Comparative evaluation of continuous infusion versus programmed intermittent bolus techniques in erector spinae plane block in modified radical mastectomy - A preliminary randomised controlled trial.

Background and Aims: Single-shot erector spinae plane block (ESPB) provides excellent analgesia in mastectomy in the immediate post-operative period but is not sufficient to maintain for prolonged duration. This study compares the efficacy of programmed intermittent bolus (PIB) versus continuous infusion (CI) techniques after ESPB by placing a catheter for mastectomy. Methods: After ethical approval and patient consent, ESPB was performed at the T4 level in 50 patients with an initial bolus of 20 mL 0.375% ropivacaine and a catheter placed 30 min before surgery. In the postoperative period, they were randomised to Group I - intermittent bolus of 20 mL 0.2% ropivacaine every 4 h for 24 h and Group C - continuous infusion of 0.2% ropivacaine at 5 mL/h for 24 h. The primary outcome was the 24-h fentanyl consumption by patient-controlled analgesia device. Data was analysed using Stata 14.0. Results: Group I patients had reduced post-operative fentanyl consumption {mean [standard deviation (SD)]: 166 (139.17) µg vs 332 (247.96) µg, P = 0.002} and lower median NRS scores (1 h: 3 vs 5), (2 h: 3 vs 5), (4 h: 3 vs 5), (6 h: 4 vs 5) with a higher mean (SD) Quality of Recovery-15 score {134.4 (8.53) vs 127 (12.89), P = 0.020} compared to Group C, respectively. The 24-h dermatomal sensory coverage was more comprehensive in Group I compared to Group C. Conclusion: The PIB technique after ESPB provides decreased postoperative opioid consumption, better post-operative analgesia and quality of recovery compared to the CI technique in patients undergoing mastectomy.

Diacylglycerol kinase alleviates autophagic degradation of the endoplasmic reticulum in SPT10-deficient yeast to enhance triterpene biosynthesis.

A recent study showed that deletion of the gene encoding the transcription regulator SuPpressor of Ty10 (SPT10) increases total phospholipids, and our previous study established a critical link between phospholipids and the mevalonate/ergosterol (MEV/ERG) pathway, which synthesises triterpenes. This study aims to use spt10Δ yeast to improve triterpene production. Though MEV/ERG pathway was highly expressed in spt10Δ yeast, results showed insufficient accumulation of key metabolites and also revealed massive endoplasmic reticulum (ER) degradation. We found a stable, massive ER structure when we overexpressed diacylglycerol kinase1 (DGK1OE ) in spt10Δ yeast. Analyses of ER-stress and autophagy suggest that DGK1OE in the spt10Δ strain decreased autophagy, resulting in increased MEV/ERG pathway activity. Heterologous expression of ß-amyrin synthase showed significant production of the triterpene ß-amyrin in DGK1OE spt10Δ yeast. Overall, our study provides a strategic approach to improve triterpene production by increasing ER biogenesis while limiting ER degradation.

Triglyceride deficiency and diacylglycerol kinase1 activity lead to the upregulation of mevalonate pathway in yeast: A study for the development of potential yeast platform for improved production of triterpenoid.

Besides energy storage and membrane biogenesis, lipids are known for their numerous biological functions. The two essential lipids, diacylglycerol (DG) and phosphatidic acid (PA), are shown to be associated with cell signalling processes. In this study, we examined whether triglyceride-deficient yeast mutants (tgΔ), dga1Δ and dga1Δlro1Δ, may play an important role in mevalonate (MEV) pathway regulation. Our metabolite analyses revealed that tgΔ cells showed high levels of squalene (SQ) and ergosterol (ERG), which are key indicators of MEV pathway activity. In addition, gene expression studies indicated that the MEV pathway genes in tgΔ cells were significantly upregulated. Interestingly, tgΔ cells exhibited high diacylglycerol kinase1 (DGK1) expression. Furthermore, DGK1 overexpression in WT and tgΔ phenotypes causes a substantial elevation in SQ and ERG levels, and we also found a significant increase in transcript levels of MEV pathway genes, confirming the new role of DGK1 in MEV pathway regulation. This suggests that high DG phosphorylation activity increases the PA pool that may induce the upregulation of MEV pathway in tgΔ cells. The induced MEV pathway is one of the key strategies in the field of synthetic biology for improved production of terpenoids in yeast. Thus, to examine whether increased endogenous MEV pathway flux can be redirected to triterpenoid, ß-Amyrin synthase gene was heterologously expressed in DGK1 overexpressing tgΔ cells that led to significant production of ß-Amyrin, a natural triterpenoid. In conclusion, our findings provide a novel strategy to increase MEV pathway precursors by modulating endogenous signal lipids for improved production of terpenoids.