An efficient expression-secretion system for heterologous protein production in food-grade hosts, Lactobacillus plantarum and Bacillus subtilis, is still required to broaden their applications. The optimal signal peptide compatible with both the desired protein and the target host is important for the system. Here, we constructed new expression-secretion vectors to be used in both bacteria. A natural plasmid originating from food-grade L. plantarum BCC9546 was used as a core vector combined with a strong constitutive promoter, L-ldh promoter, and various signal peptides from several types of L. plantarum proteins ABC transporter, cell wall-associated and extracellular proteins. A gene encoding 88-kDa amylase isolated from starch-related L. plantarum TBRC470 was used as a gene model to evaluate the systems. By comparing the amounts of secreted amylase from the recombinant strains to that of wild type, all signal peptides gave higher yields of secreted amylase in recombinant B. subtilis. Interestingly, two ABC transporter signal peptides from glutamine and mannose ABC transporters provided noticeably high levels of secreted amylase in recombinant L. plantarum. Moreover, these signal peptides also gave high yields of secreted amylase in recombinant B. subtilis. From the results, the signal peptide of glutamine ABC transporter, which functions in essential amino acid transportation that is a precursor for synthesis of nitrogen-containing compounds and nitrogen homeostasis, has a potential use in development of an efficient expression-secretion system for heterologous protein production in both food-grade hosts.At July 25, 2020, WHO had recorded more than 16.1 million confirmed COVID-19 cases, 1% of them developed critical illness. These patients can experience rapid progression to profound hypoxemia and severe acute respiratory distress syndrome (ARDS). Some patients, despite receiving lung-protective ventilation and maximal medical therapy, develop refractory hypoxemia, rendering candidates for extracorporeal membrane oxygenation (ECMO) support. Centers with experience in this technique are available only in a few reference hospitals and some patients are too ill to be transferred with conventional mechanical ventilation so they need mobile ECMO (interhospital transport under ECMO). Here we report the first interhospital extracorporeal membrane oxygenation transport of a COVID-19 patient in Chile, showing that it is feasible and safe to transfer a COVID-19 patient under ECMO support if a mobile ECMO program is correctly implemented and the particularities of protective measures are properly taken.

Local infiltration analgesia (LIA) has been proven to be efficient in total knee arthroplasty (TKA). However, the effect of single-shot LIA is temporarily limited. The objective of this prospective trial was to investigate if the potential benefits resulting from LIA can be prolonged by a continuous intra-articular perfusion of LIA. The hypothesis of the present study was that the use of an additional continuous intra-articular perfusion delivering LIA would result in less pain and better function compared to single-shot LIA in the immediate post-operative period.

50 consecutively selected patients undergoing TKA received either a single-shot LIA (S-LIA group, 25 knees) or single-shot LIA combined with a continuous post-operative intra-articular perfusion for three post-operative days (CP-LIA group, 25 knees). VAS (visual analogue scale) for pain, pain medication consumption and flexion ability were recorded postoperatively for 6days. All patients had the same implant, surgeon and intra- as well as post-operative setting.

The VAS score was significantly better for CP-LIA 6h after surgery and on post-operative day 1, 2 and 6. There was no significant difference with regard to additional opioid consumption or flexion ability of the knee. However, there was a trend of the CP-LIA group requiring less additional opioids over the complete post-operative period compared to the S-LIA group. There were no complications or revisions.

LIA combined with an additional intra-articular catheter provides better short-term pain control compared to single-shot LIA. However, no significant differences in terms of knee flexion were observed. This limited benefit should be balanced against the additional costs and the possible higher risk of infection.

Level II.

Level II.

To compare pharmacokinetics, safety, tolerability, and immunogenicity between SB8, a bevacizumab biosimilar, and the European Union (EU) and United States (US) reference products (bevacizumab-EU, bevacizumab-US).

In this randomized, double-blind, parallel-group, and single-dose study, healthy volunteers were randomized to receive a 3mg/kg dose of SB8, bevacizumab-EU, or bevacizumab-US via intravenous infusion. Primary endpoints were area under the concentration-time curve from time zero to infinity (AUC

) and to the last quantifiable concentration (AUC

), and maximum observed serum concentration (C

). Bioequivalence was achieved if 90% confidence intervals (CIs) for the ratios of the geometric least squares means (LSMeans) of primary endpoints were within the predefined bioequivalence margins of 80.00-125.00%. Safety and immunogenicity were also investigated.

The 90% CIs for the geometric LSMean ratios of AUC

, AUC

and C

were all within the prespecified bioequivalence margins. Geometric LSMean ratios for SB8/bevacizumab-EU, SB8/bevacizumab-US and bevacizumab-EU/bevacizumab-US were 88.01%, 88.48% and 100.54% for AUC

, 88.65%, 89.08% and 100.49% for AUC

and 99.59%, 101.15% and 101.56% for C

, respectively. selleckchem Incidence of treatment-emergent adverse events (TEAEs) across treatment groups was comparable (SB8 50.0%, bevacizumab-EU 37.5%, bevacizumab-US 53.8%). Most TEAEs were mild and considered as not related to the study drug. No deaths or treatment discontinuations due to adverse events occurred. Incidence of anti-drug antibodies was also comparable between all groups and no neutralizing antibodies were detected.

This study demonstrated pharmacokinetic bioequivalence and similar safety and immunogenicity profiles of SB8 to both reference products, bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US. CLINICALTRIALS.

NCT02453672 (submitted date); EudraCT number 2015-001,026-41.

NCT02453672 (submitted date); EudraCT number 2015-001,026-41.