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A daring life : a biography of Eudora Welty
\"Mississippi author Eudora Welty--winner of the Pulitzer Prize and the National Book Award and the first living writer to be published in the Library of America series--mentored many of today's greatest fiction writers. This fascinating woman observed and wrote brilliantly throughout the majority of the twentieth century (1909-2001). Her life reflects a century of rapid change and is closely entwined with many events that mark our recent history. This biography tells Welty's story, beginning with her parents and their important influence on her reading and writing life. The chapters that follow focus on her education and her most important teachers as well as her life during the Depression and how her new career, just getting started, was interrupted by World War II. Throughout she shows independence and courage in her writing, especially during the turbulent civil rights period of the 1950s and 1960s. After years of care-giving and the deaths of all her immediate family members, Welty persevered, wrote acclaimed short stories, and won the Pulitzer Prize in 1973 for The Optimist's Daughter. Her popularity soared in the 1980s after she delivered the three William E. Massey Lectures to standing-room-only crowds at Harvard. The lectures were later published as One Writer's Beginnings and became a New York Times bestseller. This biography will introduce readers of all ages to one of the most significant writers of the past century, a prolific author who comprehends and transcends her Mississippi roots to create short stories, novels, and nonfiction that will endure for all time\"--Provided by publisher.
Book
What is the impact of mental health-related stigma on help-seeking? A systematic review of quantitative and qualitative studies
Individuals often avoid or delay seeking professional help for mental health problems. Stigma may be a key deterrent to help-seeking but this has not been reviewed systematically. Our systematic review addressed the overarching question: What is the impact of mental health-related stigma on help-seeking for mental health problems? Subquestions were: (a) What is the size and direction of any association between stigma and help-seeking? (b) To what extent is stigma identified as a barrier to help-seeking? (c) What processes underlie the relationship between stigma and help-seeking? (d) Are there population groups for which stigma disproportionately deters help-seeking?
Five electronic databases were searched from 1980 to 2011 and references of reviews checked. A meta-synthesis of quantitative and qualitative studies, comprising three parallel narrative syntheses and subgroup analyses, was conducted.
The review identified 144 studies with 90,189 participants meeting inclusion criteria. The median association between stigma and help-seeking was d = - 0.27, with internalized and treatment stigma being most often associated with reduced help-seeking. Stigma was the fourth highest ranked barrier to help-seeking, with disclosure concerns the most commonly reported stigma barrier. A detailed conceptual model was derived that describes the processes contributing to, and counteracting, the deterrent effect of stigma on help-seeking. Ethnic minorities, youth, men and those in military and health professions were disproportionately deterred by stigma.
Stigma has a small- to moderate-sized negative effect on help-seeking. Review findings can be used to help inform the design of interventions to increase help-seeking.
Journal Article
Born of illusion
\"Set in 1920s New York City, this is the story of budding magician Anna Van Housen, who has spent her whole life playing sidekick to her faux-medium mother--and trying to hide the fact the she actually possesses the very abilities her mother fakes\"-- Provided by publisher.
Book
Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension
Aldosterone synthase controls the synthesis of aldosterone and has been a pharmacologic target for the treatment of hypertension for several decades. Selective inhibition of aldosterone synthase is essential but difficult to achieve because cortisol synthesis is catalyzed by another enzyme that shares 93% sequence similarity with aldosterone synthase. In preclinical and phase 1 studies, baxdrostat had 100:1 selectivity for enzyme inhibition, and baxdrostat at several dose levels reduced plasma aldosterone levels but not cortisol levels.
In this multicenter, placebo-controlled trial, we randomly assigned patients who had treatment-resistant hypertension, with blood pressure of 130/80 mm Hg or higher, and who were receiving stable doses of at least three antihypertensive agents, including a diuretic, to receive baxdrostat (0.5 mg, 1 mg, or 2 mg) once daily for 12 weeks or placebo. The primary end point was the change in systolic blood pressure from baseline to week 12 in each baxdrostat group as compared with the placebo group.
A total of 248 patients completed the trial. Dose-dependent changes in systolic blood pressure of -20.3 mm Hg, -17.5 mm Hg, -12.1 mm Hg, and -9.4 mm Hg were observed in the 2-mg, 1-mg, 0.5-mg, and placebo groups, respectively. The difference in the change in systolic blood pressure between the 2-mg group and the placebo group was -11.0 mm Hg (95% confidence interval [CI], -16.4 to -5.5; P<0.001), and the difference in this change between the 1-mg group and the placebo group was -8.1 mm Hg (95% CI, -13.5 to -2.8; P = 0.003). No deaths occurred during the trial, no serious adverse events were attributed by the investigators to baxdrostat, and there were no instances of adrenocortical insufficiency. Baxdrostat-related increases in the potassium level to 6.0 mmol per liter or greater occurred in 2 patients, but these increases did not recur after withdrawal and reinitiation of the drug.
Patients with treatment-resistant hypertension who received baxdrostat had dose-related reductions in blood pressure. (Funded by CinCor Pharma; BrigHTN ClinicalTrials.gov number, NCT04519658.).
Journal Article
Born of deception
Moving to London in the 1920s to join a prestigious European vaudeville tour and reunite with her boyfriend Cole, budding illusionist Anna must harness her special powers and navigate the underworld of magic before her murderous enemies catch up with her.
Book
Advances in therapeutic peptides targeting G protein-coupled receptors
Dysregulation of peptide-activated pathways causes a range of diseases, fostering the discovery and clinical development of peptide drugs. Many endogenous peptides activate G protein-coupled receptors (GPCRs) — nearly 50 GPCR peptide drugs have been approved to date, most of them for metabolic disease or oncology, and more than 10 potentially first-in-class peptide therapeutics are in the pipeline. The majority of existing peptide therapeutics are agonists, which reflects the currently dominant strategy of modifying the endogenous peptide sequence of ligands for peptide-binding GPCRs. Increasingly, novel strategies are being employed to develop both agonists and antagonists, to both introduce chemical novelty and improve drug-like properties. Pharmacodynamic improvements are evolving to allow biasing ligands to activate specific downstream signalling pathways, in order to optimize efficacy and reduce side effects. In pharmacokinetics, modifications that increase plasma half-life have been revolutionary. Here, we discuss the current status of the peptide drugs targeting GPCRs, with a focus on evolving strategies to improve pharmacokinetic and pharmacodynamic properties.Many G protein-coupled receptors (GPCRs) have endogenous peptide agonists, and modifying the sequence of these peptides has led to some successful therapeutics. In this Review, Davenport and colleagues discuss strategies to generate effective GPCR-targeted peptide therapeutics by introducing chemical novelty, extending plasma half-life, improving a therapeutic’s drug-like properties or generating biased ligands. These approaches could overcome some of the challenges in developing peptide therapeutics.
Journal Article
Microbial modulation of cardiovascular disease
Although diet has long been known to contribute to the pathogenesis of cardiovascular disease (CVD), research over the past decade has revealed an unexpected interplay between nutrient intake, gut microbial metabolism and the host to modify the risk of developing CVD. Microbial-associated molecular patterns are sensed by host pattern recognition receptors and have been suggested to drive CVD pathogenesis. In addition, the host microbiota produces various metabolites, such as trimethylamine-N-oxide, short-chain fatty acids and secondary bile acids, that affect CVD pathogenesis. These recent advances support the notion that targeting the interactions between the host and microorganisms may hold promise for the prevention or treatment of CVD. In this Review, we summarize our current knowledge of the gut microbial mechanisms that drive CVD, with special emphasis on therapeutic interventions, and we highlight the need to establish causal links between microbial pathways and CVD pathogenesis.
Journal Article
Velvet undercover
\"A World War I era spy novel about a bright British girl who is sent undercover into the heart of enemy territory to rescue Britain's most valuable (and secret) spy\"-- Provided by publisher.
Book
Sulfoxaflor exposure reduces bumblebee reproductive success
Intensive agriculture currently relies on pesticides to maximize crop yield
1
,
2
. Neonicotinoids are the most widely used insecticides globally
3
, but increasing evidence of negative impacts on important pollinators
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–
9
and other non-target organisms
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has led to legislative reassessment and created demand for the development of alternative products. Sulfoximine-based insecticides are the most likely successor
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, and are either licensed for use or under consideration for licensing in several worldwide markets
3
, including within the European Union
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, where certain neonicotinoids (imidacloprid, clothianidin and thiamethoxam) are now banned from agricultural use outside of permanent greenhouse structures. There is an urgent need to pre-emptively evaluate the potential sub-lethal effects of sulfoximine-based pesticides on pollinators
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, because such effects are rarely detected by standard ecotoxicological assessments, but can have major impacts at larger ecological scales
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–
15
. Here we show that chronic exposure to the sulfoximine-based insecticide sulfoxaflor, at dosages consistent with potential post-spray field exposure, has severe sub-lethal effects on bumblebee (
Bombus terrestris
) colonies. Field-based colonies that were exposed to sulfoxaflor during the early growth phase produced significantly fewer workers than unexposed controls, and ultimately produced fewer reproductive offspring. Differences between the life-history trajectories of treated and control colonies first became apparent when individuals exposed as larvae began to emerge, suggesting that direct or indirect effects on a small cohort may have cumulative long-term consequences for colony fitness. Our results caution against the use of sulfoximines as a direct replacement for neonicotinoids. To avoid continuing cycles of novel pesticide release and removal, with concomitant impacts on the environment, a broad evidence base needs to be assessed prior to the development of policy and regulation.
Chronic exposure to sulfoxaflor (a sulfoximine-based insecticide) has severe sub-lethal effects on bumblebee (
Bombus terrestris
) colonies; exposed colonies produced fewer workers and fewer reproductive offspring than unexposed control colonies.
Journal Article