Traumatic Childbirth and Birth-Related Post-Traumatic Stress Disorder in the Time of the COVID-19 Pandemic: A Prospective Cohort Study.

BACKGROUND: Birth-related post-traumatic stress disorder occurs in 4.7% of mothers. No previous study focusing precisely on the stress factors related to the COVID-19 pandemic regarding this important public mental health issue has been conducted. However, the stress load brought about by the COVID-19 pandemic could have influenced this risk. METHODS: We aimed to estimate the prevalence of traumatic childbirth and birth-related PTSD and to analyze the risk and protective factors involved, including the risk factors related to the COVID-19 pandemic. We conducted a prospective cohort study of women who delivered at the University Hospitals of Geneva between 25 January 2021 and 10 March 2022 with an assessment within 3 days of delivery and a clinical interview at one month post-partum. RESULTS: Among the 254 participants included, 35 (21.1%, 95% CI: 15.1-28.1%) experienced a traumatic childbirth and 15 (9.1%, 95% CI: 5.2-14.6%) developed a birth-related PTSD at one month post-partum according to DSM-5. Known risk factors of birth-related PTSD such as antenatal depression, previous traumatic events, neonatal complications, peritraumatic distress and peritraumatic dissociation were confirmed. Among the factors related to COVID-19, only limited access to prenatal care increased the risk of birth-related PTSD. CONCLUSIONS: This study highlights the challenges of early mental health screening during the maternity stay when seeking to provide an early intervention and reduce the risk of developing birth-related PTSD. We found a modest influence of stress factors directly related to the COVID-19 pandemic on this risk.

Simultaneous targeting of DNA replication and homologous recombination in glioblastoma with a polyether ionophore.

BACKGROUND: Despite significant endeavor having been applied to identify effective therapies to treat glioblastoma (GBM), survival outcomes remain intractable. The greatest nonsurgical benefit arises from radiotherapy, though tumors typically recur due to robust DNA repair. Patients could therefore benefit from therapies with the potential to prevent DNA repair and synergize with radiotherapy. In this work, we investigated the potential of salinomycin to enhance radiotherapy and further uncover novel dual functions of this ionophore to induce DNA damage and prevent repair. METHODS: In vitro primary GBM models and ex vivo GBM patient explants were used to determine the mechanism of action of salinomycin by immunoblot, flow cytometry, immunofluorescence, immunohistochemistry, and mass spectrometry. In vivo efficacy studies were performed using orthotopic GBM animal xenograft models. Salinomycin derivatives were synthesized to increase drug efficacy and explore structure-activity relationships. RESULTS: Here we report novel dual functions of salinomycin. Salinomycin induces toxic DNA lesions and prevents subsequent recovery by targeting homologous recombination (HR) repair. Salinomycin appears to target the more radioresistant GBM stem cell-like population and synergizes with radiotherapy to significantly delay tumor formation in vivo. We further developed salinomycin derivatives which display greater efficacy in vivo while retaining the same beneficial mechanisms of action. CONCLUSION: Our findings highlight the potential of salinomycin to induce DNA lesions and inhibit HR to greatly enhance the effect of radiotherapy. Importantly, first-generation salinomycin derivatives display greater efficacy and may pave the way for clinical testing of these agents.

Synthesis of spirocyclic orthoesters by 'anomalous' rhodium(ii)-catalysed intramolecular C-H insertions.

A tetrahydropyranyl acetal bearing a proximal phenyl diazoketone substituent underwent Rh(ii)-catalysed C-H insertion via an 'anomalous' C-O bond-forming, rather than C-C bond-forming, transformation, giving spirocyclic orthoesters. Density functional theory calculations with M06 show that the formation of these anomalous products involves hydride transfer to the rhodium carbene, giving an intermediate zwitterion which undergoes C-O bond formation in preference to C-C bond formation.

Rhodium(II)-catalysed intramolecular C-H insertion α- to oxygen: reactivity, selectivity and applications to natural product synthesis.

The selective functionalisation of C-H bonds is a powerful strategy for the construction of organic molecules and the Rh(II)-catalysed C-H insertion reaction is a particularly robust and useful tool for this purpose. This review discusses the insertion of Rh(II) carbenes into C-H bonds that are activated by α-oxygen substituents, focusing on the trends that have been observed in reactivity and selectivity, and the applications of this reaction to the total synthesis of complex natural products.

Severe hypothyroidism after contrast enema in premature infants.

Premature newborns are particularly vulnerable to iatrogenic hypothyroidism due to iodine exposure, usually through skin absorption of iodine-containing disinfectants or intravenous administration of iodinated contrast agents. We report here a case of severe iatrogenic hypothyroidism with goiter and cholestasis, discovered six weeks after a contrast enema using sodium ioxitalamate, an iodinated contrast agent. Prematurity, intrauterine growth retardation, and enteral feeding intolerance could explain why this complication occurred after contrast enema. Our observations suggest that indications of contrast enema in neonates need to be carefully considered, and when necessary, thyroid function should be monitored, especially in very premature infants.