Bisphenol A (BPA) is an endocrine disrupting environmental contaminant used in a wide variety of products, and BPA metabolites are found in almost everyone's urine, suggesting widespread exposure ...from multiple sources. Regulatory agencies estimate that virtually all BPA exposure is from food and beverage packaging. However, free BPA is applied to the outer layer of thermal receipt paper present in very high (∼20 mg BPA/g paper) quantities as a print developer. Not taken into account when considering thermal paper as a source of BPA exposure is that some commonly used hand sanitizers, as well as other skin care products, contain mixtures of dermal penetration enhancing chemicals that can increase by up to 100 fold the dermal absorption of lipophilic compounds such as BPA. We found that when men and women held thermal receipt paper immediately after using a hand sanitizer with penetration enhancing chemicals, significant free BPA was transferred to their hands and then to French fries that were eaten, and the combination of dermal and oral BPA absorption led to a rapid and dramatic average maximum increase (Cmax) in unconjugated (bioactive) BPA of ∼7 ng/mL in serum and ∼20 µg total BPA/g creatinine in urine within 90 min. The default method used by regulatory agencies to test for hazards posed by chemicals is intra-gastric gavage. For BPA this approach results in less than 1% of the administered dose being bioavailable in blood. It also ignores dermal absorption as well as sublingual absorption in the mouth that both bypass first-pass liver metabolism. The elevated levels of BPA that we observed due to holding thermal paper after using a product containing dermal penetration enhancing chemicals have been related to an increased risk for a wide range of developmental abnormalities as well as diseases in adults.
To update the 2000 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSF).
The Update Committee completed a review and analysis of pertinent data ...published from 1999 through September 2005. Guided by the 1996 ASCO clinical outcomes criteria, the Update Committee formulated recommendations based on improvements in survival, quality of life, toxicity reduction and cost-effectiveness.
The 2005 Update Committee agreed unanimously that reduction in febrile neutropenia (FN) is an important clinical outcome that justifies the use of CSFs, regardless of impact on other factors, when the risk of FN is approximately 20% and no other equally effective regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of FN in patients who are at high risk based on age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. CSF use allows a modest to moderate increase in dose-density and/or dose-intensity of chemotherapy regimens. Dose-dense regimens should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Prophylactic CSF for patients with diffuse aggressive lymphoma aged 65 years and older treated with curative chemotherapy (CHOP or more aggressive regimens) should be given to reduce the incidence of FN and infections. Current recommendations for the management of patients exposed to lethal doses of total body radiotherapy, but not doses high enough to lead to certain death due to injury to other organs, includes the prompt administration of CSF or pegylated G-CSF.
Land‐based enhanced rock weathering (ERW) is a biogeochemical carbon dioxide removal (CDR) strategy aiming to accelerate natural geological processes of carbon sequestration through application of ...crushed silicate rocks, such as basalt, to croplands and forested landscapes. However, the efficacy of the approach when undertaken with basalt, and its potential co‐benefits for agriculture, require experimental and field evaluation. Here we report that amending a UK clay‐loam agricultural soil with a high loading (10 kg/m2) of relatively coarse‐grained crushed basalt significantly increased the yield (21 ± 9.4%, SE) of the important C4 cereal Sorghum bicolor under controlled environmental conditions, without accumulation of potentially toxic trace elements in the seeds. Yield increases resulted from the basalt treatment after 120 days without P‐ and K‐fertilizer addition. Shoot silicon concentrations also increased significantly (26 ± 5.4%, SE), with potential benefits for crop resistance to biotic and abiotic stress. Elemental budgets indicate substantial release of base cations important for inorganic carbon removal and their accumulation mainly in the soil exchangeable pools. Geochemical reactive transport modelling, constrained by elemental budgets, indicated CO2 sequestration rates of 2–4 t CO2/ha, 1–5 years after a single application of basaltic rock dust, including via newly formed soil carbonate minerals whose long‐term fate requires assessment through field trials. This represents an approximately fourfold increase in carbon capture compared to control plant–soil systems without basalt. Our results build support for ERW deployment as a CDR technique compatible with spreading basalt powder on acidic loamy soils common across millions of hectares of western European and North American agriculture.
Amending a UK clay‐loam agricultural soil with a high loading (10 kg/m2) of relatively coarse‐grained crushed basalt significantly increased the yield (21 ± 9.4%) of the important C4 cereal Sorghum bicolor under controlled environmental conditions, without accumulation of potentially toxic trace elements in the seeds, and CO2 sequestration potential.
Minnesota populations of Diabrotica virgifera virgifera LeConte, the western corn rootworm, surviving Cry3Bb1-expressing corn in the field and western corn rootworm populations assumed to be ...susceptible to all Bt proteins were evaluated for susceptibility to Cry3Bb1, mCry3A, eCry3.1Ab, and Cry34/35Ab1 in diet assays and three different plant-based assays. Rootworm populations originating from Cry3Bb1 fields and that consistently experienced greater than expected damage had increased survival and larval growth compared to control populations assayed on Cry3Bb1 as well as mCry3a and eCry3.1Ab. Cross resistance was documented between Cry3Bb1 and both mCry3A and eCry3.1Ab as single toxins. Despite very high resistance ratios in some comparisons, cross resistance was not complete and also varied with the population being evaluated, the trait measured, and the susceptible rootworm population used for comparison. Regardless of resistance and cross resistance, all proteins, even Cry3Bb1, retained some efficacy in terms of either reducing rootworm larval growth, protecting plants from damage, or both, for all rootworm populations evaluated. For one Cry3Bb1-selected population, a resistance ratio of 9.1-fold was found to Cry34/35Ab1 when evaluating EC50 values relative to a susceptible control population; however, resistance to Cry34/35Ab1 was not evident in all assays in this population. The United States Environmental Protection Agency recently suggested eliminating diet assays as part of the Bt resistance monitoring process. However, given the variability of responses of western corn rootworm populations to different proteins in different assays, both plant and diet assays are needed as options for detecting and fully characterizing resistance.
Burgeoning consumer interest in organically produced foods has made organic farming one of the fastest growing segments of agriculture. This growth has not been supported adequately by rigorous ...research to address challenges such as arthropod pest management. The research that has been conducted, however, is complemented by research in aspects of conventional agriculture that may have applicability in organic systems, as well as by research in underpinning fields such as applied ecology. This article synthesizes the available literature in relation to a conceptual model of arthropod pest management strategies suitable for organic systems. The present work uses the four phases of the model to review the strategies in an agroecological context and provides a synthesis of the factors that influence the success of each phase. Rather than constituting a fringe science, pest management research for organic systems draws on cutting edge science in fields such as landscape and chemical ecology and has a bright future.
The adipocyte-derived secretory factor adiponectin promotes insulin sensitivity, decreases inflammation and promotes cell survival. No unifying mechanism has yet explained how adiponectin can exert ...such a variety of beneficial systemic effects. Here, we show that adiponectin potently stimulates a ceramidase activity associated with its two receptors, AdipoR1 and AdipoR2, and enhances ceramide catabolism and formation of its antiapoptotic metabolite--sphingosine-1-phosphate (S1P)--independently of AMP-dependent kinase (AMPK). Using models of inducible apoptosis in pancreatic beta cells and cardiomyocytes, we show that transgenic overproduction of adiponectin decreases caspase-8-mediated death, whereas genetic ablation of adiponectin enhances apoptosis in vivo through a sphingolipid-mediated pathway. Ceramidase activity is impaired in cells lacking both adiponectin receptor isoforms, leading to elevated ceramide levels and enhanced susceptibility to palmitate-induced cell death. Combined, our observations suggest a unifying mechanism of action for the beneficial systemic effects exerted by adiponectin, with sphingolipid metabolism as its core upstream signaling component.
Enhanced silicate rock weathering (ERW), deployable with croplands, has potential use for atmospheric carbon dioxide (CO2) removal (CDR), which is now necessary to mitigate anthropogenic climate ...change1. ERW also has possible co-benefits for improved food and soil security, and reduced ocean acidification2-4. Here we use an integrated performance modelling approach to make an initial techno-economic assessment for 2050, quantifying how CDR potential and costs vary among nations in relation to business-as-usual energy policies and policies consistent with limiting future warming to 2 degrees Celsius5. China, India, the USA and Brazil have great potential to help achieve average global CDR goals of 0.5 to 2 gigatonnes of carbon dioxide (CO2) per year with extraction costs of approximately US$80-180 per tonne of CO2. These goals and costs are robust, regardless of future energy policies. Deployment within existing croplands offers opportunities to align agriculture and climate policy. However, success will depend upon overcoming political and social inertia to develop regulatory and incentive frameworks. We discuss the challenges and opportunities of ERW deployment, including the potential for excess industrial silicate materials (basalt mine overburden, concrete, and iron and steel slag) to obviate the need for new mining, as well as uncertainties in soil weathering rates and land-ocean transfer of weathered products.
Leadership is a valuable skill that can be taught in school, and which may have benefits within and beyond the classroom. Learning to Lead (L2L) is a student-led, primary school-based leadership ...program whereby older 'peer leaders' deliver a fundamental movement skills (FMS) program to younger 'peers' within their own school.
The aims of the study are to determine the efficacy of a peer-led FMS intervention on: (i) peer leaders' (aged 10 to 12 years) leadership effectiveness (primary outcome), leadership self-efficacy, well-being, and time on-task in the classroom; (ii) peers' (aged 8 to 10 years) physical activity levels, actual and perceived FMS competency, cardiorespiratory fitness, muscular power, and executive functioning; and (iii) teachers' (referred to as 'school champions') work-related stress and well-being.
L2L will be evaluated using a two-arm parallel group cluster randomised controlled trial. Twenty schools located within a two-hour drive of the University of Newcastle, Australia will be recruited. We will recruit 80 students (40 peer leaders and 40 peers) from each school (N = 1,600). L2L will be implemented in three phases: Phase 1 -school champions' training via a professional learning workshop; Phase 2 -school champions' delivery of leadership lessons to the peer leaders; and Phase 3 -peer leaders' delivery of the FMS program to their younger peers. The FMS program, consisting of 12 x 30-minute lessons, will be delivered over the course of one school term (10 weeks). Study outcomes will be assessed at baseline (between mid-March to June, Terms 1 and 2), intervention end (mid-August to September, Term 3), and follow-up (November to mid-December, Term 4. This trial was prospectively registered on the Australian New Zealand Clinical Trials Registry (ANZCTR); registration number: ACTRN12621000376842.
The failure of metabolic tissues to appropriately respond to insulin ("insulin resistance") is an early marker in the pathogenesis of type 2 diabetes. Protein phosphorylation is central to the ...adipocyte insulin response, but how adipocyte signaling networks are dysregulated upon insulin resistance is unknown. Here we employ phosphoproteomics to delineate insulin signal transduction in adipocyte cells and adipose tissue. Across a range of insults causing insulin resistance, we observe a marked rewiring of the insulin signaling network. This includes both attenuated insulin-responsive phosphorylation, and the emergence of phosphorylation uniquely insulin-regulated in insulin resistance. Identifying dysregulated phosphosites common to multiple insults reveals subnetworks containing non-canonical regulators of insulin action, such as MARK2/3, and causal drivers of insulin resistance. The presence of several bona fide GSK3 substrates among these phosphosites led us to establish a pipeline for identifying context-specific kinase substrates, revealing widespread dysregulation of GSK3 signaling. Pharmacological inhibition of GSK3 partially reverses insulin resistance in cells and tissue explants. These data highlight that insulin resistance is a multi-nodal signaling defect that includes dysregulated MARK2/3 and GSK3 activity.
The aim of our systematic review and meta-analysis was to quantitatively synthesise the effects of school-based peer-led interventions on leaders' academic, psychosocial, behavioural, and physical ...outcomes. Eligible studies were those that: (i) evaluated a school-based peer-led intervention using an experimental or quasi-experimental study design, (ii) included an age-matched control or comparison group, and (iii) evaluated the impact of the intervention on one or more leader outcomes. Medline, Sportdiscus, Psychinfo, Embase, and Scopus online databases were searched on the 24th of October, 2022 which yielded 13,572 results, with 31 included in the narrative synthesis and 12 in the meta-analysis. We found large positive effects for leaders' attitudes toward bullying (d = 1.02), small-to-medium positive effects for leaders' literacy (d = 0.39), and small positive effects for leaders' self-esteem (d = 0.18). There were mixed findings for behavioural outcomes and null effects for physical outcomes. Notable limitations of this research are the inclusion of a relatively small number of studies, and high heterogeneity in those included. Our findings have the potential to inform educational practice, but also highlight the need for further research examining the mechanisms that might account for the observed effects. Our systematic review was prospectively registered with PROSPERO (CRD42021273129).
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