Multi-omic lineage tracing predicts the transcriptional, epigenetic and genetic determinants of cancer evolution.

Cancer is a highly heterogeneous disease, where phenotypically distinct subpopulations coexist and can be primed to different fates. Both genetic and epigenetic factors may drive cancer evolution, however little is known about whether and how such a process is pre-encoded in cancer clones. Using single-cell multi-omic lineage tracing and phenotypic assays, we investigate the predictive features of either tumour initiation or drug tolerance within the same cancer population. Clones primed to tumour initiation in vivo display two distinct transcriptional states at baseline. Remarkably, these states share a distinctive DNA accessibility profile, highlighting an epigenetic basis for tumour initiation. The drug tolerant niche is also largely pre-encoded, but only partially overlaps the tumour-initiating one and evolves following two genetically and transcriptionally distinct trajectories. Our study highlights coexisting genetic, epigenetic and transcriptional determinants of cancer evolution, unravelling the molecular complexity of pre-encoded tumour phenotypes.

[Amniotic fluid analysis as a screening test in term and post-term pregnancy]. / La valutazione del liquido amniotico come test di screening nella gravidanza a termine ed oltre il termine.

BACKGROUND: To verify the hypothesis that isolated oligohydramnios in low-risk term or post-term pregnancy does not increase the risk of trauma to the fetus compared with a control group. METHODS: This prospective study compared a group of patients with low-risk pregnancy and oligohydramnios (AFI = or <50) and a control group which on ultrasonography performed 24 hours before delivery had an AFI volume >50 and = or <250 mm. The evaluation criteria included incidence of induction, modality of delivery and neonatal outcome. Statistical analysis was carried out using Student's "t"-test and the data set of categories was compared using the chi square test. RESULTS: From January 1997 to April 1999, 105 cases of oligohydramnios were compared with a control group (105 patients) matched for maternal age, gestation period and parity. The incidence of induction, fetal distress and variable deceleration was significantly higher in the group with AFI = or <50. The incidence of vacuum extractor, cesarean section, duration of labor and late deceleration did not differ between the two groups. No significant differences in neonatal outcome were found between the two groups. CONCLUSIONS: In patients with oligohydramnios without risk factors, the modality of delivery and neonatal outcome do not differ compared with those with normal amniotic fluid volume.

Antimicrobial prophylaxis in obstetric and gynecological surgery.

A major problem in obstetric and gynecological surgery, especially following cesarean section in labor, total vaginal or abdominal hysterectomy, or myomectomy, is postoperative wound infection. Consequently, the use of antimicrobial prophylaxis for cesarean section and for gynecological surgery has been advocated and shown to be effective in reducing postoperative morbidity, costs and duration of hospitalization. We reviewed 1021 patients who underwent cesarean section (597 elective, 424 emergency) and 814 gynecological patients undergoing abdominal (373) or vaginal (248) hysterectomy and myomectomy (193) between 1997-98 in the Obstetrics and Gynecology Clinic of the University of Florence. Before surgery 83.6% of obstetric and 75.1% of gynecological patients received 1 or 2 g of a first or second generation cephalosporin i.v. as a single-dose regimen at induction of anesthesia and sometimes a second postoperative dose. 1.5% of obstetric surgical patients had wound infection, as did 2.8% of gynecological surgery patients, with a mean postoperative hospital stay of 8 days. The short-term perioperative antimicrobial prophylaxis with cephalosporins is useful and provides the benefit of minimal toxicity and risk of chemoresistance.