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This paper aims to develop a better understanding of what proponents of natural childbirth mean by 'natural.' Using a biosocial approach to birth that posits that all birth is both social and natural, the paper investigates how proponents represent the relationship between nature and society. The study asks about what kinds of nature-society relationships are expressed in proponents' representations of natural childbirth. The study examines how natural childbirth is represented by proponents in popular non-fictional English language books written for pregnant women. Claims in these books are not taken as reality, but are analyzed as ideas about nature-society relations. The central finding is that these authors simultaneously emphasize the naturalness of birth and showcase three types of social practices that they describe as being integral to natural childbirth: (1) activity during birth, (2) preparation before birth, and (3) social support, both in an individual and in a broader socio-cultural sense. At least for these authors, it is these social practices that allow natural childbirth to be natural. These findings on the social nature of natural childbirth challenge current social science scholarship, in which natural childbirth is characterized as an essentializing and nostalgic attempt to return to nature. [ABSTRACT FROM AUTHOR]

Cholera toxin (CT) travels as an intact AB(5) protein toxin from the cell surface to the endoplasmic reticulum (ER) of an intoxicated cell. In the ER, the catalytic A1 subunit dissociates from the rest of the toxin. Translocation of CTA1 from the ER to the cytosol is then facilitated by the quality control mechanism of ER-associated degradation (ERAD). Thermal instability in the isolated CTA1 subunit generates an unfolded toxin conformation that acts as the trigger for ERAD-mediated translocation to the cytosol. In this work, we show by circular dichroism and fluorescence spectroscopy that exposure to 4-phenylbutyric acid (PBA) inhibited the thermal unfolding of CTA1. This, in turn, blocked the ER-to-cytosol export of CTA1 and productive intoxication of either cultured cells or rat ileal loops. In cell culture studies PBA did not affect CT trafficking to the ER, CTA1 dissociation from the holotoxin, or functioning of the ERAD system. PBA is currently used as a therapeutic agent to treat urea cycle disorders. Our data suggest PBA could also be used in a new application to prevent or possibly treat cholera.

AB toxins such as ricin and cholera toxin (CT) consist of an enzymatic A domain and a receptor-binding B domain. After endocytosis of the surface-bound toxin, both ricin and CT are transported by vesicle carriers to the endoplasmic reticulum (ER). The A subunit then dissociates from its holotoxin, unfolds, and crosses the ER membrane to reach its cytosolic target. Since protein unfolding at physiological temperature and neutral pH allows the dissociated A chain to attain a translocation-competent state for export to the cytosol, the underlying regulatory mechanisms of toxin unfolding are of paramount biological interest. Here we report a biophysical analysis of the effects of anionic phospholipid membranes and two chemical chaperones, 4-phenylbutyric acid (PBA) and glycerol, on the thermal stabilities and the toxic potencies of ricin toxin A chain (RTA) and CT A1 chain (CTA1). Phospholipid vesicles that mimic the ER membrane dramatically decreased the thermal stability of RTA but not CTA1. PBA and glycerol both inhibited the thermal disordering of RTA, but only glycerol could reverse the destabilizing effect of anionic phospholipids. In contrast, PBA was able to increase the thermal stability of CTA1 in the presence of anionic phospholipids. PBA inhibits cellular intoxication by CT but not ricin, which is explained by its ability to stabilize CTA1 and its inability to reverse the destabilizing effect of membranes on RTA. Our data highlight the toxin-specific intracellular events underlying ER-to-cytosol translocation of the toxin A chain and identify a potential means to supplement the long-term stabilization of toxin vaccines.

Patients with glycogen storage disease type Ia (GSD-Ia) develop renal disease of unknown etiology despite intensive dietary therapies. This renal disease shares many clinical and pathological similarities to diabetic nephropathy. We studied the expression of angiotensinogen, angiotensin type 1 receptor, transforming growth factor-β1, and connective tissue growth factor in mice with GSD-Ia and found them to be elevated compared to controls. While increased renal expression of angiotensinogen was evident in 2-week-old mice with GSD-Ia, the renal expression of transforming growth factor-β and connective tissue growth factor did not increase for another week; consistent with upregulation of these factors by angiotensin II. The expression of fibronectin and collagens I, III, and IV was also elevated in the kidneys of mice with GSD-Ia, compared to controls. Renal fibrosis was characterized by a marked increase in the synthesis and deposition of extracellular matrix proteins in the renal cortex and histological abnormalities including tubular basement membrane thickening, tubular atrophy, tubular dilation, and multifocal interstitial fibrosis. Our results suggest that activation of the angiotensin system has an important role in the pathophysiology of renal disease in patients with GSD-Ia.Kidney International (2008) 73, 716–723; doi:10.1038/sj.ki.5002718; published online 12 December 2007 [ABSTRACT FROM AUTHOR]

Reducing low-density lipoprotein cholesterol (LDL-C) levels is crucial to the prevention of atherosclerotic cardiovascular disease (ASCVD). However, many patients, especially those at very high ASCVD risk or with familial hypercholesterolemia (FH), do not achieve target LDL-C levels with statin monotherapy. The underutilization of novel lipid-lowering therapies (LLT) globally may be due to cost concerns or therapeutic inertia. Emerging approaches have the potential to lower LDL-C and reduce ASCVD risk further, in addition to offering alternatives for statin-intolerant patients. Shifting the treatment paradigm towards initial combination therapy and utilizing novel LLT strategies can complement existing treatments. This review discusses innovative approaches including combination therapies involving statins and agents like ezetimibe, bempedoic acid, cholesterol ester transfer protein (CETP) inhibitors as well as strategies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and angiopoietin-like protein 3 (ANGPTL3) inhibition. Advances in nucleic acid-based therapies and gene editing are innovative approaches that will improve patient compliance and adherence. These strategies demonstrate significant LDL-C reductions and improved cardiovascular outcomes, offering potential for optimal LDL-C control and reduced ASCVD risk. By addressing the limitations of statin monotherapy, these approaches provide new management options for elevated LDL-C levels.

Natural history, loosely defined as the observational study of organisms in the habitats where they occur, is recognized at the roots of ecology. Although the centrality of natural history in ecology has shifted over time, natural history is currently in resurgence: many again consider it to be the foundation of ecological and evolutionary inquiry and advocate the value of organism-centered approaches to address contemporary ecological challenges. Educators identify natural history as the foundational entryway into the practice of ecology, for example in the Ecological Society of America's Four-Dimensional Ecology Education (4DEE) framework. A strong natural history foundation can help generate testable hypotheses to refine mechanistic understanding of the drivers regulating species distributions and abundances and to inform restoration and conservation efforts. Given the resurgence of natural history as the foundation for ecological knowledge and practice, it is important to recognize that natural history has a long history of racism that has impacted ecological thought and priorities. This history shapes not only who conducts ecological science but also foundational ecological concepts. For example, natural history's emphasis on pristine nature untouched by humans disregards or appropriates stewardship and knowledge of most of the world's population. Because of the legacy of chattel slavery, this exclusion is particularly strong for people of African descent. This exclusion narrows ecological inquiry, limits the capacity to find solutions to ecological problems, and risks interventions that perpetuate the relation between eugenics, ecological knowledge, and natural systems. If ecology is to become an inclusive, responsive, and resilient discipline, this knowledge gap must be addressed. We here present the colonial and racist underpinnings of natural history and offer strategies to expand inclusion in the study of nature. Natural history was steeped in racism, providing a hierarchy of cultures and a taxonomy of races. Complementing growing interest in traditional and Indigenous ecological knowledge, we focus on Black ecological knowledge, for example in the study of "maroon ecologies." Addressing the racist history of natural history is necessary for removing structural and racist barriers to diverse participation and expanding ecological knowledge bases in service of better and more just science., (© 2022 The Authors. Ecological Applications published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

Background: Keloid formation following trauma or surgery is common among darkly pigmented individuals. Since lipoprotein(a) [Lp(a)] has been postulated to have a putative role in wound healing, and also mediates atherosclerotic cardiovascular disease, it was assessed whether Lp(a), its associated oxidized phospholipids and other oxidation-specific biomarkers were associated with keloid formation., Methods: This case-control study included darkly pigmented individuals of African ancestry, 100 with keloid scarring and 100 non-keloid controls. The lipid panel, hsCRP, Lp(a), oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB), IgG and IgM apoB-immune complexes and IgG and IgM autoantibodies to a malondialdehyde mimotope (MDA-mimotope) were measured. Immunohistochemistry of keloid specimens was performed for both Lp(a) and OxPL staining., Results: Cases and controls were well matched for age, sex and lipid profile. Mean Lp(a) (57.8 vs. 44.2 mg/dL; P = 0.01, OxPL-apoB 17.4 vs. 15.7 nmol/L; P = 0.009) and IgG and IgM apoB-immune complexes and IgG and IgM MDA-mimotope levels were significantly higher in keloid cases. Keloid tissue stained strongly for OxPL., Conclusion: Darkly pigmented individuals of African ancestry with keloids have higher plasma levels of Lp(a), OxPL-apoB and oxidation-specific epitopes. The commonality of excessive wound healing in keloids and chronic complications from coronary revascularization suggests avenues of investigation to define a common mechanism driven by Lp(a) and the innate response to oxidized lipids., (© 2022. The Author(s).)

Manual stretchers cause more injuries than hydraulic stretchers in workers who transport patients., Objective: To evaluate the impact of introducing motorized stretchers on transporter injuries and resultant workers' compensation costs., Methods: The number of transporters who sustained injuries related to stretcher manipulation, and associated workers' compensation costs, before and after the introduction of motorized stretchers, was determined. The Wilcoxon Rank Sum test was used to examine costs and lost and restricted workdays., Results: The number of injuries and restricted work days decreased after motorized stretchers were introduced. Transporters incurred less lost work days (median 24.5 vs 7 days, P = 0.050)., Conclusions: Motorized stretchers were associated with decreased injuries and lost work days., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 American College of Occupational and Environmental Medicine.)

Pharmacological allosteric agonists (calcimimetics) of the extracellular calcium-sensing receptor (CaSR) have substantial gastro-intestinal side effects and induce the expression of inflammatory markers in colon cancer cells. Here, we compared the effects of both CaSR-specific ( R enantiomers) and -unspecific ( S enantiomers) enantiomers of a calcimimetic (NPS 568) and a calcilytic (allosteric CaSR antagonists; NPS 2143) to prove that these effects are indeed mediated via the CaSR, rather than via off-target effects, e.g., on β-adrenoceptors or calcium channels, of these drugs. The unspecific S enantiomer of NPS 2143 and NPS S- 2143 was prepared using synthetic chemistry and characterized using crystallography. NPS S -2143 was then tested in HEK-293 cells stably transfected with the human CaSR (HEK-CaSR), where it did not inhibit CaSR-mediated intracellular Ca 2+ signals, as expected. HT29 colon cancer cells transfected with the CaSR were treated with both enantiomers of NPS 568 and NPS 2143 alone or in combination, and the expression of CaSR and the pro-inflammatory cytokine interleukin 8 (IL-8) was measured by RT-qPCR and ELISA. Only the CaSR-selective enantiomers of the calcimimetic NPS 568 and NPS 2143 were able to modulate CaSR and IL-8 expression. We proved that pro-inflammatory effects in colon cancer cells are indeed mediated through CaSR activation. The non-CaSR selective enantiomer NPS S- 2143 will be a valuable tool for investigations in CaSR-mediated processes.

While critics cast the Trump administration as anti-science, requiring in response vigorous defense of science, analysis of the Trump EPA reveals instead a strategy to develop deregulatory science . In its first 3 years, the Trump EPA introduced and started to implement a variety of new frameworks to remake scientific risk analysis, changing how it assesses exposures, hazards and costs of chemical harms. The article focuses on EPA frameworks associated with the Clean Air Act, Strengthening Transparency in Regulatory Science rule and Toxic Substances Control Act. The new approaches compel the agency to ignore many pathways of exposure and pivotal studies of hazards, include dose-response models that treat pollution as healthful and change how costs and benefits are calculated. Yet it justifies these frameworks in terms of evidence-based decision-making, transparency and the separation of science from politics. According to its political appointees, the Trump EPA stands for scientific integrity, because it is promulgating evidence-based approaches in risk analysis that show regulation to be neither necessary nor appropriate. This is not just rhetoric but represents an effort to engage science to delegitimize environmental regulation. There is continuity between the Trump EPA and past efforts to use science to justify regulatory rollbacks: defending science by demarcating it from non-science is just as much a strategy for deregulation as it is for regulation. A key lesson is that contesting deregulation by declaring it anti-science reflects an impasse, as deregulatory approaches then also seek to take the mantle of science. The alternative to engaging in debate over demarcation is to make explicit the values and interests shaping practices of regulatory science.

Environmental data justice (EDJ) emerges from conversations between data justice and environmental justice while identifying the limits and tensions of these lenses. Through a reflexive process of querying our entanglement in non-innocent relations, this paper develops and engages EDJ by examining how it informs the work of the Environmental Data & Governance Initiative (EDGI), a distributed, consensus-based organization that formed in response to the 2016 US presidential election. Through grassroots archiving of data sets, monitoring federal environmental and energy agency websites, and writing rapid-response reports about how federal agencies are being undermined, EDGI mobilises EDJ to challenge the 'extractive logic' of current federal environmental policy and data infrastructures. 'Extractive logic' disconnects data from provenance, privileges the matrix of domination, and whitewashes data to generate uncertainty. We use the dynamic EDJ framework to reflect on EDGI's public comment advising against the US Environmental Protection Agency's proposed rule for Transparent Science. Through EDJ, EDGI aspires to create new environmental data infrastructures and practices that are participatory and embody equitable, transparent data care.

This article addresses evidence-based practice related to adult hematopoietic stem cell transplant (HSCT) patients when admitted to the intensive care unit. Specifically, it addresses non-HSCT staff, patient, and family needs and the strategies to address those needs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this quality improvement project was to evaluate hypertension (HTN) management in patients 80 years of age and older who reside in a large, long-term care (LTC) facility., Data Source: A retrospective chart audit was conducted on 75 charts of patients 80 years of age and older and who had a diagnosis of HTN. Using the 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Expert Consensus Document on Management of Hypertension in the Elderly as a guide, blood pressure readings, significant comorbidities, and antihypertensive medication utilization were analyzed., Conclusions: LTC residents in this sample were often not treated according to expert recommendations. Specifically, analysis revealed overtreatment of uncomplicated HTN and undertreatment of those with comorbid conditions. Additionally, those with diabetes mellitus and chronic kidney disease were infrequently prescribed ace inhibitors/angiotensin receptor blockers, as recommended., Implications for Practice: Utilizing evidence-based practice (EBP) guidelines affords the best avenue for providing safe and effective treatment of HTN. While expert recommendations are available, researchers seldom recruit frail elders in LTC facilities into treatment investigations. In the absence of population-specific EBP guidelines, nurse practitioners must rely on expert opinion and diagnostic reasoning to individualize HTN treatment to this unique and vulnerable population., (©2016 American Association of Nurse Practitioners.)