Summary To metastasize, a tumor cell must acquire abilities such as the capacity to colonize new tissue and evade immune surveillance. Recent evidence suggests that microRNAs can promote the evolution of malignant behaviors by regulating multiple targets. We performed a microRNA analysis of human melanoma, a highly invasive cancer, and found that miR-30b/30d upregulation correlates with stage, metastatic potential, shorter time to recurrence and reduced overall survival. Ectopic expression of miR-30b/30d promoted the metastatic behavior of melanoma cells by directly targeting the GalNAc transferase GALNT7, resulted in increased synthesis of the immunosuppressive cytokine IL-10, and reduced immune cell activation and recruitment. These data support a key role of miR-30b/30d and GalNAc transferases in metastasis, by simultaneously promoting cellular invasion and immunosuppression.

Summary SLBP (stem-loop binding protein) is a highly conserved factor necessary for the processing, translation, and degradation of H2AFX and canonical histone mRNAs. We identified the F-box protein cyclin F, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the G2 ubiquitin ligase for SLBP. SLBP interacts with cyclin F via an atypical CY motif, and mutation of this motif prevents SLBP degradation in G2. Expression of an SLBP stable mutant results in increased loading of H2AFX mRNA onto polyribosomes, resulting in increased expression of H2A.X (encoded by H2AFX). Upon genotoxic stress in G2, high levels of H2A.X lead to persistent γH2A.X signaling, high levels of H2A.X phosphorylated on Tyr142, high levels of p53, and induction of apoptosis. We propose that cyclin F co-evolved with the appearance of stem-loops in vertebrate H2AFX mRNA to mediate SLBP degradation, thereby limiting H2A.X synthesis and cell death upon genotoxic stress.

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Purpose: To characterize the volume and variation in orthopedic consults and surgeries that took place during a period of social distancing and pandemic. Methods: All orthopedic consults and surgeries at an urban level 1 trauma center from 3/22/20-4/30/2020 were retrospectively reviewed (the social distancing period). Data from the same dates in 2019 were reviewed for comparison. Age, gender, Score for Trauma Triage in the Geriatric and Middle Aged (STTGMA) score and injury type were queried. Operating room data collected included: type of surgery performed, inpatient or outpatient status, and if the cases were categorized as elective, trauma or infectious cases. Results: Compared to 2019, there was a 48.3% decrease in consult volume in 2020. The 2020 population was significantly older (44.0 vs 52.6 years-old, p = 0.001) and more male (65% vs 35%, p = 0.021). There were 23 COVID positive patients, 10 of which died within the collection period. Consult distribution dramatically changed, with decreases in ankle fractures, distal radius fractures and proximal humerus fractures of 76.5%, 77.4% and 55.0%, respectively. However, there was no significant difference in volume of hip, tibial shaft and femoral shaft fractures (p > 0.05). In 2020, there was a 41.4% decrease in operating room volume, no elective cases were performed, and cases were primarily trauma related. Conclusions: During a period of pandemic and social distancing, the overall volume of orthopedic consults and surgeries significantly declined. However, hip fracture volume remained unchanged. Patients presenting with orthopedic injuries were older, and at higher risk for inpatient mortality.

ObjectiveTo determine whether translocation of bacteria or endotoxin occurred into the thoracic duct in patients with multiple organ failure (MOF). Summary Background DataTranslocation of bacteria or endotoxin has been proposed as a causative factor for MOF in patients without an infectious focus, although it has rarely been demonstrated in patients at risk for MOF. Most studies have investigated the hematogenic route of translocation, but it has been argued that lymphatic translocation of bacteria or endotoxin by the thoracic duct is the major route of translocation. MethodsThe thoracic duct was drained for 5 days in patients with MOF caused either by generalized fecal peritonitis (n = 4) or by an event without clinical and microbiologic evidence of infection (n = 4). Patients without MOF who were undergoing a transthoracic esophageal resection served as controls. In lymph and blood, concentrations of endotoxin, proinflammatory cytokines, and antiinflammatory cytokines were measured. ResultsEndotoxin concentrations in lymph and blood of patients with MOF ranged from 39 to 63 units per liter and were not significantly different from concentrations in patients without MOF. The quantity of endotoxin transported by the thoracic duct in the study group was small. In patients with MOF, low levels of proinflammatory cytokines and high levels of antagonists of these cytokines were found. ConclusionThis study provides evidence that translocation (especially of endotoxin) occurs into the thoracic duct. However, these data do not support the concept that the thoracic duct is a major route of bacterial translocation in patients with MOF.Although important new insights into the pathogenesis of multiple organ failure (MOF) have evolved," 2 the initiating trigger for the development of MOF in patients without an infectious focus remains an unanswered question. We know that the release of inflammatory mediators plays a key role in this process and results in a massive inflammatory reaction, producing multiple organ dysfunction and ultimately MOF. However, the initial event causing cytokine release in Address reprint requests to Lucienne C.J.M. Lemaire,