIB-mFc (sActRIIB-mFc) fusion protein to lower circulating concentrations of activin A and myostatin. These two proteins are part of the TGF-ß superfamily that regulate muscle and bone function. While this approach resulted in increased muscle masses and enhanced bone properties, adverse effects emerged due to ligand promiscuity, limiting clinical efficacy and obscuring the precise contributions of myostatin and activin A. In this study, we investigated the musculoskeletal and whole-body metabolism effect of treating 5-week-old wildtype (Wt) and oim/oim mice for 11 weeks with either control antibody (Ctrl-Ab) or monoclonal anti-activin A antibody (ActA-Ab), anti-myostatin antibody (Mstn-Ab), or a combination of ActA-Ab and Mstn-Ab (Combo). We demonstrated that ActA-Ab treatment minimally impacts muscle mass in oim/oim mice, whereas Mstn-Ab and Combo treatments substantially increased muscle mass and overall lean mass regardless of genotype and sex. Further, while no improvements in cortical bone microarchitecture were observed with all treatments, minimal improvements in trabecular bone microarchitecture were observed with the Combo treatment in oim/oim mice. Our findings suggest that individual or combinatorial inhibition of myostatin and activin A alone is insufficient to robustly improve femoral biomechanical and microarchitectural properties in severely affected OI mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Combinatorial Inhibition of Myostatin and Activin A Improves Femoral Bone Properties in the G610C Mouse Model of Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a collagen-related bone disorder characterized by fragile osteopenic bone and muscle weakness. We have previously shown that the soluble activin receptor type IIB decoy (sActRIIB) molecule increases muscle mass and improves bone strength in the mild to moderate G610C mouse model of OI. The sActRIIB molecule binds multiple transforming growth factor-ß (TGF-ß) ligands, including myostatin and activin A. Here, we investigate the musculoskeletal effects of inhibiting activin A alone, myostatin alone, or both myostatin and activin A in wild-type (Wt) and heterozygous G610C (+/G610C) mice using specific monoclonal antibodies. Male and female Wt and +/G610C mice were treated twice weekly with intraperitoneal injections of monoclonal control antibody (Ctrl-Ab, Regn1945), anti-activin A antibody (ActA-Ab, Regn2476), anti-myostatin antibody (Mstn-Ab, Regn647), or both ActA-Ab and Mstn-Ab (Combo, Regn2476, and Regn647) from 5 to 16 weeks of age. Prior to euthanasia, whole body composition, metabolism and muscle force generation assessments were performed. Post euthanasia, hindlimb muscles were evaluated for mass, and femurs were evaluated for changes in microarchitecture and biomechanical strength using micro-computed tomography (µCT) and three-point bend analyses. ActA-Ab treatment minimally impacted the +/G610C musculoskeleton, and was detrimental to bone strength in male +/G610C mice. Mstn-Ab treatment, as previously reported, resulted in substantial increases in hindlimb muscle weights and overall body weights in Wt and male +/G610C mice, but had minimal skeletal impact in +/G610C mice. Conversely, the Combo treatment outperformed ActA-Ab alone or Mstn-Ab alone, consistently increasing hindlimb muscle and body weights regardless of sex or genotype and improving bone microarchitecture and strength in both male and female +/G610C and Wt mice. Combinatorial inhibition of activin A and myostatin more potently increased muscle mass and bone microarchitecture and strength than either antibody alone, recapturing most of the observed benefits of sActRIIB treatment in +/G610C mice. © 2022 American Society for Bone and Mineral Research (ASBMR).

The relationship between residential proximity to extremely low frequency power transmission lines and adverse birth outcomes.

BACKGROUND: Occupational exposure to electromagnetic fields has been linked to adverse birth outcomes. This study evaluated whether maternal residential proximity to power transmission lines was associated with adverse birth outcomes. METHODS: Live singleton births in the Montréal and Québec census metropolitan areas from 1990 to 2004 were extracted from the Québec birth file (N=707,215). Proximity was defined as residing within 400 m of a transmission line. Generalised estimating equations were used to evaluate associations between residential proximity to transmission lines and preterm birth (PTB), low birth weight (LBW), small-for-gestational age (SGA) birth and infant sex, accounting for maternal age, education, marital status, ethnicity, parity, period of birth, and neighbourhood median household income. RESULTS: There was no association between residential proximity to transmission lines and PTB, LBW and infant sex in unadjusted and adjusted models. A lower likelihood of SGA birth was present for some distance categories (eg, adjusted OR 0.88, 95% CI 0.81 to 0.95 for 50-75 m relative to ≥400 m). CONCLUSION: Residential proximity to transmission lines is not associated with adverse births outcomes.