This study investigates the forces that contributed to severe shortages in personal protective equipment in the US during the COVID-19 crisis. Problems from a dysfunctional costing model in hospital ...operating systems were magnified by a very large demand shock triggered by acute need in healthcare and panicked marketplace behavior that depleted domestic PPE inventories. The lack of effective action on the part of the federal government to maintain and distribute domestic inventories, as well as severe disruptions to the PPE global supply chain, amplified the problem. Analysis of trade data shows that the US is the world's largest importer of face masks, eye protection, and medical gloves, making it highly vulnerable to disruptions in exports of medical supplies. We conclude that market prices are not appropriate mechanisms for rationing inputs to health because health is a public good. Removing the profit motive for purchasing PPE in hospital costing models, strengthening government capacity to maintain and distribute stockpiles, developing and enforcing regulations, and pursuing strategic industrial policy to reduce US dependence on imported PPE will help to better protect healthcare workers with adequate supplies of PPE.
•Market failure and government failure contributed to PPE shortage during COVID-19•Dysfunctional hospital budgeting models disincentivize adequate inventories of PPE•Federal government failed to maintain and distribute domestic inventories of PPE•Pursue strategic industrial policy to reduce US dependence on PPE supply chain•Market prices are inappropriate mechanisms for rationing inputs to health, like PPE
Labonté proposes that health equity and environmental sustainability may be best obtained through a care economy. Because a care economy plays a key role in Labonté's formulation, its position in the ...capitalist political economy, the work it entails, and the workers who do it all merit further reflection. I aim to complement Labonté's editorial by elaborating on care economies and the work of social reproduction. The existing care economy is a structural part of capitalism that largely generates and sustains inequities, reinforcing Labonté's argument that transformation is needed. Transformation could, and should, change the perceived value, status, and material rewards of work in the care economy. I then touch on the policy tools Labonté describes, highlighting how they connect to my broader point: that the care economy is currently an integral, but devalued part of capitalism. For a transformation to take place, raising perceived value, status, and material rewards of caring work and the people who do it must be an explicit policy goal.
Familiarizing yourself with resources and checking in with your students on basic needs can provide you with more information on how to best support them and improve learning conditions. When ...students lack a sense of belonging, they experience additional challenges with academic performance and retention and are more at risk for stress, anxiety, and depression 26,27. Because of the cultural differences described in Rule 3, FLI STEM students can experience additional barriers to feeling like they belong. At the individual level, FLI students may have responsibilities within their families or communities to provide emotional support and advocacy, language brokering, financial support, physical care, life advice, and heavy sibling/parent caretaking 30,31. Consider offering affordable alternatives such as an open-exchange STEM library or putting a statement about basic needs in your syllabus to show your commitment to supporting FLI student learning 9 (see 9 for more examples of strategies for faculty).
Nurses are a critical part of healthcare delivery systems, especially in under-resourced environments. Compared to other female-dominated professions in South Africa, nurses are securely employed and ...relatively well-paid. However, they are often drawn from complex, poor communities where they are responsible for many dependents and must accommodate community and family expectations of financial, health, and other forms of support.
The aim of the study was to explore public hospital-employed, black women nurses' lived experiences to better understand their stressors and consider interventions that may reduce psychological distress.
In 2015, we conducted semi-structured life history interviews with 71 nurses in Johannesburg. Using grounded theory and social network mapping, we trace complex, interrelated stressors and networks of familial dependency.
Every participant experienced high levels of stress. Nurses described daily lives of chronic distress, with extreme pressures on their incomes, time, and resources. Much of the pressure on nurses comes from familial and partner dependency, both in absolute number of dependents and intensity, and related financial obligations and debt. Dependency is a function of social and cultural norms which assign women primary responsibility for unpaid work, yet nurses characterized their efforts as unsustainable and anxiety-inducing; their pay and paid work schedules made meeting that responsibility virtually impossible.
The structure of the nursing occupation contributes to stress outside the workplace, while the structure of nurses' households contributes to stress and emotional exhaustion. The integrated nature of their chronic stress suggests that occupationally-oriented interventions are unlikely to adequately address it. To fully alleviate chronic stress, the gender norms that place responsibility for unpaid work on nurses with already full-time employment need to shift. A better understanding of the extensive networks dependent on nurses should inform interventions designed to improve their wellbeing. Assistance addressing childcare, mental health, and financial planning may be especially useful.
Beckwith-Wiedemann syndrome (BWS) is the most common epigenetic overgrowth and cancer predisposition disorder. Due to both varying molecular defects involving chromosome 11p15 and tissue mosaicism, ...patients can present with a variety of clinical features, leading to the newly defined Beckwith-Wiedemann spectrum (BWSp). The BWSp can be further divided into three subsets of patients: those presenting with classic features, those presenting with isolated lateralized overgrowth (ILO) and those not fitting into the previous two categories, termed atypical BWSp. Previous reports of patients with BWS have focused on those with the more recognizable, classic features, and limited information is available on those who fit into the atypical and ILO categories. Here, we present the first cohort of patients recruited across the entire BWSp, describe clinical features and molecular diagnostic characteristics, and provide insight into practical diagnosis and management recommendations that we have gained from this cohort.
This paper presents findings from a qualitative study on teachers' negotiation of professional identity through talk with colleagues at an urban, public, Midwestern school in the United States. The ...purpose of the research was to identify discourse strategies the teachers used to negotiate local significances for their professional identities. Analysis and findings demonstrate that the teachers made and recognised identity bids to accomplish the professional identity of teacher as learner, using a range of discourse strategies, including two genres of reflective talk. Implications for our understanding of teachers as knowledge-producers and how this can inform teacher education and education policy are considered.
Improved in vitro systems for predicting drug-induced toxicity are needed in the pharmaceutical and biotechnology industries to decrease late-stage drug attrition. One unmet need is an early screen ...for cardiotoxicity, which accounts for about one third of safety-based withdrawn pharmaceuticals. Herein, the first published report of a high-throughput functional assay employing a monolayer of beating human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is described, detailing a model that accurately detects drug-induced cardiac abnormalities. Using 96-well plates with interdigitated electrode arrays that assess impedance, the rhythmic, synchronous contractions of the iPSC-CMs were detected. Treatment of the iPSC-CMs with 28 different compounds with known cardiac effects resulted in compound-specific changes in the beat rate and/or the amplitude of the impedance measurement. Changes in impedance for the compounds tested were comparable with the results from a related technology, electric field potential assessment obtained from microelectrode arrays. Using the results from the set of compounds, an index of drug-induced arrhythmias was calculated, enabling the determination of a drug's proarrhythmic potential. This system of interrogating human cardiac function in vitro opens new opportunities for predicting cardiac toxicity and studying cardiac biology.
Some types of collagens, including transmembrane MACIT collagens and C. elegans cuticle collagens, are N-terminally cleaved at a dibasic site that resembles the consensus for furin or other ...proprotein convertases of the subtilisin/kexin (PCSK) family. Such cleavage may release transmembrane collagens from the plasma membrane and affect extracellular matrix assembly or structure. However, the functional consequences of such cleavage are unclear and evidence for the role of specific PCSKs is lacking. Here, we used endogenous collagen fusions to fluorescent proteins to visualize the secretion and assembly of the first collagen-based cuticle in C. elegans and then tested the role of the PCSK BLI-4 in these processes. Unexpectedly, we found that cuticle collagens SQT-3 and DPY-17 are secreted into the extraembryonic space several hours before cuticle matrix assembly. Furthermore, this early secretion depends on BLI-4/PCSK; in bli-4 and cleavage-site mutants, SQT-3 and DPY-17 are not efficiently secreted and instead form large intracellular puncta. Their later assembly into cuticle matrix is reduced but not entirely blocked. These data reveal a role for collagen N-terminal processing in intracellular trafficking and the control of matrix assembly in vivo. Our observations also prompt a revision of the classic model for C. elegans cuticle matrix assembly and the pre-cuticle-to-cuticle transition, suggesting that cuticle layer assembly proceeds via a series of regulated steps and not simply by sequential secretion and deposition.
Abstract
Elucidation of predictive fluidic biochemical markers to detect and monitor chemical-induced neurodegeneration has been a major challenge due to a lack of understanding of molecular ...mechanisms driving altered neuronal morphology and function, as well as poor sensitivity in methods to quantify low-level biomarkers in bodily fluids. Here, we evaluated 5 neurotoxicants (acetaminophen negative control, bisindolylmaleimide-1, colchicine, doxorubicin, paclitaxel, and rotenone) in human-induced pluripotent stem cell-derived neurons to profile secreted microRNAs (miRNAs) at early and late stages of decline in neuronal cell morphology and viability. Based on evaluation of these morphological (neurite outgrowth parameters) and viability (adenosine triphosphate) changes, 2 concentrations of each chemical were selected for analysis in a human 754 miRNA panel: a low concentration with no/minimal effect on cell viability but a significant decrease in neurite outgrowth, and a high concentration with a significant decrease in both endpoints. A total of 39 miRNAs demonstrated significant changes (fold-change ≥ 1.5 or ≤ 0.67, p value < .01) with at least 1 exposure. Further analyses of targets modulated by these miRNAs revealed 38 key messenger RNA targets with roles in neurological dysfunctions, and identified transforming growth factor-beta (TGF-β) signaling as a commonly enriched pathway. Of the 39 miRNAs, 5 miRNAs, 3 downregulated (miR-20a, miR-30b, and miR-30d) and 3 upregulated (miR-1243 and miR-1305), correlated well with morphological changes induced by multiple neurotoxicants and were notable based on their relationship to various neurodegenerative conditions and/or key pathways, such as TGF-β signaling. These datasets reveal miRNA candidates that warrant further evaluation as potential safety biomarkers of chemical-induced neurodegeneration.
Zona Pellucida domain (ZP) proteins are critical components of the body's external-most protective layers, apical extracellular matrices (aECMs). Although their loss or dysfunction is associated with ...many diseases, it remains unclear how ZP proteins assemble in aECMs. Current models suggest that ZP proteins polymerize via their ZPn subdomains, while ZPc subdomains modulate ZPn behavior. Using the model organism C. elegans, we investigated the aECM assembly of one ZP protein, LET-653, which shapes several tubes. Contrary to prevailing models, we find that LET-653 localizes and functions via its ZPc domain. Furthermore, we show that ZPc domain function requires cleavage at the LET-653 C-terminus, likely in part to relieve inhibition of the ZPc by the ZPn domain, but also to promote some other aspect of ZPc domain function. In vitro, the ZPc, but not ZPn, domain bound crystalline aggregates. These data offer a new model for ZP function whereby the ZPc domain is primarily responsible for matrix incorporation and tissue shaping.
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