19-fold higher, respectively, than in healthy children when treated with the same dose of 50 mg/kg. Pharmacodynamic verification indicated that the recommended doses of 28, 15, and 8 mg/kg administered three times daily (every 8 h) to pediatric patients with moderate, severe, and end-stage renal disease, respectively, were sufficient to attain the target of maintaining the free plasma concentration at or above minimum inhibitory concentration (MIC) during 70% of the dosing interval (70% fT > MIC nearly 100% target attainment for susceptible MIC of 4 mg/L and >70% for intermediate MIC of 8 mg/L). Our PBPK model can be an effective tool to support dosing recommendations in pediatric patients with different degrees of renal impairment.Neonatal hypoxic-ischemic encephalopathy (NHIE) is one of the most prevalent causes of death during the perinatal period. The lack of exposure to oxytocin is associated with NHIE-mediated severe brain injury. However, the underlying mechanism is not fully understood. This study combined immunohistochemistry with electrophysiological recordings of hippocampal CA1 neurons to investigate the role of oxytocin in an in vitro model of hypoxic-ischemic (HI) injury (oxygen and glucose deprivation, OGD) in postnatal day 7-10 rats. Immunohistochemical analysis showed that oxytocin largely reduced the relative intensity of TOPRO-3 staining following OGD in the hippocampal CA1 region.  https://www.selleckchem.com/products/g150.html  Whole-cell patch-clamp recording revealed that the OGD-induced onset time of anoxic depolarization (AD) was significantly delayed by oxytocin. This protective effect of oxytocin was blocked by pretreatment with [d(CH2)51, Tyr (Me)2, Thr4, Orn8, des-Gly-NH29] vasotocin (dVOT, an oxytocin receptor antagonist) or bicuculline (a GABAA receptor antagonist). Interestingly, oxytocin enhanced inhibitory postsynaptic currents in CA1 pyramidal neurons, which were abolished by tetrodotoxin or dVOT. In contrast, oxytocin had no effect on excitatory postsynaptic currents but induced an inward current in 86% of the pyramidal neurons tested. Taken together, these results demonstrate that oxytocin receptor signaling plays a critical role in attenuating neonatal neural death by facilitating GABAergic transmission, which may help to regulate the excitatory-inhibitory balance in local neuronal networks in NHIE patients.
  To evaluate the clinical outcomes of Descemet membrane endothelial keratoplasty (DMEK) for treating eyes with iridocorneal endothelial (ICE) syndrome and comparing the outcomes with those achieved after treating Fuchs endothelial dystrophy (FED).
 
  Prospective interventional comparative case series.
 
  Sixty-three patients (68 eyes) with ICE syndrome or FED were enrolled at the Zhongshan Ophthalmic Center between March 10, 2014 and May 11, 2018. Eligible patients were divided into 2 groups ICE group (eyes, 24; patients, 24) and FED group (eyes, 44; patients, 39). DMEK was performed in all cases. Corrected distance visual acuity (CDVA), endothelial cell loss (ECL), intraocular pressure (IOP), graft survival, and surgical complications were documented.
 
  In the ICE and FED groups, the mean follow-up duration was 24.9 ± 5 months and 25.2 ± 7.7 months, respectively. At 1 year postoperatively, Kaplan-Meier survival analysis demonstrated 85.7% and 100% cumulative graft success rates (P=.017) in patients with ICE and FED, respectively. Postoperative CDVA level was comparable between the 2 groups through 12-month follow-up; thereafter CDVA was better in the FED group than in the ICE group (P < .001). Moreover, postoperative ECL was significantly higher in the ICE group than in the FED group throughout the follow-up period (P < .001). A discernable increase in structural abnormalities of the anterior chamber angle was observed in 2 eyes (8.3%) in the ICE group; however, no significant differences were observed in the incidence of principal complications between the 2 groups.
 
  DMEK provides comparable short-term visual outcomes in the treatment of ICE to those observed in the treatment of FED, with higher postoperative ECL over FED.
 DMEK provides comparable short-term visual outcomes in the treatment of ICE to those observed in the treatment of FED, with higher postoperative ECL over FED.
  To develop a nomogram to predict the 3- and 5-year likelihood of graft survival after penetrating keratoplasty (PK) based on preoperative assessment and intraoperative plan.
 
  Retrospective clinical case-control study.
 
  Data from 1,029 consecutive PKs in 903 eyes of 835 patients performed at a single tertiary center from May 2007 to September 2018 were extracted from electronic medical records and evaluated for corneal graft failure, defined as irreversible and visually significant graft edema, haze, or scarring. Thirty-seven variables were assessed by multivariable Cox models. A nomogram to predict the probability of graft survival was created.
 
  Mean recipient age was 57.1 ± 22.0 years and mean follow-up was 4.22 ± 3.05 years. Overall, 37.4% of grafts failed during follow-up. Eleven variables were significantly associated with graft failure, including active microbial infection at the time of PK (hazard ratio [HR]=5.10, 95% confidence interval [CI] 3.53-7.37), intraocular silicone oil at the conclusion of the PK (HR=4.28, 95% CI 2.38-7.71), history of systemic autoimmune disease (HR=2.83, 95% CI 1.63-4.90), 4 quadrants of corneal neovascularization (HR=2.76, 95% CI 1.56-4.86), any prior anterior segment surgery (HR=2.41, 95% CI 1.55-3.75), and lens status as anterior chamber intraocular lens at the conclusion of surgery (HR=2.35, 95% CI 1.30-4.26). The nomogram exhibited a concordance index of 0.76 (95% CI 0.74-0.78); internal calibration plots depicted strong correlation between prediction and observation of graft survival.
 
  PK graft prognosis may be predicted relatively accurately based on 11 variables. Although established from retrospective data, this nomogram would be valuable for data-driven patient counseling prior to corneal transplantation.
 PK graft prognosis may be predicted relatively accurately based on 11 variables. Although established from retrospective data, this nomogram would be valuable for data-driven patient counseling prior to corneal transplantation.