Mary E.

Background: Effectively managing acute postoperative pain after laparoscopic surgery (M-PALS) is essential to optimize outcomes, enhance recovery, and mitigate opioid-related risks. We aimed to systematically map evidence on effectiveness and harms of pharmacologic and non-pharmacologic interventions for M-PALS. Methods: We searched three databases (2012–2025) for randomized clinical trials (RCTs) that reported postoperative opioid use and pain-related outcomes. We assessed study quality using the Cochrane Risk of Bias (ROB)-2 tool. Results: From 7638 citations, we included 101 RCTs. Postoperative opioid use was reported variably (e.g., total use over 24 or 48 h postoperatively, frequency of rescue-opioid use, and time to first rescue-opioid use). One out of 101 RCTs evaluated opioid prescription at discharge. No RCT reported opioid use at ≥3 months postoperatively. Eleven strategies were evaluated in ≥2 RCTs, with usual care/ sham as comparators. None of the 101 RCTs favored usual care over any intervention for pain or opioid use outcomes. For regional anesthesia (21 RCTs total; 12 with low ROB), intraperitoneal/preperitoneal local anesthetic instillation (10 RCTs; 4 with low ROB), intravenous dexamethasone (3 RCTs; 1 with low ROB), and the Enhanced Recovery After Surgery (ERAS) protocol (3 RCTs; 0 with low ROB), compared to usual care, >50% of RCTs favored the intervention for reducing pain and opioid use. For adverse events, only 3 out of 101 RCTs favored comparators. Inconsistent outcome reporting across all RCTs and, for multimodal strategies, the uniqueness of intervention–comparator combinations hindered comparisons. Conclusions: Interventions for M-PALS appear safe, with no RCT indicating worse efficacy of intervention than usual care; but evidence regarding superiority is conflicting. Future research should establish standardized and longer-term core outcome sets and make head-to-head comparisons between optimal strategies.

Bronchopulmonary dysplasia (BPD) is the most common respiratory disease in preterm infants born at less than 28 weeks gestation. Most existing clinical prediction models for BPD show limited accuracy in predicting BPD development when validated using external data, stressing the need for novel biomarkers to identify at-risk infants for early and effective interventions. We leveraged existing frozen umbilical cord blood samples from the Northwestern University Cord Blood Biobank (NUCord) to perform parallel transcriptional and DNA methylation profiling in a pilot study. Chorioamnionitis-associated differentially expressed genes (DEGs) in our cohort included markers previously established in clinical and animal BPD studies, such as genes related to NF-κB signaling and immune responses. Importantly, these genes were highly associated with chorioamnionitis infection status specifically in preterm infants. We also identified that BPD development is associated with disrupted methylation signatures in microRNA genes and genes associated with glucose metabolism. Taken together, these exploratory findings suggest that BPD development and chorioamnionitis are associated with distinct transcriptomic and epigenetic signatures when compared with healthy term and preterm infants. These signatures may represent biomarkers measurable at birth that predict BPD development during a time window when preventative or therapeutic interventions could be applied.

Several thermogenic pathways have been described in adipose tissue, including calcium-mediated thermogenesis in beige adipocytes. We have previously shown that adipocyte-specific deletion of the RNA binding protein human antigen R (HuR; Elavl1) results in thermogenic dysfunction. RNA sequencing revealed the downregulation of several calcium transport genes upon HuR deletion. The goal of this work was to define the HuR-dependent mechanisms of calcium driven thermogenesis in brown adipocytes. Brown adipose tissue (BAT)-specific HuR-deletion (BAT-HuR−/−) mice have no changes in their body weight, glucose tolerance, adipose tissue weights, or lipid droplet size compared to control, but are cold intolerant following acute thermal challenge at 4 °C. We also found decreased expression of ryanodine receptor 2 (Ryr2) in BAT from BAT-HuR−/− mice. We show that genetic deletion or pharmacological inhibition of HuR blunts both the increase in cytosolic calcium and the β-adrenergic-mediated heat generation in stromal vascular fraction (SVF)-derived primary brown adipocytes. Mechanistically, we show that HuR directly binds and reduces the decay rate of Ryr2 mRNA in brown adipocytes, and stabilization of Ryr2 via S107 rescues the observed changes. In conclusion, our results suggest that HuR-dependent control of Ryr2 expression plays a significant role in the thermogenic function of brown adipose tissue through modulation of sarcoendoplasmic-reticulum calcium cycling.

Biodiversity indicators are essential for tracking progress towards international biodiversity goals, but existing indicators have important shortcomings and are not based on animal movement data. This Perspective outlines why incorporating movement data into biodiversity indicators can help to address these shortcomings, improve monitoring and inform effective conservation actions.

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