The impact of chemical pollution across major life transitions: a meta-analysis on oxidative stress in amphibians.

Among human actions threatening biodiversity, the release of anthropogenic chemical pollutants which have become ubiquitous in the environment, is a major concern. Chemical pollution can induce damage to macromolecules by causing the overproduction of reactive oxygen species, affecting the redox balance of animals. In species undergoing metamorphosis (i.e. the vast majority of the extant animal species), antioxidant responses to chemical pollution may differ between pre- and post-metamorphic stages. Here, we meta-analysed (N = 104 studies, k = 2283 estimates) the impact of chemical pollution on redox balance across the three major amphibian life stages (embryo, tadpole, adult). Before metamorphosis, embryos did not experience any redox change while tadpoles activate their antioxidant pathways and do not show increased oxidative damage from pollutants. Tadpoles may have evolved stronger defences against pollutants to reach post-metamorphic life stages. In contrast, post-metamorphic individuals show only weak antioxidant responses and marked oxidative damage in lipids. The type of pollutant (i.e. organic versus inorganic) has contrasting effects across amphibian life stages. Our findings show a divergent evolution of the redox balance in response to pollutants across life transitions of metamorphosing amphibians, most probably a consequence of differences in the ecological and developmental processes of each life stage.

Are patients with low body mass index candidates for deep inferior epigastric perforator flaps for unilateral breast reconstruction?

Thin women have not traditionally been considered ideal candidates for autologous breast reconstruction. The purpose of this study was to examine the use of deep inferior epigastric perforator (DIEP) flap reconstruction in thin women undergoing immediate unilateral breast reconstruction. A retrospective review of 1,040 consecutive patients was performed. In total, 381 patients met the inclusion criteria. To improve clinical interpretability, patients were divided into three groups based on body mass index: "thin" (BMI ≤ 22.99), "traditional" (>23 and ≤29.99), and "obese" (BMI >30) candidates. Flap characteristics were compared to mastectomy weights, and postoperative complications were analyzed. In all groups, flap size was generally more than sufficient to match the mastectomy specimen, as flap weight:mastectomy weight ratio ws greater than 1 in all groups with no significant difference between groups (1.1 in thin patients, 1.0 in traditional patients, and 1.0 in obese patients). Fat necrosis prevalence was lowest in the thin group (12.5%), compared to the traditional (15.9%, P = 0.443) or obese (14.4%, P = 0.698) groups. Prevalence of breast infection were lower in the thin patients (5.2%) versus the traditional (8.7%, P = 0.287) or obese (14.4%, P = 0.033). Abdominal wound healing complications and seroma were also lowest in thin patients. DIEP flap breast reconstruction may be an effective method for unilateral breast reconstruction in thin patients, with sufficient flap weights and lower incidence of complications than in heavier patients. As such, low BMI may not present a barrier in the reconstruction of a breast mound matching native breast size.

Co-targeting of convergent nucleotide biosynthetic pathways for leukemia eradication.

Pharmacological targeting of metabolic processes in cancer must overcome redundancy in biosynthetic pathways. Deoxycytidine (dC) triphosphate (dCTP) can be produced both by the de novo pathway (DNP) and by the nucleoside salvage pathway (NSP). However, the role of the NSP in dCTP production and DNA synthesis in cancer cells is currently not well understood. We show that acute lymphoblastic leukemia (ALL) cells avoid lethal replication stress after thymidine (dT)-induced inhibition of DNP dCTP synthesis by switching to NSP-mediated dCTP production. The metabolic switch in dCTP production triggered by DNP inhibition is accompanied by NSP up-regulation and can be prevented using DI-39, a new high-affinity small-molecule inhibitor of the NSP rate-limiting enzyme dC kinase (dCK). Positron emission tomography (PET) imaging was useful for following both the duration and degree of dCK inhibition by DI-39 treatment in vivo, thus providing a companion pharmacodynamic biomarker. Pharmacological co-targeting of the DNP with dT and the NSP with DI-39 was efficacious against ALL models in mice, without detectable host toxicity. These findings advance our understanding of nucleotide metabolism in leukemic cells, and identify dCTP biosynthesis as a potential new therapeutic target for metabolic interventions in ALL and possibly other hematological malignancies.