Regulation of NRI/NR2B NMDA receptor function by Thrombin

Ph.DDOCTOR OF PHILOSOPH

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Number of mRNAs altered by differentiation and Bacopa treatment.

<p>Number of mRNAs altered by differentiation and Bacopa treatment.</p

Ingenuity Pathway Analysis: Over-represented biological functions.

<p>Ingenuity Pathway Analysis: Over-represented biological functions.</p

The effect of <i>Bacopa monnieri</i> on gene expression levels in SH-SY5Y human neuroblastoma cells

<div><p><i>Bacopa monnieri</i> is a plant used as a nootropic in Ayurveda, a 5000-year-old system of traditional Indian medicine. Although both animal and clinical studies supported its role as a memory enhancer, the molecular and cellular mechanism underlying Bacopa’s nootropic action are not understood. In this study, we used deep sequencing (RNA-Seq) to identify the transcriptome changes upon Bacopa treatment on SH-SY5Y human neuroblastoma cells. We identified several genes whose expression levels were regulated by Bacopa. Biostatistical analysis of the RNA-Seq data identified biological pathways and molecular functions that were regulated by Bacopa, including regulation of mRNA translation and transmembrane transport, responses to oxidative stress and protein misfolding. Pathway analysis using the Ingenuity platform suggested that Bacopa may protect against brain damage and improve brain development. These newly identified molecular and cellular determinants may contribute to the nootropic action of Bacopa and open up a new direction of investigation into its mechanism of action.</p></div

Summary of SLC-mediated transport functions up-regulated by Bacopa.

<p>Summary of SLC-mediated transport functions up-regulated by Bacopa.</p

Summary of neuronal genes whose mRNAs were altered by Bacopa treatment of SH-SY5Y cells.

<p>Summary of neuronal genes whose mRNAs were altered by Bacopa treatment of SH-SY5Y cells.</p

Results of the gene ontology analysis by Partek Genomics Suite.

<p>The bar graphs indicate the percentage of transcripts that belong to Biological Processes (blue), Cellular Components (red) and Molecular Functions (green) that were most affected by Bacopa treatment.</p

Absolute values of Fold Change (absFC) caused by Bacopa treatment.

<p>RT-PCR was performed on undifferentiated cells and differentiated cells which were treated with vehicle (DMSO) or with Bacopa for either 4 h (blue) or 24 h (orange). The gray area indicated an absFC value smaller than 1. Genes marked with * were results from the treatment on undifferentiated cells. (1) NPTN_A and (2) NPTN_A were results generated from 2 sets of primers priming for NPTN transcript A.</p