Characterization of NP22 and its Potential Role in NMDA Receptor-mediated Transmission

N-methyl D-aspartate (NMDA) receptors represent integral signal transducers for excitatory glutamate neurotransmission. While NMDA receptors are critical for synaptic plasticity, the molecular events underlying this process are not fully elucidated. The potential role of NP22, a novel neuronal protein, as a downstream mediator of NMDA receptor function is explored. NP22 protein expression in genetic and pharmacological models of NMDA receptor hypofunction is examined and no significant changes are reported. Characterization of the NP22 protein complex via tandem-affinity and FLAG-purification coupled with mass spectrometry was used and no novel protein interactions are reported. GFP-tagged NP22 colocalization with F-actin decreases in cell processes of transiently transfected HEK293 cells in response to elevated intracellular calcium, while similar colocalization reductions are not seen in stably transfected HEK293 under a comparable treatment regiment. Changes in intracellular calcium affecting NP22 biology can be useful in the ongoing characterization of this novel protein.MAS

Cervical cerclage for short cervix at 24-26 weeks of gestation: systematic review and meta-analysis of randomized controlled trials using individual patient-level data.

OBJECTIVE: To determine whether cervical cerclage for a transvaginal ultrasound short cervical length detected after 24 weeks of gestation in singleton pregnancies reduces the risk of preterm birth. DATA SOURCES: Ovid MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials were searched for the following terms: cerclage, cervical , uterine cervical incompetence , obstetrical surgical procedures , cervix uteri , randomized controlled trial , and controlled clinical trial . STUDY ELIGIBILITY CRITERIA: All randomized controlled trials comparing cerclage placement with no cerclage in singleton gestations with a transvaginal ultrasound short cervical length ≤ 25mm between 24 0/7 and 29 6/7 weeks of gestation were eligible for inclusion. STUDY APPRAISAL AND SYNTHESIS METHODS: Individual patient-level data from each trial were collected. If an eligible trial included patients with both multiple and singleton gestations with a short cervical length detected either before or after 24 0/7 weeks of gestation, only singletons who presented at or after 24 0/7 weeks were included. The primary outcome was preterm birth \u3c 37 weeks. Secondary outcomes included preterm birth \u3c 34, \u3c 32, and \u3c 28 weeks, gestational age at delivery, latency, preterm prelabor rupture of membranes, chorioamnionitis, and adverse neonatal outcomes. Individual patient-level data from each trial were analyzed using a two-stage approach. Pooled relative risks (RR) or mean differences with 95% confidence intervals were calculated where appropriate. RESULTS: Data from the four eligible randomized controlled trials were included. One hundred and thirty one singletons presented at 24 0/7 - 26 6/7 weeks of gestation and were further analyzed; there were no data on patients with cerclage at 27 0/7 weeks or later. Of those included, 66 (50.4%) were in the cerclage group, and 65 (49.6%) in the no cerclage group. The rate of preterm birth \u3c 37 weeks was similar between patients who were randomized to cerclage compared with those who were randomized to no cerclage (27.3% vs. 38.5%; RR 0.78, 95% CI 0.37-1.28). Secondary outcomes including preterm birth \u3c 34, \u3c 32, and \u3c 28 weeks, gestational age at delivery, time interval from randomization to delivery, preterm prelabor rupture of membranes, and adverse neonatal outcomes such as low birthweight, very low birthweight, and perinatal death were similar between the two groups. Planned subgroup analyses revealed no statistically significant differences in rate of preterm birth \u3c 37 weeks compared between the two groups based on cervical length measurement (≤ 15mm or ≤ 10mm), gestational age at randomization (24 0/7 - 24 6/7 weeks or 25 0/7 - 26 6/7 weeks), or history of preterm birth. CONCLUSIONS: Cervical cerclage did not reduce or increase the rate of preterm birth in singletons with a short cervical length detected after 24 weeks of gestation. As there was a 22% non-significant decrease in preterm birth associated with cerclage, which is a similar amount of risk reduction often associated with ultrasound-indicated cerclage before 24 weeks, further randomized controlled trials in this patient population are warranted