Post-treatment alterations in white matter integrity in PTSD: Effects on symptoms and functional connectivity a secondary analysis of an RCT.

Post-traumatic stress disorder (PTSD) has been linked to altered communication within the limbic system, including reduced structural connectivity in the uncinate fasciculus (UNC; i.e., decreased fractional anisotropy; FA) and reduced resting-state functional connectivity (RSFC) between the hippocampus and ventromedial prefrontal cortex (vmPFC). Previous research has demonstrated attenuation of PTSD symptoms and alterations in RSFC following exposure-based psychotherapy. However, the relationship between changes in structural and functional connectivity patterns and PTSD symptoms following treatment remains unclear. To investigate this, we conducted a secondary analysis of data from a randomized clinical trial of intensive exposure therapy, evaluating alterations in UNC FA, hippocampus-vmPFC RSFC, and PTSD symptoms before (pre-treatment), 7 days after (post-treatment), and 30 days after (follow-up) the completion of therapy. Our results showed that post-treatment changes in RSFC were positively correlated with post-treatment and follow-up changes in UNC FA and that post-treatment changes in UNC FA were positively correlated with post-treatment and follow-up changes in PTSD symptoms. These findings suggest that early changes in functional connectivity are associated with sustained changes in anatomical connectivity, which in turn are linked to reduced PTSD symptom severity.

Process Intensification of the Continuous Synthesis of Bio-Derived Monomers for Sustainable Coatings Using a Taylor Vortex Flow Reactor.

We describe the optimization and scale-up of two consecutive reaction steps in the synthesis of bio-derived alkoxybutenolide monomers that have been reported as potential replacements for acrylate-based coatings (Sci. Adv.2020, 6, eabe0026). These monomers are synthesized by (i) oxidation of furfural with photogenerated singlet oxygen followed by (ii) thermal condensation of the desired 5-hydroxyfuranone intermediate product with an alcohol, a step which until now has involved a lengthy batch reaction. The two steps have been successfully telescoped into a single kilogram-scale process without any need to isolate the 5-hydroxyfuranone between the steps. Our process development involved FTIR reaction monitoring, FTIR data analysis via 2D visualization, and two different photoreactors: (i) a semicontinuous photoreactor based on a modified rotary evaporator, where FTIR and 2D correlation spectroscopy (2D-COS) revealed the loss of the methyl formate coproduct, and (ii) our fully continuous Taylor Vortex photoreactor, which enhanced the mass transfer and permitted the use of near-stoichiometric equivalents of O2. The use of in-line FTIR monitoring and modeling greatly accelerated process optimization in the Vortex reactor. This led to scale-up of the photo-oxidation in 85% yield with a projected productivity of 1.3 kg day-1 and a space-time yield of 0.06 mol day-1 mL-1. Higher productivities could be achieved while sacrificing yield (e.g., 4 kg day-1 at 40% yield). The use of superheated methanol at 200 °C in a pressurized thermal flow reactor accelerated the second step, the thermal condensation of 5-hydroxyfuranone, from a 20 h batch reflux reaction (0.5 L, 85 g) to a space time of <1 min in a reactor only 3 mL in volume operating with projected productivities of >700 g day-1. Proof of concept for telescoping the two steps was established with an overall two-step yield of 67%, producing a process with a projected productivity of 1.1 kg day-1 for the methoxybutenolide monomer without any purification of the 5-hydroxyfuranone intermediate.