Quantitative expression and localization of GABAB receptor protein subunits in hippocampi from patients with refractory temporal lobe epilepsy

This study investigates GABAB protein expression and mRNA levels in three types of specimens. Two types of specimens from patients with temporal lobe epilepsy (TLE), secondary to hippocampal sclerosis, sclerotic hippocampal samples (TLE-HS), and tissue from the structurally preserved non-spiking ipsilateral superior temporal gyrus (TLE-STG) removed from the same patient during epilepsy surgery; and third specimen is hippocampal tissue from individuals with no history of epilepsy (post-mortem controls, PMC). mRNA expression of GABAB subunits was quantified in TLE-HS, TLE-STG and PMC specimens by qRT-PCR. Qualitative and quantitative Western blot (WB) and immunohistochemistry techniques were employed to quantify and localize GABAB proteins subunits. qRT-PCR data demonstrated an overall decrease of both GABAB1 isoforms in TLE-HS compared to TLE-STG. These results were mirrored by the WB findings. GABAB2 mRNA and protein were significantly reduced in TLE-HS samples compared to TLE-STG; however they appeared to be upregulated in TLE-HS compared to the PMC samples. Immunohistochemistry (IHC) showed that GABAB proteins were widely distributed in PMC and TLE-HS hippocampal sections with regional differences in the intensity of the signal. The higher expression of mature GABAB protein in TLE-HS than PMC is in agreement with previous studies. However, these findings could be due to post-mortem changes in PMC specimens. The TLE-STG samples examined here represent a better 'control' tissue compared to TLE-HS samples characterized by lower than expected GABAB expression. This interpretation provides a better explanation for previous functional studies suggesting reduced inhibition in TLE-HS tissue due to attenuated GABAB currents. [Abstract copyright: Copyright © 2017. Published by Elsevier Ltd.

The Effect of Direct Reading Instruction on Students’ Reading Growth

The purpose of this study was to determine if the Read 180/System 44 programs accelerated the reading progress of below grade level struggling readers through additional direct reading instruction and moved the student closer to grade level expectations. This research examined the reading growth demonstrated by students through district and state assessment scores and the impact it had on closing the achievement gap. Participants in the intervention group were fifth and sixth grade students in the researcher’s reading class. Participants in the control group were fifth and sixth grade students not in the researcher’s reading class that demonstrated below grade level reading skills. After gathering baseline reading data to determine the students’ areas of need, instruction focused on meeting the individual needs of each student by focusing on the five essential reading components (phonemic awareness, phonics, fluency, vocabulary, and comprehension). My findings showed that given additional one-on-one direct reading instruction, students’ learning was accelerated closer to their grade level peers

Distinct muscarinic acetylcholine receptor subtypes mediate pre- and postsynaptic effects in rat neocortex

<p>Abstract</p> <p>Background</p> <p>Cholinergic transmission has been implicated in learning, memory and cognition. However, the cellular effects induced by muscarinic acetylcholine receptors (mAChRs) activation are poorly understood in the neocortex. We investigated the effects of the cholinergic agonist carbachol (CCh) and various agonists and antagonists on neuronal activity in rat neocortical slices using intracellular (sharp microelectrode) and field potential recordings.</p> <p>Results</p> <p>CCh increased neuronal firing but reduced synaptic transmission. The increase of neuronal firing was antagonized by pirenzepine (M₁/M₄ mAChRs antagonist) but not by AF-DX 116 (M₂/M₄ mAChRs antagonist). Pirenzepine reversed the depressant effect of CCh on excitatory postsynaptic potential (EPSP) but had marginal effects when applied before CCh. AF-DX 116 antagonized the depression of EPSP when applied before or during CCh. CCh also decreased the paired-pulse inhibition of field potentials and the inhibitory conductances mediated by GABA_A and GABA_B receptors. The depression of paired-pulse inhibition was antagonized or prevented by AF-DX 116 or atropine but only marginally by pirenzepine. The inhibitory conductances were unaltered by xanomeline (M₁/M₄ mAChRs agonist), yet the CCh-induced depression was antagonized by AF-DX 116. Linopirdine, a selective M-current blocker, mimicked the effect of CCh on neuronal firing. However, linopirdine had no effect on the amplitude of EPSP or on the paired-pulse inhibition, indicating that M-current is involved in the increase of neuronal excitability but neither in the depression of EPSP nor paired-pulse inhibition.</p> <p>Conclusions</p> <p>These data indicate that the three effects are mediated by different mAChRs, the increase in firing being mediated by M₁ mAChR, decrease of inhibition by M₂ mAChR and depression of excitatory transmission by M₄ mAChR. The depression of EPSP and increase of neuronal firing might enhance the signal-to-noise ratio, whereas the concomitant depression of inhibition would facilitate long-term potentiation. Thus, this triade of effects may represent a “neuronal correlate” of attention and learning.</p

Ultrafiltration in cardiac surgery: Results of a systematic review and meta-analysis

: Ultrafiltration is used with cardiopulmonary bypass to reduce the effects of hemodilution and restore electrolyte balance. We performed a systematic review and meta-analysis to analyze the effect of conventional and modified ultrafiltration on intraoperative blood transfusion.: Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement, we systematically searched MEDLINE, EMBASE, Web of Science, and Cochrane Library to perform a meta-analysis of studies of randomized controlled trials (RCTs) and observational studies evaluating conventional ultrafiltration (CUF) and modified ultrafiltration (MUF) on the primary outcome of intraoperative red cell transfusions.: A total of 7 RCTs ( = 928) were included, comparing modified ultrafiltration ( = 473 patients) to controls ( = 455 patients) and 2 observational studies ( = 47,007), comparing conventional ultrafiltration ( = 21,748) to controls ( = 25,427). Overall, MUF was associated with transfusion of fewer intraoperative red cell units per patient ( = 7); MD -0.73 units; 95% CI -1.12 to -0.35 = 0.04; for heterogeneity = 0.0001, = 55%) compared to controls. CUF was no difference in intraoperative red cell transfusions compared to controls ( = 2); OR 3.09; 95% CI 0.26-36.59; = 0.37; for heterogeneity = 0.94, = 0%. Review of the included observational studies revealed an association between larger volumes (\u3e2.2 L in a 70 kg patient) of CUF and risk of acute kidney injury (AKI).: The results of this systematic review and meta-analysis suggest that MUF is associated with fewer intraoperative red cell transfusions. Based on limited studies, CUF does not appear to be associated with a difference in intraoperative red cell transfusion