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Circadian clocks coordinate behavioral and physiological processes with daily light-dark cycles by driving rhythmic transcription of thousands of genes. Whereas the master clock in the brain is set by light, pacemakers in peripheral organs, such as the liver, are reset by food availability, although the setting, or \"entrainment,\" mechanisms remain mysterious. Studying mouse fibroblasts, we demonstrated that the nutrient-responsive adenosine monophosphate-activated protein kinase (AMPK) phosphorylates and destabilizes the clock component cryptochrome 1 (CRY1). In mouse livers, AMPK activity and nuclear localization were rhythmic and inversely correlated with CRY1 nuclear protein abundance. Stimulation of AMPK destabilized cryptochromes and altered circadian rhythms, and mice in which the AMPK pathway was genetically disrupted showed alterations in peripheral clocks. Thus, phosphorylation by AMPK enables cryptochrome to transduce nutrient signals to circadian clocks in mammalian peripheral organs.

Preperitoneal pelvic packing (PPP) has been advocated as a damage control procedure for pelvic fracture bleeding, despite of weak evidence. Matched cohort study, TQIP database. Patients with isolated severe blunt pelvic fractures (pelvis abbreviated injury score [AIS] ​≥ ​3, AIS ≤2 in all other body regions) were included. Patients who underwent PPP were matched to patients with no PPP, 1:3 nearest propensity score. Matching was performed based on demographics, vital signs on admission, comorbidities, injury characteristics, type and timing of initiation of VTE prophylaxis, and additional procedures including laparotomy, REBOA, and angioembolization. 64 patients with PPP were matched with 182 patients with No-PPP. PPP patients had higher in-hospital mortality (14.1 ​% vs 2.2 ​% p ​< ​0.001) and higher rates of VTE and DVT (VTE: 14.1 ​% vs 4.4 ​% p ​= ​0.018, DVT: 10.9 ​% vs 2.2 ​% p ​= ​0.008). PPP is associated with worse survival outcomes and increased rate of VTE and DVT complications. Preperitoneal Packing in Pelvic Fractures.•Higher Mortality•Higher incidence of venous thromboembolic complications.

IntroductionSince their release in 2017, standing electric motorized scooters (eScooters) have risen in popularity as an alternative mode of transportation. We sought to examine the incidence of injury, injury patterns, prevalence of helmet and drug and alcohol use in eScooter trauma.MethodsThis was a multi-institutional retrospective case series of patients admitted for injuries related to operation of an eScooter following the widespread release of these devices in September 2017 (September 1, 2017 to October 31, 2018). Demographics, drug and alcohol use, helmet use, admission vitals, injuries, procedures, hospital and intensive care unit length of stay (LOS), death, and disposition were analyzed.Results103 patients were admitted during the study period, and monthly admissions increased significantly over time. Patients were young men (mean age 37.1 years; 65% male), 98% were not wearing a helmet. Median LOS was 1 day (IQR 1–3). 79% of patients were tested for alcohol and 48% had a blood alcohol level >80 mg/dL. 60% of patients had a urine toxicology screen, of which 52% were positive. Extremity fractures were the most frequent injury (42%), followed by facial fractures (26%) and intracranial hemorrhage (18%). Median Injury Severity Score was 5.5 (IQR 5–9). One-third of patients (n=34) required an operative intervention, the majority of which were open fixations of extremity and facial fractures. No patients died during the study. The majority of patients were discharged home (86%).ConclusioneScooter-related trauma has significantly increased over time. Alcohol and illicit substance use among these patients was common, and helmet use was extremely rare. Significant injuries including intracranial hemorrhage and fractures requiring operative intervention were present in over half (51%) of patients. Interventions aimed at increasing helmet use and discouraging eScooter operation while intoxicated are necessary to reduce the burden of eScooter-related trauma.Level of evidenceLevel IV.

ObjectiveHydroxychloroquine (HCQ) is a mainstay of therapy in the treatment of SLE. The effect of HCQ on platelets and vascular health is uncertain. We investigated the relationship between HCQ use and dose with platelet activity, platelet transcriptomics and vascular health in patients with SLE.MethodsPlatelet aggregation, platelet mRNA expression and vascular health (sublingual capillary perfused boundary region (PBR), red blood cell filling (RBCF) and brachial artery reactivity testing) were analysed by HCQ use and dose.ResultsAmong 132 subjects with SLE (age: 39.7±12.9 years, 97% female), 108 were on HCQ. SLE disease activity was similar between subjects on and off HCQ. Platelet aggregation in response to multiple agonists was significantly lower in patients on HCQ. There were inverse relationships between HCQ dose and gene expression pathways of platelet activity. Gene expression of P-selectin (SELP) was inversely correlated with HCQ dose (r=−0.41, p=0.003), which was validated at the protein level. Subjects on HCQ had improved vascular function correlating with HCQ dose as measured by lower PBR (r=−0.52, p=0.007), higher RBCF (r=0.55, p=0.004) and greater brachial artery reactivity (r=0.43, p=0.056).ConclusionHCQ use was associated with decreased platelet activation and activation-related transcripts and improved vascular health in SLE.

IntroductionThe analysis of surgical research using bibliometric measures has become increasingly prevalent. Absolute citation counts (CC) or indices are commonly used markers of research quality but may not adequately capture the most impactful research. A novel scoring system, the disruptive score (DS) has been found to identity academic work that either changes paradigms (disruptive (DIS) work) or entrenches ideas (developmental (DEV) work). We sought to analyze the most DIS and DEV versus most cited research in civilian trauma.MethodsThe top papers by DS and by CC from trauma and surgery journals were identified via a professional literature search. The identified publications were then linked to the National Institutes of Health iCite tool to quantify total CC and related metrics. The top 100 DIS and DEV publications by DS were analyzed based on the area of focus, citation, and perceived clinical impact, and compared with the top 100 papers by CC.Results32 293 articles published between 1954 and 2014 were identified. The most common publication location of selected articles was published in Journal of Trauma (31%). Retrospective reviews (73%) were common in DIS (73%) and top CC (67%) papers, while DEV papers were frequently case reports (49%). Only 1 publication was identified in the top 100 DIS and top 100 CC lists. There was no significant correlation between CC and DS among the top 100 DIS papers (r=0.02; p=0.85), and only a weak correlation between CC and DS score (r=0.21; p<0.05) among the top 100 DEV papers.ConclusionThe disruption score identifies a unique subset of trauma academia. The most DIS trauma literature is highly distinct and has little overlap with top trauma publications identified by standard CC metrics, with no significant correlation between the CC and DS.Level of evidenceLevel IV.

Background The clinical heterogeneity of SLE with its complex pathogenesis remains challenging as we strive to provide optimal management. The contribution of platelets to endovascular homeostasis, inflammation and immune regulation highlights their potential importance in SLE. Prior work from our group showed that the Fcγ receptor type IIa (FcγRIIa)–R/H131 biallelic polymorphism is associated with increased platelet activity and cardiovascular risk in SLE. The study was initiated to investigate the platelet transcriptome in patients with SLE and evaluate its association across FcγRIIa genotypes and distinct clinical features. Methods Fifty-one patients fulfilling established criteria for SLE (mean age = 41.1 ± 12.3, 100% female, 45% Hispanic, 24% black, 22% Asian, 51% white, mean SLEDAI = 4.4 ± 4.2 at baseline) were enrolled and compared with 18 demographically matched control samples. The FCGR2a receptor was genotyped for each sample, and RNA-seq was performed on isolated, leukocyte-depleted platelets. Transcriptomic data were used to create a modular landscape to explore the differences between SLE patients and controls and various clinical parameters in the context of FCGR2a genotypes. Results There were 2290 differentially expressed genes enriched for pathways involved in interferon signaling, immune activation, and coagulation when comparing SLE samples vs controls. When analyzing patients with proteinuria, modules associated with oxidative phosphorylation and platelet activity were unexpectedly decreased. Furthermore, genes that were increased in SLE and in patients with proteinuria were enriched for immune effector processes, while genes increased in SLE but decreased in proteinuria were enriched for coagulation and cell adhesion. A low-binding FCG2Ra allele (R131) was associated with decreases in FCR activation, which further correlated with increases in platelet and immune activation pathways. Finally, we were able to create a transcriptomic signature of clinically active disease that performed significantly well in discerning SLE patients with active clinical disease form those with inactive clinical disease. Conclusions In aggregate, these data demonstrate the platelet transcriptome provides insight into lupus pathogenesis and disease activity, and shows potential use as means of assessing this complex disease using a liquid biopsy.

INTRODUCTION Library digital collections have historically contained unstandardized and often inadequate information regarding copyright status in the item-level metadata. The development of RightsStatements.org, international recommendations for describing rights status, provides an opportunity for libraries to improve their rights metadata and educate users about copyright for digital objects. DESCRIPTION OF PROGRAM This paper reports on a two-year project at the University of Miami Libraries to implement RightsStatements.org. Two librarians, who did not previously have a background in copyright issues, performed a copyright analysis of all 58,000 objects in the libraries' digital collections and developed workflows for updating rights metadata. Workflows for developing new digital projects were also updated to incorporate rights considerations more comprehensively throughout the process. CONCLUSIONS AND NEXT STEPS The copyright assessment project uncovered several challenges for analyzing the copyright status of digitized archival and special collections materials, including the need to periodically reevaluate materials as more content moves into the public domain in the United States. The project also reinforced the importance of risk management when planning digitization projects for online access. Project outcomes are discussed, as well as implications for other libraries considering implementing RightsStatements.org.

A longstanding challenge is to understand how ribosomes parse mRNA open reading frames (ORFs). Significantly, GCN codons are over-represented in the initial codons of ORFs of prokaryote and eukaryote mRNAs. We describe a ribosome rRNA-protein surface that interacts with an mRNA GCN codon when next in line for the ribosome A-site. The interaction surface is comprised of the edges of two stacked rRNA bases: the Watson–Crick edge of 16S/18S rRNA C1054 and the adjacent Hoogsteen edge of A1196 (Escherichia coli 16S rRNA numbering). Also part of the interaction surface, the planar guanidinium group of a conserved Arginine (R146 of yeast ribosomal protein Rps3) is stacked adjacent to A1196. On its other side, the interaction surface is anchored to the ribosome A-site through base stacking of C1054 with the wobble anticodon base of the A-site tRNA. Using molecular dynamics simulations of a 495-residue subsystem of translocating ribosomes, we observed base pairing of C1054 to nucleotide G at position 1 of the next-in-line codon, consistent with previous cryo-EM observations, and hydrogen bonding of A1196 and R146 to C at position 2. Hydrogen bonding to both of these codon positions is significantly weakened when C at position 2 is changed to G, A or U. These sequence-sensitive mRNA-ribosome interactions at the C1054-A1196-R146 (CAR) surface potentially contribute to the GCN-mediated regulation of protein translation.

Purpose The purpose of this paper is to investigate perceptions towards a career in psychiatry among medical students and psychiatrists and identify how recruitment into the specialty may be improved. Design/methodology/approach This study locally compares medical student and psychiatric doctor responses to a structured online survey and structured interviews with key managerial figures in the Humber NHS Foundation Trust. Findings Comparison across two main areas (pre-decision exposure to psychiatry and reasons for considering a psychiatric career) found that both students and doctors were influenced to make a choice about a career in psychiatry during medical school. Medical students found compatibility with family life to be more important when considering psychiatry, whereas doctors cited content-based reasons as significant pull factors. Stigma and fear of being harmed deterred some students from choosing a career in psychiatry. Structured interview responses reiterated the importance of pre-medical school and undergraduate mentorship in bolstering future recruitment to psychiatry. Practical implications Medical students perceive certain career issues differently to their postgraduate counterparts. Widening the content-based appeal of psychiatry and optimising the medical school experience of the specialty via varied and high-quality placements may be a key step towards tackling the national shortfall in qualified psychiatrists. Originality/value This is the first published study comparing medical student and psychiatric doctor perceptions of a career in psychiatry.