Mol-CycleGAN: a generative model for molecular optimization

Designing a molecule with desired properties is one of the biggest challenges in drug development, as it requires optimization of chemical compound structures with respect to many complex properties. To improve the compound design process, we introduce Mol-CycleGAN—a CycleGAN-based model that generates optimized compounds with high structural similarity to the original ones. Namely, given a molecule our model generates a structurally similar one with an optimized value of the considered property. We evaluate the performance of the model on selected optimization objectives related to structural properties (presence of halogen groups, number of aromatic rings) and to a physicochemical property (penalized logP). In the task of optimization of penalized logP of drug-like molecules our model significantly outperforms previous results

Prognostic value of renal fractional flow reserve in blood pressure response after renal artery stenting (PREFER study)

Background: The aim of our study was to determine a potential relationship between restingtranslesional pressures ratio (Pd/Pa ratio), renal fractional fl ow reserve (rFFR) and bloodpressure response after renal artery stenting.Methods: Thirty fi ve hypertensive patients (49% males, mean age 64 years) with at least60% stenosis in angiography, underwent renal artery stenting. Translesional systolic pressuregradient (TSPG), Pd/Pa ratio (the ratio of mean distal to lesion and mean proximal pressures)and hyperemic rFFR — after intrarenal administration of papaverine — were measured beforestent implantation. Ambulatory blood pressure measurements (ABPM) were recorded beforethe procedure and after 6 months. The ABPM results were presented as blood pressure changesin subgroups of patients with normal (≥ 0.9) vs. abnormal (< 0.9) Pd/Pa ratio and normal(≥ 0.8) vs. abnormal (< 0.8) rFFR.Results: Median Pd/Pa ratio was 0.84 (interquartile range 0.79–0.91) and strongly correlatedwith TSPG (r = –0.89, p < 0.001), minimal lumen diameter (MLD; r = 0.53, p < 0.005)and diameter stenosis (DS; r = –0.51, p < 0.005). Median rFFR was 0.78 (0.72–0.82). Similarly,signifi cant correlation between rFFR and TSPG (r = –0.86, p < 0.0001), as well as withMLD (r = 0.50, p < 0.005) and DS (r = –0.51, p < 0.005) was observed. Procedural successwas obtained in all patients. Baseline Pd/Pa ratio and rFFR did not predict hypertension responseafter renal artery stenting. Median changes of 24-h systolic/diastolic blood pressure werecomparable in patients with abnormal vs. normal Pd/Pa ratio (–4/–3 vs. 0/2 mm Hg; p = NS)and with abnormal vs. normal rFFR (–2/–1 vs. –2/–0.5 mm Hg, respectively).Conclusions: Physiological assessment of renal artery stenosis using Pd/Pa ratio and papaverine-induced renal fractional fl ow reserve did not predict hypertension response after renalartery stenting

Metronidazole-Induced Encephalopathy in a 16-Year-Old Girl with Crohn’s Disease: Case Report and Review of the Pediatric Literature

Metronidazole-induced encephalopathy (MIE) is a rare and unpredictable complication that is most commonly reported in adults. Here, we present the case of MIE in a patient treated with rectal, oral, and intravenous metronidazole. This is the first case of MIE reported after suppositories. A 16-year-old girl with Crohn’s disease treated with mesalazine and exclusive enteral nutrition was operated on due to perianal fistulas and abscesses. She received oral metronidazole for 25 days and rectal metronidazole for 15 days as an adjuvant before surgery. Moreover, 2.5 g of intravenous metronidazole was administrated during the perioperative period. The second day after the surgery, symptoms of cerebellar syndrome appeared. She presented with an inability to coordinate balance and gait. Although she showed accurate verbal responses, her speech was slow, slurred, and scanning. The finger–nose test was positive. The T2-weighted magnetic resonance imaging revealed an increased symmetrical signal within the dentate nuclei of the cerebellum and in the corpus callosum. The changes were characterized by restricted diffusion. Based on the clinical picture and magnetic resonance imaging findings, MIE was diagnosed. Treatment with metronidazole was discontinued. The cumulative dose of metronidazole that she received for 29 days was 54 g: 38 g p.o., 13.5 g p.r., and 2.5 g i,v. The first symptoms appeared on the 28th day of antibiotic therapy after receiving 52 g of metronidazole. The neurological symptoms resolved after six days; however, three days after the resolution, paresthesia appeared in the distal phalanges of both feet and lasted for approximately two months. Our report highlights that neurologic symptoms related to metronidazole treatment should raise the suspicion of MIE