The mitochondrion of Trypanosoma brucei bloodstream form maintains a membrane potential, although it lacks cytochromes and several Krebs cycle enzymes. At this stage, the ATP synthase is present at reduced, although significant, levels. To test whether the ATP synthase at this stage is important for maintaining the mitochondrial membrane potential, we used RNA interference (RNAi) to knock down the levels of the ATP synthase by targeting the F ₁ -ATPase α and β subunits. RNAi-induced cells grew significantly slower than uninduced cells but were not morphologically altered. RNAi of the β subunit decreased the mRNA and protein levels for the β subunit, as well as the mRNA and protein levels of the α subunit. Similarly, RNAi of α subunit decreased the α subunit transcript and protein levels, as well as the β-subunit transcript and protein levels. In contrast, α and β RNAi knockdown resulted in a 60% increase in the F ₀ complex subunit 9 protein levels without a significant change in the steady-state transcript levels of this subunit. The F ₀ -32-kDa subunit protein expression, however, remained stable throughout induction of RNAi for α or β subunits. Oligomycin-sensitive ATP hydrolytic and synthetic activities were decreased by 43 and 44%, respectively. Significantly, the mitochondrial membrane potential of α and β RNAi cells was decreased compared to wild-type cells, as detected by MitoTracker Red CMXRos fluorescence microscopy and flow cytometry. These results support the role of the ATP synthase in the maintenance of the mitochondrial membrane potential in bloodstream form T. brucei .

Recent studies have yielded conflicting results on the association between anesthesia technique and incidence of postoperative surgical site infections (SSIs) after knee arthroplasty (KA) and hip arthroplasty (HA). Our group conducted a meta-analysis of all available studies to clarify this potential association. Our group searched MEDLINE, EMBASE, and Google Scholar for all relevant studies (1990-2015) reporting on the association between anesthetic technique and SSI after KA or HA. Meta-analysis was performed to estimate both the pooled unadjusted odds ratio (OR) and adjusted OR (aOR) using a random-effects model. Subgroup analyses and metaregression were conducted to explore potential sources of heterogeneity and bias. Of the initial 435 records, 13 studies (n = 362,029) met the inclusion criteria. The use of neuraxial anesthesia was associated with a significant reduction in incidence of postoperative SSI as compared with general anesthesia for all arthroplasties based on unadjusted (OR, 0.77; 95% confidence interval [CI], 0.70-0.86; P < 0.001) and adjusted (aOR = 0.84; 95% CI, 0.76-0.92; P < 0.001) data. Subgroup analyses showed similar reductions in incidence of postoperative SSI for KA (OR = 0.75; 95% CI, 0.68-0.84; P < 0.001; aOR = 0.85; 95% CI, 0.79-0.92; P < 0.001) and HA (OR = 0.79; 95% CI, 0.65 to 0.95; P = 0.02; aOR = 0.84; 95% CI, 0.71-1.00; P = 0.057). Synthesis of the existing evidence supports the overall beneficial effects of neuraxial anesthesia in decreasing the development of SSI after joint arthroplasty (KA and HA). Given the limitations associated with interpretation of data from large observational trials, further investigation using prospective randomized trial design is warranted in this promising area.

Introduction: Peripheral nerve blocks (PNBs) are widely and increasingly used for better acute perioperative pain control for a variety of procedures. Clinically preservative-free dexamethasone is arguably the most commonly used adjuvant and offers the most optimization effects on PNBs yet with the least side-effects noted. Our aim was to compare the effectiveness of intravenous versus perineural dexamethasone on the effectiveness and safety of PNBs. Methods: Major databases (PubMed, EMBASE, Cochrane library, ISI Web of Science, Google Scholar) were systematically searched for randomized controlled trials comparing the effectiveness of intravenous versus perineural dexamethasone on PNBs. Study characteristics, intraoperative events, and postoperative outcomes including duration of analgesia, duration of sensory block, duration of motor block, pain score at 24 hours, opioid consumption, and postoperative nausea and vomiting, were extracted from the articles. Meta-analysis was performed using random-effect models. Results: Thirteen randomized controlled trials comprising a total of 937 patients (intravenous: 464 patients; perineural: 473 patients) were included in this meta-analysis. Perineural dexamethasone significantly prolonged the duration of analgesia (standardized mean difference [SMD], 0.48 h; 95% confidence interval [CI], 0.18-0.79) and sensory block (SMD, 0.74; 95% CI, 0.53-0.94). In subgroup of studies that used 4 to 5 mg we found that perineural dexamethasone was universally more effective to prolong analgesia as compared with intravenous dexamethasone (SMD, 0.48 h; 95% CI, 0.24-0.72), but there was no significant difference between intravenous versus perineural dexamethasone when using a dose of dexamethasone ≥8 mg (SMD, 0.33 h; 95% CI, −0.11 to 0.77). Perineural dexamethasone had similarly more benefits in terms of prolongation of motor block duration, decreasing pain score, reducing opioid consumption, and less postoperative nausea and vomiting. Conclusions: This investigation not only confirmed the better analgesic effects of perineurally administered dexamethasone as compared with its intravenous injection, but also implicitly supported the hypothesis of local interaction between dexamethasone and the nerve as one of the pain modulation mechanisms of dexamethasone, because systemic absorption alone could not explain the superior quality of PNBs.

Background: Spine surgery causes severe pain and can be associated with significant opioid utilization; however, the evidence for opioid-sparing analgesic techniques such as erector spinae plane (ESP) block from controlled studies is limited. We aimed to investigate the analgesic effects of ESP block in lumbar laminoplasty. Methods: In this prospective, double-blind, controlled single-center trial, 62 consecutive elective lumbar laminoplasty patients were randomized into either a control group (Group G, N=32) or a treatment group (Group E, N=30). Group G received general anesthesia and multimodal analgesia, similar to group E, while Group E received additional bilateral ESP block after induction of general anesthesia. The primary outcome was postoperative pain scores for the first 48 h after surgery, and the secondary outcomes analyzed included intraoperative anesthetic usage, perioperative analgesic consumption, return of bowel function and satisfaction for acute pain management indicated by overall benefit of analgesia score (OBAS). Results: Significant differences in pain scores over time were found between the two groups (P=0.010), with Group E patients having significantly lower pain scores than Group G during the first six hours (P=0.000). The opioid consumption in Group G was significantly higher than in Group E both intraoperatively (P=0.000) and postoperatively (P=0.0005). Group E patients had lower intraoperative sevoflurane requirement, improved satisfaction with pain management, and earlier return of bowel function than Group G patients. Conclusion: ESP block is effective in reducing postoperative pain scores and lowering opioid utilization (both intraoperatively and postoperatively), resulting in improved patient satisfaction for pain management in lumbar laminoplasty.