“Bull's-eye” sign on gadolinium-enhanced magnetic resonance venography determines thrombus presence and age: A preliminary study

AbstractPurpose: Venous thrombosis is associated with a significant inflammatory response, which can be visualized by gadolinium magnetic resonance venography (MRV). Gadolinium extravasates into tissue during inflammation, producing perithrombus enhancement on magnetic resonance scanning. This study determines (1) whether gadolinium enhancement occurs during deep venous thrombosis (DVT); and (2) whether this enhancement changes with time and can therefore establish the age of thrombus.Methods: Patients with a diagnosis of iliofemoral DVT by duplex ultrasound who were referred for MRV to document central thrombus extent were studied. T1 weighted images were obtained before and after gadolinium injection (0.1 mmol/kg); repeat scans were obtained up to 3 months thereafter. At the level of maximum thrombus, measurements of signal intensity were made at the periphery (rim), and the center of the thrombosed vein, as well as the contralateral normal vein, on images after gadolinium enhancement. Rim-center vein signal intensity ratios were then calculated and followed.Results: A total of 39 scans were obtained in 14 patients (eight men, six women). The thrombosed veins were enlarged, with a peripheral rim of enhancement (“bull's-eye” sign). The rim-center ratio for thrombosed veins (2.16 ± 0.18) was different from that of normal veins (0.66 ± 0.10; n = 39; p < 0.001). For all acute studies (≤14 days) the rim-center ratio was 2.38 ± 0.17 (n = 31), whereas for all chronic studies (>14 days) the rim-center ratio was 1.29 ± 0.44 (n = 8; p = 0.001). Among patients who underwent both early and late studies, the rim-center ratio dropped significantly, from 2.33 ± 0.20 acutely to 1.29 ± 0.44 in chronic studies (n = 8; p = 0.03). One patient with active malignancy had a paradoxic increase in rim-center ratio over time and a clinical recurrence of symptoms, suggesting active thrombosis.Conclusions: We conclude that (1) a pattern of peripheral gadolinium enhancement (bull's-eye sign) is seen around acutely thrombosed veins on gadolinium-enhanced MRV, facilitating DVT diagnosis; and (2) the ratio of signal intensity at the rim versus the center of the thrombosed vein may be a good discriminator of acute compared with chronic DVT, which may help direct therapy. (J Vasc Surg 1997;26:809-16.

Bacterial quorum-sensing signal arrests phytoplankton cell division and impacts virus-induced mortality

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Pollara, S. B., Becker, J. W., Nunn, B. L., Boiteau, R., Repeta, D., Mudge, M. C., Downing, G., Chase, D., Harvey, E. L., & Whalen, K. E. Bacterial quorum-sensing signal arrests phytoplankton cell division and impacts virus-induced mortality. Msphere, 6(3), (2021): e00009-21, https://doi.org/10.1128/mSphere.00009-21.Interactions between phytoplankton and heterotrophic bacteria fundamentally shape marine ecosystems by controlling primary production, structuring marine food webs, mediating carbon export, and influencing global climate. Phytoplankton-bacterium interactions are facilitated by secreted compounds; however, linking these chemical signals, their mechanisms of action, and their resultant ecological consequences remains a fundamental challenge. The bacterial quorum-sensing signal 2-heptyl-4-quinolone (HHQ) induces immediate, yet reversible, cellular stasis (no cell division or mortality) in the coccolithophore Emiliania huxleyi; however, the mechanism responsible remains unknown. Using transcriptomic and proteomic approaches in combination with diagnostic biochemical and fluorescent cell-based assays, we show that HHQ exposure leads to prolonged S-phase arrest in phytoplankton coincident with the accumulation of DNA damage and a lack of repair despite the induction of the DNA damage response (DDR). While this effect is reversible, HHQ-exposed phytoplankton were also protected from viral mortality, ascribing a new role of quorum-sensing signals in regulating multitrophic interactions. Furthermore, our data demonstrate that in situ measurements of HHQ coincide with areas of enhanced micro- and nanoplankton biomass. Our results suggest bacterial communication signals as emerging players that may be one of the contributing factors that help structure complex microbial communities throughout the ocean.Funding for this work was supported by an NSF grant (OCE-1657808) awarded to K.E.W. and E.L.H. K.E.W. was also supported by a faculty research grant from Haverford College as well as funding from the Koshland Integrated Natural Science Center and Green Fund at Haverford College. E.L.H. was also supported by a Sloan Foundation research fellowship. B.L.N. was supported by an NSF grant (OCE-1633939). M.C.M. was supported by an NIH training grant (T32 HG000035). Mass spectrometry was partially supported by the University of Washington Proteomics Resource (UWPR95794). D.R. was supported by funding through the Gordon and Betty Moore Foundation (grant 6000), a Simons Collaboration for Ocean Processes and Ecology grant (329108), and an NSF grant (OCE-1736280). R.B. was supported by an NSF graduate research fellowship and an NSF grant (OCE-1829761)

Extracellular vesicles from human cardiac fibroblasts modulate calcium cycling in human stem cell-derived cardiomyocytes

Cardiac fibroblasts regulate the development of the adult cardiomyocyte phenotype and cardiac remodeling in disease. We investigate the role that cardiac fibroblasts-secreted extracellular vesicles (EVs) have in the modulation of cardiomyocyte Ca2+ cycling–a fundamental mechanism in cardiomyocyte function universally altered during disease. EVs collected from cultured human cardiac ventricular fibroblasts were purified by centrifugation, ultrafiltration and size-exclusion chromatography. The presence of EVs and EV markers were identified by dot blot analysis and electron microscopy. Fibroblast-conditioned media contains liposomal particles with a characteristic EV phenotype. EV markers CD9, CD63 and CD81 were highly expressed in chromatography fractions that elute earlier (Fractions 1–15), with most soluble contaminating proteins in the later fractions collected (Fractions 16–30). Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were treated with fibroblast-secreted EVs and intracellular Ca2+ transients were analyzed. Fibroblast-secreted EVs abbreviate the Ca2+ transient time to peak and time to 50% decay versus serum-free controls. Thus, EVs from human cardiac fibroblasts represent a novel mediator of human fibroblast-cardiomyocyte interaction, increasing the efficiency of hiPSC-CM Ca2+ handling

The psychological impact of being on a monitoring pathway for localised prostate cancer: a UK-wide mixed methods study

Objective: To address concerns over the psychological impact of being on a monitoring pathway following prostate cancer (PCa) diagnosis, this study compared the psychological status of men on active surveillance (AS) or watchful waiting (WW) with men on active treatment (AT), and explored psychological adjustment in men on AS/WW. Methods: Cross-sectional survey of UK men diagnosed with PCa 18-42 months previously (n=16,726, localised disease at diagnosis) and telephone interviews with 24 men on AS/WW. Psychological outcomes were measured using two validated scales (Short Warwick-Edinburgh Mental-Well-being Scale; Kessler Psychological Distress Scale). Univariable and multivariable analyses compared outcomes between men on AS/WW and AT. Thematic analysis of interviews was undertaken, informed by a previously developed theory of adjustment to cancer. Results: 3,986 (23.8%) respondents were on AS/WW. Overall, psychological outcomes were similar or better in men on AS/WW compared to those receiving AT (SWEMWBS: Poor well-being; 12.3% AS/WW vs 13.9% AT, adjusted OR=0.86, 95% CI 0.76-0.97; K6: severe psychological distress; 4.6% vs 5.4%, adjusted OR=0.90, 95% CI 0.74-1.08). Interviews indicated most men on AS/WW had adjusted positively. Men with poorer well-being were less able to accept, reframe positively and normalise the diagnosis, described receiving insufficient information and support, and a lack of confidence in their health-care professionals. Conclusions: Most men on AS/WW cope well psychologically. Men making treatment decisions should be given this information. Psychological health should be assessed to determine suitability for AS/WW, and at monitoring appointments. A clear action plan and support from healthcare professionals is important

Role of the Laboratory in Ensuring Global Access to ARV Treatment for HIV-Infected Children: Consensus Statement on the Performance of Laboratory Assays for Early Infant Diagnosis

A two day meeting hosted by the World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention (CDC) was held in May 2006 in Entebbe, Uganda to review the laboratory performance of virologic molecular methods, particularly the Roche Amplicor DNA PCR version 1.5 assay, in the diagnosis of HIV-1 infection in infants. The meeting was attended by approximately 60 participants from 17 countries. Data on the performance and limitations of the HIV-1 DNA PCR assay from 9 African countries with high-burdens of HIV/AIDS were shared with respect to different settings and HIV- subtypes. A consensus statement on the use of the assay for early infant diagnosis was developed and areas of needed operational research were identified. In addition, consensus was reached on the usefulness of dried blood spot (DBS) specimens in childhood as a means for ensuring greater accessibility to serologic and virologic HIV testing for the paediatric population

Identifying Youth at Clinical High Risk: What’s the Emotional Impact?

Background: Early intervention in major mental illness promises to improve the lives of those identified. • But could identifying youth as at clinical high risk (CHR) for psychosis also do harm given that the majority never develop a psychotic disorder? • Could telling someone they are at risk for psychosis activate internalized stigma that has been associated with increased emotional distress, social withdrawal, non-engagement in treatment, and suicide risk in CHR youth? • Within the context of a larger study of stigma in CHR, we compared emotional responses to the CHR concept assessed before and after clinical feedback by study clinicians. • Some participants had been told of their risk prior to study entry; others had not

Sustaining entrepreneurial business: a complexity perspective on processes that produce emergent practice

This article examines the management practices in an entrepreneurial small firm which sustain the business. Using a longitudinal qualitative case study, four general processes are identified (experimentation, reflexivity, organising and sensing), that together provide a mechanism to sustain the enterprise. The analysis draws on concepts from entrepreneurship and complexity science. We suggest that an entrepreneur’s awareness of the role of these parallel processes will facilitate their approaches to sustaining and developing enterprises. We also suggest that these processes operate in parallel at multiple levels, including the self, the business and inter-firm networks. This finding contributes to a general theory of entrepreneurship. A number of areas for further research are discussed arising from this result