Chronic toxicity of double-walled carbon nanotubes to three marine organisms: influence of different dispersion methods

Double-walled carbon nanotubes (DWNTs) are found in a variety of consumer products, but there are no ecotoxicity data of DWNTs into marine organisms. Materials & methods: Chronic toxicity of DWNTs was investigated with the diatom Thalassiosira pseudonana, copepod Tigriopus japonicus and medaka Oryzias melastigma. DWNTs were dispersed using sonication (so-DWNTs) and stirring (st-DWNTs) for comparison. Results: The median aggregation size (0.89 μm2) of so-DWNTs was smaller than that of st-DWNTs (21.8 μm2). Exposure to DWNTs led to growth inhibition of T. pseudonana with EC50s of 1.86 and 22.7 mg/l for so- and st-DWNTs, respectively. Population growth of T. japonicus was reduced to 0.1 mg/l for so-DWNTs and 10 mg/l for st-DWNTs. Growth inhibition in O. melastigma was observed at 10 mg/l for so-DWNTs but not for st-DWNTs. Conclusion:Given that so-DWNTs are consistently significantly more toxic than st-DWNTs, dispersion method and size of aggregations should be considered in DWNT toxicity testing

Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia

Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia. We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B cell-precursor acute lymphoblastic leukemia (ALL). Whole-exome sequencing identified a heterozygous single-nucleotide change in ETV6 (ets variant 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotypes identified 2 with ETV6 mutations. One family also had a mutation encoding p.Pro214Leu and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA-binding domain, with alternative splicing and exon skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AimThe SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery.MethodsThis was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin.ResultsOverall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P ConclusionOne in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease