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1.
PLoS One ; 19(7): e0305634, 2024.
Article in English | MEDLINE | ID: mdl-38959187

ABSTRACT

In this study, we examine the association between Big Five personality traits and cigar or cigarette smoking in a sample of 9,918 older adults across 11 European countries derived from the Survey of Health, Ageing and Retirement in Europe (SHARE) dataset. We find significant associations between several traits and smoking groups. Smoking was associated with lower scores on Conscientiousness and Agreeableness and higher Extraversion scores. In addition, cigar smokers exhibit lower Neuroticism and higher Openness compared to both cigarette smokers and non-smokers. These findings suggest that both personality traits are antecedents of smoking behavior, offering implications for targeted public health interventions and social policies aimed at combating the global tobacco epidemic.


Subject(s)
Cigarette Smoking , Personality , Humans , Male , Female , Aged , Middle Aged , Cigarette Smoking/psychology , Cigarette Smoking/epidemiology , Europe/epidemiology , Tobacco Products , Smoking/psychology , Smoking/epidemiology
3.
PNAS Nexus ; 3(6): pgae191, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38864006

ABSTRACT

Generative artificial intelligence (AI) has the potential to both exacerbate and ameliorate existing socioeconomic inequalities. In this article, we provide a state-of-the-art interdisciplinary overview of the potential impacts of generative AI on (mis)information and three information-intensive domains: work, education, and healthcare. Our goal is to highlight how generative AI could worsen existing inequalities while illuminating how AI may help mitigate pervasive social problems. In the information domain, generative AI can democratize content creation and access but may dramatically expand the production and proliferation of misinformation. In the workplace, it can boost productivity and create new jobs, but the benefits will likely be distributed unevenly. In education, it offers personalized learning, but may widen the digital divide. In healthcare, it might improve diagnostics and accessibility, but could deepen pre-existing inequalities. In each section, we cover a specific topic, evaluate existing research, identify critical gaps, and recommend research directions, including explicit trade-offs that complicate the derivation of a priori hypotheses. We conclude with a section highlighting the role of policymaking to maximize generative AI's potential to reduce inequalities while mitigating its harmful effects. We discuss strengths and weaknesses of existing policy frameworks in the European Union, the United States, and the United Kingdom, observing that each fails to fully confront the socioeconomic challenges we have identified. We propose several concrete policies that could promote shared prosperity through the advancement of generative AI. This article emphasizes the need for interdisciplinary collaborations to understand and address the complex challenges of generative AI.

4.
Nurs Philos ; 25(3): e12486, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38853432

ABSTRACT

Nurses working in outreach capacities frequently encounter disaffiliated or 'hard to reach' populations, such as those experiencing homelessness, those who use substances, and those with mental health concerns. Despite best efforts, nurses regularly fail to find meaningful engagement with these populations. Mobilizing the work of Deleuze and Guattari, this paper will critically examine conventional outreach nursing practices as rooted in the royal science of psychiatry, which many 'survivors' of psychiatric interventions reject. The field of Mad Studies offers an understanding of patient resistance to outreach nursing interventions. Delueze and Guattari's concepts of packs and sorcerers provide a framework to envision alternative nursing practices as a form of resistance and creativity, where new alliances may be formed outside the coercive confines of traditional practices. In response to patient resistance, outreach nurses themselves must assemble packs and engage in acts of sorcery.


Subject(s)
Nurses , Humans , Nurses/psychology
5.
Biotechnol Bioeng ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711222

ABSTRACT

In the past decade, new approaches to the discovery and development of vaccines have transformed the field. Advances during the COVID-19 pandemic allowed the production of billions of vaccine doses per year using novel platforms such as messenger RNA and viral vectors. Improvements in the analytical toolbox, equipment, and bioprocess technology have made it possible to achieve both unprecedented speed in vaccine development and scale of vaccine manufacturing. Macromolecular structure-function characterization technologies, combined with improved modeling and data analysis, enable quantitative evaluation of vaccine formulations at single-particle resolution and guided design of vaccine drug substances and drug products. These advances play a major role in precise assessment of critical quality attributes of vaccines delivered by newer platforms. Innovations in label-free and immunoassay technologies aid in the characterization of antigenic sites and the development of robust in vitro potency assays. These methods, along with molecular techniques such as next-generation sequencing, will accelerate characterization and release of vaccines delivered by all platforms. Process analytical technologies for real-time monitoring and optimization of process steps enable the implementation of quality-by-design principles and faster release of vaccine products. In the next decade, the field of vaccine discovery and development will continue to advance, bringing together new technologies, methods, and platforms to improve human health.

6.
J Am Chem Soc ; 146(18): 12836-12849, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38683943

ABSTRACT

The biological properties of two water-soluble organic cations based on polypyridyl structures commonly used as ligands for photoactive transition metal complexes designed to interact with biomolecules are investigated. A cytotoxicity screen employing a small panel of cell lines reveals that both cations show cytotoxicity toward cancer cells but show reduced cytotoxicity to noncancerous HEK293 cells with the more extended system being notably more active. Although it is not a singlet oxygen sensitizer, the more active cation also displayed enhanced potency on irradiation with visible light, making it active at nanomolar concentrations. Using the intrinsic luminescence of the cations, their cellular uptake was investigated in more detail, revealing that the active compound is more readily internalized than its less lipophilic analogue. Colocalization studies with established cell probes reveal that the active cation predominantly localizes within lysosomes and that irradiation leads to the disruption of mitochondrial structure and function. Stimulated emission depletion (STED) nanoscopy and transmission electron microscopy (TEM) imaging reveal that treatment results in distinct lysosomal swelling and extensive cellular vacuolization. Further imaging-based studies confirm that treatment with the active cation induces lysosomal membrane permeabilization, which triggers lysosome-dependent cell-death due to both necrosis and caspase-dependent apoptosis. A preliminary toxicity screen in the Galleria melonella animal model was carried out on both cations and revealed no detectable toxicity up to concentrations of 80 mg/kg. Taken together, these studies indicate that this class of synthetically easy-to-access photoactive compounds offers potential as novel therapeutic leads.


Subject(s)
Antineoplastic Agents , Cations , Phenazines , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Cations/chemistry , Cations/pharmacology , Phenazines/chemistry , Phenazines/pharmacology , Lysosomes/metabolism , Lysosomes/drug effects , HEK293 Cells , Apoptosis/drug effects , Drug Screening Assays, Antitumor , Cell Line, Tumor , Animals , Theranostic Nanomedicine , Molecular Structure
7.
Dalton Trans ; 53(17): 7282-7291, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38466178

ABSTRACT

Transition metal complexes containing the qtpy ligand (2':4,4'':4',4'''-quaterpyridyl) are known to be DNA intercalators or minor groove binders. In this study, new tricationic iridium(III) complexes of qtpy are reported. Both [Ir(bpy)2(qtpy)]3+1 and [Ir(phen)2(qtpy)]3+2 display good water solubility as chloride salts. The complexes possess high-energy excited states, which are quenched in the presence of duplex DNA and even by the mononucleotides guanosine monophosphate and adenosine monophosphate. Further studies reveal that although the complexes bind to quadruplex DNA, they display a preference for duplex structures, which are bound with an order of magnitude higher affinities than their isostructural dicationic RuII-analogues. Detailed molecular dynamics simulations confirm that the complexes are groove binders through the insertion of, predominantly, the qtpy ligand into the minor groove. Photoirradiation of 1 in the presence of plasmid DNA confirms that this class of complexes can function as synthetic photonucleases by cleaving DNA.


Subject(s)
Coordination Complexes , DNA , Iridium , Iridium/chemistry , DNA/chemistry , DNA/metabolism , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , DNA Cleavage , Molecular Dynamics Simulation , Ligands , Molecular Structure
8.
Curr Psychol ; 43(9): 7997-8007, 2024.
Article in English | MEDLINE | ID: mdl-38549732

ABSTRACT

This cross-cultural study compared judgments of moral wrongness for physical and emotional harm with varying combinations of in-group vs. out-group agents and victims across six countries: the United States of America (N = 937), the United Kingdom (N = 995), Romania (N = 782), Brazil (N = 856), South Korea (N = 1776), and China (N = 1008). Consistent with our hypothesis we found evidence of an insider agent effect, where moral violations committed by outsider agents are generally considered more morally wrong than the same violations done by insider agents. We also found support for an insider victim effect where moral violations that were committed against an insider victim generally were seen as more morally wrong than when the same violations were committed against an outsider, and this effect held across all countries. These findings provide evidence that the insider versus outsider status of agents and victims does affect moral judgments. However, the interactions of these identities with collectivism, psychological closeness, and type of harm (emotional or physical) are more complex than what is suggested by previous literature. Supplementary information: The online version contains supplementary material available at 10.1007/s12144-023-04986-3.

9.
PLoS One ; 19(2): e0298293, 2024.
Article in English | MEDLINE | ID: mdl-38358977

ABSTRACT

Could judgments about others' moral character be changed under group pressure produced by human and virtual agents? In Study 1 (N = 103), participants first judged targets' moral character privately and two weeks later in the presence of real humans. Analysis of how many times participants changed their private moral judgments under group pressure showed that moral conformity occurred, on average, 43% of the time. In Study 2 (N = 138), we extended this using Virtual Reality, where group pressure was produced either by avatars allegedly controlled by humans or AI. While replicating the effect of moral conformity (at 28% of the time), we find that the moral conformity for the human and AI-controlled avatars did not differ. Our results suggest that human and nonhuman groups shape moral character judgments in both the physical and virtual worlds, shedding new light on the potential social consequences of moral conformity in the modern digital world.


Subject(s)
Judgment , Social Behavior , Humans , Morals , Interpersonal Relations , Character , Social Conformity
10.
ACS Chem Biol ; 19(3): 753-762, 2024 03 15.
Article in English | MEDLINE | ID: mdl-38412264

ABSTRACT

Activating transcription factor 3 (ATF3) is an activation transcription factor/cyclic adenosine monophosphate (cAMP) responsive element-binding (CREB) protein family member. It is recognized as an important regulator of cancer progression by repressing expression of key inflammatory factors such as interferon-γ and chemokine (C-C motif) ligand 4 (CCL4). Here, we describe a novel library screening approach that probes individual leucine zipper components before combining them to search exponentially larger sequence spaces not normally accessible to intracellular screening. To do so, we employ two individual semirational library design approaches and screen using a protein-fragment complementation assay (PCA). First, a 248,832-member library explored 12 amino acid positions at all five a positions to identify those that provided improved binding, with all e/g positions fixed as Q, placing selection pressure onto the library options provided. Next, a 59,049-member library probed all ten e/g positions with 3 options. Similarly, during e/g library screening, a positions were locked into a generically bindable sequence pattern (AIAIA), weakly favoring leucine zipper formation, while placing selection pressure onto e/g options provided. The combined a/e/g library represents ∼14.7 billion members, with the resulting peptide, ATF3W_aeg, binding ATF3 with high affinity (Tm = 60 °C; Kd = 151 nM) while strongly disfavoring homodimerization. Moreover, ATF3W_aeg is notably improved over component PCA hits, with target specificity found to be driven predominantly by electrostatic interactions. The combined a/e/g exponential library screening approach provides a robust, accelerated platform for exploring larger peptide libraries, toward derivation of potent yet selective antagonists that avoid homoassociation to provide new insight into rational peptide design.


Subject(s)
Activating Transcription Factor 3 , Peptide Library , Activating Transcription Factor 3/metabolism , Cyclic AMP Response Element-Binding Protein/chemistry , Cyclic AMP Response Element-Binding Protein/genetics , Cyclic AMP Response Element-Binding Protein/metabolism , Gene Expression Regulation , Peptides/metabolism
11.
CVIR Endovasc ; 7(1): 1, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38170369
12.
J Forensic Nurs ; 20(2): 80-86, 2024.
Article in English | MEDLINE | ID: mdl-38271478

ABSTRACT

ABSTRACT: Online radicalization has gained considerable attention in the media and in academia. Much attention has shifted to so-called "homegrown terrorists." Mental health concerns of those who display signs of online radicalization are identified as a potential contributing factor to this process. Although it seems both tempting to attribute mental health concerns, attempts to "make sense" of schizoposting (a bizarre and often violent form of online engagement) via conventional "clinical" analysis prove insufficient. This article offers a critical analysis of an extremely disturbing (online) phenomenon through the radical poststructuralist scholarship of late French philosophers, Deleuze and Guattari. Given that schizoposting and those individuals who engage in this behavior have yet to receive any attention in the nursing and health-related literature, it is critical that future research aims to better understand this population, such that appropriate interventions may be proposed.


Subject(s)
Internet , Humans , Terrorism
13.
Nurs Inq ; 31(1): e12558, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37127936

ABSTRACT

Recovery is a model of care in (forensic) mental health settings across Western nations that aims to move past the paternalistic and punitive models of institutional care of the 20th century and toward more patient-centered approaches. But as we argue in this paper, the recovery-oriented services that evolved out of the early stages of this liberating movement signaled a shift in nursing practices that cannot be viewed only as improvements. In effect, as "recovery" nursing practices became more established, more codified, and more institutional(ized), a stasis developed. Recovery had been reterritorialized. The purpose of this paper is to examine some of the threads of recovery, from its early days of antipsychiatry activism to its codification into mental health-including forensic mental health-institutions through the lens of poststructuralist philosophers Gilles Deleuze and Felix Guattari. We believe that Deleuze and Guattari's scholarship provides the necessary, albeit uncomfortable, framework for this critical examination. From a conceptualization of recovery as an assemblage, we critically examine how we can go about creating something new, caught in a tension between stasis and change.


Subject(s)
Mental Health Services , Humans
14.
Nurs Philos ; 25(1): e12440, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37070337

ABSTRACT

Nurses working in correctional and forensic mental health settings face unique challenges in the provision of care to patients within custodial settings. The subjectivities of both patients and nurses are subject to the power relations, discourses and abjection encountered within these practice milieus. Using a poststructuralist approach using the work of Foucault, Kristeva, and Deleuze and Guattari, this paper explores how both patient and nurse subjectivities are produced within the carceral logic of this apparatus of capture. Recognizing that subjectivities are fluid and dynamic, and capable of change, Deleuze and Guattari's concept of deterritorialization will illustrate opportunities for resistance, where nurses can begin to practice outside the dominant carceral logic (and restrictions) of the system.


Subject(s)
Mental Health , Nursing , Humans
15.
Psychol Sci ; 34(12): 1309-1321, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37955906

ABSTRACT

Global access to resources like vaccines is key for containing the spread of infectious diseases. However, wealthy countries often pursue nationalistic policies, stockpiling doses rather than redistributing them globally. One possible motivation behind vaccine nationalism is a belief among policymakers that citizens will mistrust leaders who prioritize global needs over domestic protection. In seven experiments (total N = 4,215 adults), we demonstrate that such concerns are misplaced: Nationally representative samples across multiple countries with large vaccine surpluses (Australia, Canada, United Kingdom, and United States) trusted redistributive leaders more than nationalistic leaders-even the more nationalistic participants. This preference generalized across different diseases and manifested in both self-reported and behavioral measures of trust. Professional civil servants, however, had the opposite intuition and predicted higher trust in nationalistic leaders, and a nonexpert sample also failed to predict higher trust in redistributive leaders. We discuss how policymakers' inaccurate intuitions might originate from overestimating others' self-interest.


Subject(s)
Trust , Vaccines , Adult , Humans , Australia , Intuition , Motivation , Vaccination
16.
PLoS One ; 18(7): e0288491, 2023.
Article in English | MEDLINE | ID: mdl-37440506

ABSTRACT

Phthalate plasticizers are incorporated into plastics to make them soft and malleable, but are known to leach out of the final product into their surroundings with potential detrimental effects to human and ecological health. The replacement of widely-used phthalate plasticizers, such as di-ethylhexyl phthalate (DEHP), that are of known toxicity, by the commercially-available alternative Tris(2-ethylhexyl) tri-mellitate (TOTM) is increasing. Additionally, several newly designed "green" plasticizers, including di-heptyl succinate (DHPS) and di-octyl succinate (DOS) have been identified as potential replacements. However, the impact of plasticizer exposure from medical devices on patient recovery is unknown and, moreover, the safety of TOTM, DHPS, and DOS is not well established in the context of patient recovery. To study the direct effect of clinically based chemical exposures, we exposed C57bl/6 N male and female mice to DEHP, TOTM, DOS, and DHPS during recovery from cardiac surgery and assessed survival, cardiac structure and function, immune cell infiltration into the cardiac wound and activation of the NLRP3 inflammasome. Male, but not female, mice treated in vivo with DEHP and TOTM had greater cardiac dilation, reduced cardiac function, increased infiltration of neutrophils, monocytes, and macrophages and increased expression of inflammasome receptors and effectors, thereby suggesting impaired recovery in exposed mice. In contrast, no impact was detected in female mice and male mice exposed to DOS and DHPS. To examine the direct effects in cells involved in wound healing, we treated human THP-1 macrophages with the plasticizers in vitro and found DEHP induced greater NLRP3 expression and activation. These results suggest that replacing current plasticizers with non-phthalate-based plasticizers may improve patient recovery, especially in the male population. In our assessment, DHPS is a promising possibility for a non-toxic biocompatible plasticizer.


Subject(s)
Diethylhexyl Phthalate , Myocardial Infarction , Male , Humans , Mice , Animals , Plasticizers/toxicity , Plasticizers/chemistry , Diethylhexyl Phthalate/toxicity , Succinic Acid , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Succinates , Mice, Inbred Strains
17.
Chemosphere ; 335: 139121, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37271465

ABSTRACT

3-Nitro-1,2,4-triazol-5-one (NTO) is an ingredient of new safer-to-handle military insensitive munitions formulations. NTO can be microbially reduced to 3-amino-1,2,4-triazol-5-one (ATO) under anaerobic conditions if an electron donor is available. Conversely, ATO can undergo aerobic biodegradation. Previously, our research group developed an anaerobic enrichment culture that reduces NTO to ATO. A second culture could aerobically mineralize ATO. This study aimed to combine anaerobic/aerobic conditions within a down-flow perlite/soil column for simultaneous NTO reduction and ATO oxidation. Acetate biostimulation was investigated to promote oxygen depletion and create anaerobic micro-niches for NTO reduction, whereas perlite increased soil porosity and oxygen convection, allowing ATO oxidation. Two columns packed with a perlite/soil mixture (70:30, wet wt.%) or 100% perlite were operated aerobically and inoculated with the NTO- and ATO-degrading cultures. Initially, the influent consisted of ∼280 µM ATO, and after 30 days, the feeding was switched to ∼260 µM NTO and ∼250 µM acetate. By progressively increasing acetate from 250 to 4000 µM, the NTO removal gradually improved in both columns. The perlite/soil column reached a 100% NTO removal after 4000 µM acetate was supplemented. Additionally, there was no ATO accumulation, and inorganic nitrogen was produced, indicating ATO mineralization. Although NH4+ was produced following ATO oxidation, most nitrogen was recovered as NO3- likely via nitrification reactions. Microbial community analysis revealed that phylotypes hosted in the enrichment cultures specialized in NTO reduction (e.g., Geobacter) and ATO oxidation (e.g., Hydrogenophaga, Ramlibacter, Terrimonas, and Pseudomonas) were established in the columns. Besides, the predominant genera (Azohydromonas, Zoogloea, and Azospirillum) are linked to nitrogen cycling by performing nitrogen fixation, NO3- reduction, and nitroaromatics degradation. This study applied a bulking agent (perlite) and acetate biostimulation to achieve simultaneous NTO reduction and ATO oxidation in a single column. Such a strategy can assist with real-world applications of NTO and ATO biodegradation mechanisms.


Subject(s)
Nitro Compounds , Soil , Biodegradation, Environmental , Nitro Compounds/metabolism , Nitrogen/metabolism
19.
J Forensic Nurs ; 19(2): 115-121, 2023.
Article in English | MEDLINE | ID: mdl-37205618

ABSTRACT

ABSTRACT: The Canadian federal prison population is increasingly aging within institutions that were never intended or designed to meet the complex medical and mental health needs of older incarcerated persons. Increasing numbers of incarcerated persons are "aging in place," and many are dying within federal correctional institutions. Persons convicted of sexual offenses comprise a large-and growing-proportion of this aging population. The Correctional Investigator Canada has recently called for an expansion of access to compassionate release for the aging federal prison population, yet little progress has been made. In this article, we explore the significant challenges faced by the aging population in federal institutions, including insufficient access to appropriate care, challenges in application for compassionate release, and how questions of risk may affect the potential for community transfer. Questions of risk overshadow decisions on early release of incarcerated persons, especially those convicted of sexual offenses. Nurses play a central role in the provision of care to aging incarcerated persons and in advocacy for better access to services when a patient's needs cannot be met within the institution. This article presents a call to action for forensic nurses in Canada (and beyond) to advocate for both improved services within federal correctional institutions and for expedited access to compassionate release of aging incarcerated persons, especially those nearing end of life. The significant disparity in access to health care for aging incarcerated persons compared with their nonincarcerated counterparts represents a significant concern.


Subject(s)
Prisoners , Prisons , Humans , Aged , Canada , Independent Living , Aging
20.
Stem Cells Dev ; 32(13-14): 387-397, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37166357

ABSTRACT

Transplantation of human induced pluripotent stem cell-derived dopaminergic (iPSC-DA) neurons is a promising therapeutic strategy for Parkinson's disease (PD). To assess optimal cell characteristics and reproducibility, we evaluated the efficacy of iPSC-DA neuron precursors from two individuals with sporadic PD by transplantation into a hemiparkinsonian rat model after differentiation for either 18 (d18) or 25 days (d25). We found similar graft size and dopamine (DA) neuron content in both groups, but only the d18 cells resulted in recovery of motor impairments. In contrast, we report that d25 grafts survived equally as well and produced grafts rich in tyrosine hydroxylase-positive neurons, but were incapable of alleviating any motor deficits. We identified the mechanism of action as the extent of neurite outgrowth into the host brain, with d18 grafts supporting significantly more neurite outgrowth than nonfunctional d25 grafts. RNAseq analysis of the cell preparation suggests that graft efficacy may be enhanced by repression of differentiation-associated genes by REST, defining the optimal predifferentiation state for transplantation. This study demonstrates for the first time that DA neuron grafts can survive well in vivo while completely lacking the capacity to induce recovery from motor dysfunction. In contrast to other recent studies, we demonstrate that neurite outgrowth is the key factor determining graft efficacy and our gene expression profiling revealed characteristics of the cells that may predict their efficacy. These data have implication for the generation of DA neuron grafts for clinical application.


Subject(s)
Dopaminergic Neurons , Induced Pluripotent Stem Cells , Humans , Rats , Animals , Transcriptome , Reproducibility of Results , Cell Differentiation/physiology , Neuronal Outgrowth
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