The wellbeing pandemic: Outline of a contested terrain and a proposed research agenda.

Wellbeing has emerged as a central, if not defining, feature of contemporary social life. Yet, despite its global significance spanning the political, social and economic spectrum, there is a remarkable lack of agreement regarding the conceptualization, definition or operationalisation of wellbeing nor any clear evidence of its success as an instrument of policy. This essay explores the contested terrain of wellbeing by examining the concept in relation to emerging politics, complexities and contradictions. More specifically, the essay: (1) briefly describes the historical origins and development of wellbeing; (2) discusses how it has been reconceptualised within the context of neoliberalism; and, (3) outlines a research agenda offering three ways to investigate wellbeing including: (a) as a wicked problem; (b) as part of the process of "wellbeing washing" within state and other institutional structures and policies; and, (c) in relation to alternative futures, which might encourage us to reimagine or jettison the term altogether.

The Global Business of Sport in a Brave New World: Conceptualising a Framework for Alternative Futures.

In July 1991, Sports Illustrated published a special issue featuring two articles that prognosticated about what sport would look like 10 years later. As the world entered the 21st century, Sports Illustrated writers, Oscar Johnson and Ron Fimrite, offered their visions of sport in the year 2001. Their analysis highlighted how a range of economic, social and technological changes in society would impact on how sport is structured, produced and consumed, but also offered insights into the future of the major professional sport leagues in North America. It has been 30 years since they publicised their views and, while technology continues to impact sport, the Covid-19 pandemic has forced the world to pause and to consider a range of deep, soul-searching questions about the nature of society, including sport. Against this background, we consider the opportunities and challenges for sport in the 21st century. The paper is divided into three sections including: (1) a reflection on the meaning, value and significance of sport including its privileged position in society, or what we refer to as "sporting exceptionalism"; (2) a brief overview of a case study that illustrates the challenges facing the global business of sport; and, (3) a framework for conceptualising alternative futures in the global business of sport, drawing on examples from women's sport.

A precise, reproducible method for measuring ultrasound probe slice thickness using a Gammex 403 phantom.

A precise, reproducible method for measuring ultrasound probe slice thickness has been developed for linear array ultrasound probes. The method used a custom built jig to draw the probe along the surface of a Gammex 403 phantom, with the image plane parallel to the filaments within the phantom. Still images at 0.5 mm intervals are saved for post-processing using in-house software. Slice thickness measurements with a precision of 0.1 mm are obtained. The method was shown to give reproducible estimates of probe slice thickness at several depths to within 0.4 mm during repeat tests. The method was able to provide information about the slice thickness of different sections of the probe face. It is expected that the method can quantify changes in probe performance due to lens wear or replacement over time that may elude both in-plane and in-air reverberation-based tests. A total of 18 linear probes were tested across eight centres, including six specialist vascular ultrasound centres.

Phytonutrients Differentially Stimulate NAD(P)H:Quinone Oxidoreductase, Inhibit Proliferation, and Trigger Mitotic Catastrophe in Hepa1c1c7 Cells.

Phytonutrients have rapidly emerged as natural food chemicals possessing multifaceted biological actions that may support beneficial health outcomes. Among the vast array of phytonutrients currently being studied, sulforaphane, curcumin, quercetin, and resveratrol have been frequently reported to stimulate the expression of endogenous detoxification enzymes and may thereby facilitate the neutralization of otherwise harmful environmental agents. Some of these same phytonutrients, however, have also been implicated in disrupting normal cell proliferation and hence may possess toxic properties in and of themselves. In this study, we characterize the respective minimum threshold concentrations of the aforementioned phytonutrients in Hepa1c1c7 cells that stimulate NAD(P)H: quinone oxidoreductase (NQO1), a key enzyme in the hepatic neutralization of menadione, other biological oxidants, and some environmental carcinogens. Moreover, our findings demonstrate that relatively low concentrations of either sulforaphane or curcumin significantly (P < .05) increase NQO1 protein expression and activity without triggering G2/M cell cycle arrest or mitotic catastrophe. The minimal quercetin concentration inducing NQO1, however, was 100-fold higher than that which disrupted mitosis. Also, while resveratrol modestly stimulated NQO1, the minimally effective resveratrol concentration concomitantly induced evidence of cellular apoptosis. Taken together, these findings indicate that only particular phytonutrients are likely efficacious in upregulating NQO1 activity without also leading to hepatic cytotoxicity.

Supplemental genistein, quercetin, and resveratrol intake in active duty army soldiers.

Previous reports indicate that the majority of U.S. Army soldiers consume dietary supplements (DSs) > 1 time/wk. However, these studies did not evaluate phytonutrient supplementation. A growing literature suggests inclusion of phytonutrients in DSs may pose a risk for toxicity, which could impact the performance of soldier duties, as well as long-term health and wellness. This study was conducted to assess and understand soldiers' motivations to consume phytonutrient-containing DSs, specifically genistein, quercetin, and resveratrol. The study was a cross-sectional, descriptive mixed-methods design using a survey and semistructured interviews. There were 436 soldiers stationed at Joint Base Lewis-McChord, Washington who completed the survey, from which 36 soldiers completed an interview. Overall, 34% of soldiers reported taking a single or multicomponent phytonutrient DS > 1 time/wk, from which 41 soldiers took >1 supplement/wk. Soldiers' reasons for use included unsure (54%), weight loss (12%), and other, unspecified (24%). The majority of interviewees did not consume DSs based on inclusion of genistein, quercetin, or resveratrol. The majority of soldiers, in our study, appear unable to rationalize their phytonutrient DS choices. Findings from this study illuminate the need for future research to further explore DS practices within military populations and encourage informed use of DSs.

Curcumin binds tubulin, induces mitotic catastrophe, and impedes normal endothelial cell proliferation.

Curcumin, a component of turmeric spice that imparts flavor and color to curry, is thought to possess anti-inflammatory and antioxidant properties in biological tissues. However, while such efficacies have been described in the context of carcinogenesis, the impact of curcumin on normal cell cycle regulation is poorly understood. Here, we provide evidence of curcumin toxicity in proliferating bovine aortic endothelial cells, at concentrations relevant to the diet and below those previously reported in cancer models. Upon confirming curcumin's ability to upregulate hemeoxygenase-1 in a dose-dependent fashion, we found the minimally efficacious curcumin concentration to also inhibit endothelial cell DNA synthesis. Moreover, curcumin concentrations below the minimum 2 µM threshold required to induce hemeoxygenase-1 bound tubulin protein in vitro and triggered hallmark evidence of mitotic catastrophe in vivo. Concentrations as low as 0.1 µM curcumin led to disproportionate DNA segregation, karyorrhexis, and micronucleation in proliferating endothelial cells. While suggesting a mechanism by which physiological curcumin concentrations inhibit cell cycle progression, these findings describe heretofore unappreciated curcumin toxicity with potential implications for endothelial growth, development, and tissue healing.

Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization.

Sulforaphane (SUL), an isothiocyanate derived from broccoli and other cruciferous vegetables, is known to induce phase II detoxification enzymes, disrupt cancer cell microtubule polymerization, and trigger cell cycle arrest in breast and colon cancer cells. Here, we provide the first evidence that SUL also acts to inhibit angiogenesis via suppression of endothelial cell proliferation. Bovine aortic endothelial (BAE) cells were exposed to concentrations of up to 15 microM SUL prior to cell cycle analysis and mitotic index quantification. Within 24 h, 15 microM SUL clearly induced G(2)/M accumulation and pre-metaphase arrest in BAE cells. Moreover, immunofluorescence tubulin staining indicated that this same SUL concentration was efficacious in not only disrupting mitotic progression, but also in perturbing normal polymerization of mitotic (and cytoplasmic) microtubules. Furthermore, daily administration of SUL (100 nmol/day, i.v. for 7 days) to female Balb/c mice bearing VEGF-impregnated Matrigel plugs strongly and significantly (P<0.05) suppressed angiogenesis progression as measured by hemoglobin concentration. Taken together, these findings suggest that the endothelial cell population is a novel target of SUL action both in vitro and in vivo. This mechanism of SUL-induced endothelial microtubule disruption and early mitotic arrest may further discern a potential role of SUL as a chemopreventive agent.

Quercetin inhibits eNOS, microtubule polymerization, and mitotic progression in bovine aortic endothelial cells.

Quercetin (QRN), one of the most abundant flavonoids in the human diet, is a known antioxidant and inhibitor of cancer cell cycle progression. Here, we provide the first evidence that QRN inhibits angiogenesis via a mechanism involving both suppression of endothelial nitric oxide synthase (eNOS) and early M-phase cell cycle arrest. Bovine aortic endothelial (BAE) cells were exposed to doses of up to 100 micromol/L QRN and assayed for eNOS activity and phosphorylation status. Phosphorylation of eNOS at Ser 617 (bovine sequence) is thought to occur in response to Akt stimulation and to be required for eNOS activity. Together with basal eNOS activity, eNOS phosphorylation at Ser 617 and Akt Ser 473 phosphorylation were dose dependently and concomitantly suppressed by QRN within 30 min. Furthermore, although the significant (P < 0.05) inhibitory effect of a single 100 micromol/L QRN dose on eNOS activity was overcome within approximately 24 h, chronic QRN exposures (24-48 h) led to early M-phase arrest and disruption of mitotic microtubule polymerization. In vivo, QRN administered i.p. to female Balb/C mice bearing both syngeneic mammary tumors and Matrigel implants suppressed angiogenesis as measured by endothelial cell immunohistochemistry and hemoglobin concentration. Taken together, these findings suggest a dual mechanism by which QRN suppresses endothelial cell proliferation, both acutely via inhibition of eNOS Ser 617 phosphorylation, and chronically via perturbation of mitotic microtubule polymerization. This novel mechanism of QRN in endothelial cells may in part explain its inhibitory action on angiogenesis and further discern a potential role of QRN as a chemopreventive agent.

Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization.

Sulforaphane (SUL), an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes, inhibit chemically induced mammary tumors in rodents, and more recently, to induce cell cycle arrest and apoptosis in colon cancer cells. In the present study, we demonstrate that SUL also acts to inhibit proliferation of MCF-7 adenocarcinoma cells from the human breast. Treatment of synchronized MCF-7 cells with 15 micromol/L SUL resulted in significant (P < 0.05) G(2)/M cell cycle arrest (167% of control) and elevated cyclin B1 protein (175% of control) within 24 h. Moreover, 15 micromol/L SUL significantly (P < 0.05) induced phosphorylation of histone H1 (167% of control), blocked cells in early mitosis ( approximately 10-fold increase over control), and disrupted polymerization of mitotic microtubules in vivo. Subsequent exposure of purified bovine brain tubulin to relatively high doses of SUL significantly (P < 0.05) inhibited both tubulin polymerization rate (51% of control) and total tubulin polymerization (78% of control) in vitro. Additionally, polymerization of purified tubulin exposed to isothiocyanate-containing analogs of SUL was similarly inhibited. Taken together, these findings indicate that SUL has mammary cancer suppressive actions involving mitotic cell cycle arrest and suggest a mechanism linked to the disruption of normal tubulin polymerization and/or more subtle effects on microtubule dynamics.

Sulforaphane: a naturally occurring mammary carcinoma mitotic inhibitor, which disrupts tubulin polymerization.

Sulforaphane (SUL), an isothiocyanate found in broccoli and other cruciferous vegetables, has been shown to induce phase II detoxification enzymes, inhibit chemically induced mammary tumors in rats, and more recently to induce cell cycle arrest and apoptosis in cancer cells of the colon. Here, we provide evidence that SUL also acts as a breast cancer anti-proliferative agent. The BALB/c mouse mammary carcinoma cell line F3II was treated with SUL at concentrations up to 15 microM and examined for markers of cell cycle arrest and apoptosis. Treatment of asynchronous F3II cells with 15 microM SUL resulted in G2/M cell cycle arrest, elevated p34cdc2 (cdc2) kinase activity, Bcl-2 down-regulation, evidence of caspase activation, and aggregation of condensed nuclear chromatin. Subsequent exposure of synchronized cells to 15 microM SUL resulted in elevated numbers of prophase/prometaphase mitotic figures, indicating cell cycle progression beyond G2 and arrest early within mitosis. Moreover, cells treated with 15 microM SUL displayed aberrant mitotic spindles, and higher doses of SUL inhibited tubulin polymerization in vitro. In addition, BALB/c mice injected s.c. with F3II cells and subsequently injected daily i.v. with SUL (15 nmol/day for 13 days) developed significantly smaller tumors (approximately 60% less in mass) than vehicle-treated controls. Western blot analysis of tumor proteins demonstrated significantly (P<0.05) reduced PCNA and elevated PARP fragmentation in samples from animals dosed with SUL. Taken together, these results indicate that SUL has mammary cancer suppressive actions both in cell culture and in the whole animal. Inhibition of mammary carcinogenesis appears in part to involve perturbation of mitotic microtubules and early M-phase block associated with cdc2 kinase activation, indicating that cells arrest prior to metaphase exit.