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Quorum sensing (QS) is a cell-cell signaling system that enables bacteria to coordinate population density-dependent changes in behavior. This chemical communication pathway is mediated by diffusible N-acyl L-homoserine lactone signals and cytoplasmic signal-responsive LuxR-type receptors in Gram-negative bacteria. As many common pathogenic bacteria use QS to regulate virulence, there is significant interest in disrupting QS as a potential therapeutic strategy. Prior studies have implicated the natural products salicylic acid, cinnamaldehyde, and other related benzaldehyde derivatives as inhibitors of QS in the opportunistic pathogen Pseudomonas aeruginosa, yet we lack an understanding of the mechanisms by which these compounds function. Herein, we evaluate the activity of a set of benzaldehyde derivatives using heterologous reporters of the P. aeruginosa LasR and RhlR QS signal receptors. We find that most tested benzaldehyde derivatives can antagonize LasR or RhlR reporter activation at micromolar concentrations, although certain molecules also cause mild growth defects and nonspecific reporter antagonism. Notably, several compounds showed promising RhlR or LasR-specific inhibitory activities over a range of concentrations below that causing toxicity. ortho-Vanillin, a previously untested compound, was the most promising within this set. Competition experiments against the native ligands for LasR and RhlR revealed that ortho-vanillin can interact competitively with RhlR but not with LasR. Overall, these studies expand our understanding of benzaldehyde activities in the LasR and RhlR receptors and reveal potentially promising effects of ortho-vanillin as a small molecule QS modulator against RhlR. IMPORTANCE: Quorum sensing (QS) regulates many aspects of bacterial pathogenesis and has attracted much interest as a target for anti-virulence therapies over the past 30 years, for example, antagonists of the LasR and RhlR QS receptors in Pseudomonas aeruginosa. Potent and selective QS inhibitors remain relatively scarce. However, natural products have provided a bounty of chemical scaffolds with anti-QS activities, but their molecular mechanisms are poorly characterized. The current study serves to fill this void by examining the activity of an important and wide-spread class of natural product QS modulators, benzaldehydes, and related derivatives, in LasR and RhlR. We demonstrate that ortho-vanillin can act as a competitive inhibitor of RhlR, a receptor that has emerged and may supplant LasR in certain settings as a target for P. aeruginosa QS control. The results and insights provided herein will advance the design of chemical tools to study QS with improved activities and selectivities.
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The Duffy-binding protein (DBP) is a promising antigen for a malaria vaccine that would protect against clinical symptoms caused by Plasmodium vivax infection. Region II of DBP (DBP-II) contains the receptor-binding domain that engages host red blood cells, but DBP-II vaccines elicit many non-neutralizing antibodies that bind distal to the receptor-binding surface. Here, we engineered a truncated DBP-II immunogen that focuses the immune response to the receptor-binding surface. This immunogen contains the receptor-binding subdomain S1S2 and lacks the immunodominant subdomain S3. Structure-based computational design of S1S2 identified combinatorial amino acid changes that stabilized the isolated S1S2 without perturbing neutralizing epitopes. This immunogen elicited DBP-II-specific antibodies in immunized mice that were significantly enriched for blocking activity compared to the native DBP-II antigen. This generalizable design process successfully stabilized an integral core fragment of a protein and focused the immune response to desired epitopes to create a promising new antigen for malaria vaccine development.
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Anticorpos Antiprotozoários , Antígenos de Protozoários , Epitopos , Vacinas Antimaláricas , Plasmodium vivax , Proteínas de Protozoários , Receptores de Superfície Celular , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Antígenos de Protozoários/imunologia , Antígenos de Protozoários/química , Antígenos de Protozoários/genética , Plasmodium vivax/imunologia , Animais , Vacinas Antimaláricas/imunologia , Vacinas Antimaláricas/química , Epitopos/imunologia , Epitopos/química , Camundongos , Anticorpos Antiprotozoários/imunologia , Receptores de Superfície Celular/imunologia , Receptores de Superfície Celular/química , Receptores de Superfície Celular/genética , Modelos Moleculares , Malária Vivax/imunologia , Malária Vivax/prevenção & controle , Camundongos Endogâmicos BALB CRESUMO
Promoting excellence in autism intervention is arguably more urgent than ever for the field of applied behavior analysis. To fulfill this objective, autism agencies must operate from validated program systems and do so with fidelity. Program components include, but are not limited to, staff training and evaluation of clinical skills, functional personnel roles designed to promote positive outcomes for those served, and professional staff-communication-skill repertoires. Data on client outcomes must be tied to implementation of core program variables; and, contingencies between the data on client outcomes and staff performance must exist. Furthermore, these contingencies must be yoked across members of the organization to ensure a sustainable and effective program model. Finally, data on consumer satisfaction must be collected and used to evaluate program components and agency practices. Members of the Alliance for Scientific Autism Intervention have implemented key program-wide systems based upon the work of McClannahan and Krantz Journal of Applied Behavior Analysis, 26, 589-596 (1993) for decades and across various agency cultures. Data collected by six independent educational agencies on client outcomes, program implementation, and consumer feedback for a 10-year time span demonstrate the sustainability of the model and support the importance of key organizational systems and the relationship between implementation of the model and high-quality outcomes for individuals with autism.
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We demonstrate the application of proton transfer time-of-flight mass spectrometry (PTR-TOF-MS) in monitoring the kinetics of disinfectant decay in water with a sensitivity one to three orders of magnitude greater than other analytical methods. Chemical disinfection inactivates pathogens during water treatment and prevents regrowth as water is conveyed in distribution system pipes, but it also causes formation of toxic disinfection by-products. Analytical limits have hindered kinetic models, which aid in ensuring water quality and protecting public health by predicting disinfection by-products formation. PTR-TOF-MS, designed for measuring gas phase concentrations of organic compounds, was able to simultaneously monitor aqueous concentrations of five inorganic haloamines relevant to chloramine disinfection under drinking water relevant concentrations. This novel application to aqueous analytes opens a new range of applications for PTR-TOF-MS.
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In addition to extracellular amyloid plaques, intracellular neurofibrillary tau tangles, and inflammation, cognitive and emotional affect perturbations are characteristic of Alzheimer's disease (AD). The cognitive and emotional domains impaired by AD include several forms of decision making (such as intertemporal choice), blunted motivation (increased apathy), and impaired executive function (such as working memory and cognitive flexibility). However, the interaction between these domains of the mind and their supporting neurobiological substrates at prodromal stages of AD, or whether these interactions can be predictive of AD severity (individual variability), remain unclear. In this study, we employed a battery of cognitive and emotional tests in the young adult (5-7 mo) transgenic Fisher-344 AD (TgF344-AD; TgAD) rat model of AD. We also assessed whether markers of inflammation or AD-like pathology in the prelimbic cortex (PrL) of the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), or nucleus accumbens (NAc), all structures that directly support the aforementioned behaviors, were predictive of behavioral deficits. We found TgAD rats displayed maladaptive decision making, greater apathy, and impaired working memory that was indeed predicted by AD-like pathology in the relevant brain structures, even at an early age. Moreover, we report that the BLA is an early epicenter of inflammation, and notably, AD-like pathology in the PrL, BLA, and NAc was predictive of BLA inflammation. These results suggest that operant-based battery testing may be sensitive enough to determine pathology trajectories, including neuroinflammation, from early stages of AD.
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BACKGROUND: Self-efficacy, a patient-level factor, has been shown to facilitate patient engagement in treatment and optimize treatment-related outcomes in various health contexts. Research on interventions supporting hepatitis C virus (HCV) direct-acting antiviral (DAA) treatment uptake and adherence among persons who inject drugs (PWID) is needed, but whether self-efficacy factors influence DAA treatment cascade outcomes in this population has been less studied. METHODS: Using the HERO study data, we analyzed a subset of participants with any general health self-efficacy data (n=708) measured at baseline and end-of-treatment time points using a 5-items instrument (facets: 'goal setting', 'goal attainment', 'having a positive effect', 'being in control', and 'working to improve'). The cascade outcomes included DAA treatment initiation, duration, adherence, completion, and sustained virologic response (SVR). The effect of baseline and change (Δ) scores for composite and item-level self-efficacy on the cascade outcomes was assessed using logistic regression and generalized linear models. RESULTS: Higher baseline composite self-efficacy [adjusted odds ratio (95 % confidence interval) =1.57 (1.07, 2.29)], 'goal attainment' [1.31 (1.03, 1.67)] and 'having a positive effect' [1.33 (1.03, 1.74)] were associated with greater likelihood of treatment initiation. 'Δ Goal attainment' was significantly associated with SVR [1.63 (1.04, 2.53)]. 'Δ Being in control' and 'Δ working to improve' were associated with treatment adherence and duration, respectively. CONCLUSIONS: General health self-efficacy positively influences DAA treatment initiation among PWID. 'Goal attainment' facilitates the achievement of DAA treatment-related outcomes. Further studies should assess the effect of self-efficacy related to performing healthcare tasks specific to DAAs on the treatment-related outcomes.
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Antivirais , Hepatite C , Adesão à Medicação , Autoeficácia , Abuso de Substâncias por Via Intravenosa , Humanos , Masculino , Feminino , Adulto , Antivirais/uso terapêutico , Abuso de Substâncias por Via Intravenosa/psicologia , Abuso de Substâncias por Via Intravenosa/tratamento farmacológico , Abuso de Substâncias por Via Intravenosa/complicações , Pessoa de Meia-Idade , Adesão à Medicação/psicologia , Hepatite C/tratamento farmacológico , Hepatite C/psicologia , Resultado do Tratamento , Resposta Viral SustentadaRESUMO
Making a measurement over millions of nanoparticles or exposed crystal facets seldom reports on reactivity of a single nanoparticle or facet, which may depart drastically from ensemble measurements. Within the past 30 years, science has moved toward studying the reactivity of single atoms, molecules, and nanoparticles, one at a time. This shift has been fueled by the realization that everything changes at the nanoscale, especially important industrially relevant properties like those important to electrocatalysis. Studying single nanoscale entities, however, is not trivial and has required the development of new measurement tools. This review explores a tale of the clever use of old and new measurement tools to study electrocatalysis at the single entity level. We explore in detail the complex interrelationship between measurement method, electrocatalytic material, and reaction of interest (e.g., carbon dioxide reduction, oxygen reduction, hydrazine oxidation, etc.). We end with our perspective on the future of single entity electrocatalysis with a key focus on what types of measurements present the greatest opportunity for fundamental discovery.
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Fentanyl is an extremely potent opioid that is commonly laced into other drugs. Fentanyl poses a danger to users but also to responders or bystanders who may unknowingly ingest a lethal dose (â¼2 mg) of fentanyl from aerosolized powder or vapor. Electrochemistry offers a small, simple, and affordable platform for the direct detection of illicit substances; however, it is largely limited to solution-phase measurements. Here, we demonstrate the hands-free capture and electroanalyzation of aerosols containing fentanyl. A novel electrochemical cell is constructed by a microwire (cylindrical working electrode) traversing an ionic liquid film that is suspended within a conductive loop (reference/counter electrode). We provide a quantitative finite element simulation of the resulting electrochemical system. The suspended film maintains a high-surface area:volume, allowing the electrochemical cell to act as an effective aerosol collector. The low vapor pressure (negligible evaporation) of ionic liquid makes it a robust candidate for in-field applications, and the use of a hydrophobic ionic liquid allows for the extraction of fentanyl from solids and sprayed aqueous aerosols.
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Aerossóis , Técnicas Eletroquímicas , Fentanila , Fentanila/análise , Aerossóis/química , Aerossóis/análise , Líquidos Iônicos/química , Eletrodos , Analgésicos Opioides/análiseRESUMO
Building upon evidence supporting the co-occurrence of behavioural addictions, this study delved into the relationship between social media doomscrolling and celebrity worship among university student social media users in Iran and the United States. Objectives were threefold: (a) provide psychometric support for the Social Media Doomscrolling Scale (SMDS), (b) examine psychological correlates of doomscrolling and celebrity worship, and (c) explore the relationship between doomscrolling and celebrity worship. The SMDS demonstrated good psychometric properties in the US sample, like the original study of the SMDS conducted in an Iranian sample. Doomscrolling showed a positive association with future anxiety and a negative association with psychological well-being in both US and Iranian samples. Celebrity worship was positively linked with future anxiety in the Iranian and US samples. A positive correlation emerged between doomscrolling and celebrity worship in both the US and Iranian samples. This cross-cultural study offers preliminary evidence for the co-occurrence of two emerging media-related behavioural addictions.
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Telomeres are repetitive nucleoprotein complexes at chromosomal termini essential for maintaining genome stability. Telomeric RNA, or TERRA, is a previously presumed long noncoding RNA of heterogeneous lengths that contributes to end-capping structure and function, and facilitates telomeric recombination in tumors that maintain telomere length via the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway. Here, we investigated TERRA in the radiation-induced DNA damage response (DDR) across astronauts, high-altitude climbers, healthy donors, and cellular models. Similar to astronauts in the space radiation environment and climbers of Mt. Everest, in vitro radiation exposure prompted increased transcription of TERRA, while simulated microgravity did not. Data suggest a specific TERRA DDR to telomeric double-strand breaks (DSBs), and provide direct demonstration of hybridized TERRA at telomere-specific DSB sites, indicative of protective TERRA:telomeric DNA hybrid formation. Targeted telomeric DSBs also resulted in accumulation of TERRA foci in G2-phase, supportive of TERRA's role in facilitating recombination-mediated telomere elongation. Results have important implications for scenarios involving persistent telomeric DNA damage, such as those associated with chronic oxidative stress (e.g., aging, systemic inflammation, environmental and occupational radiation exposures), which can trigger transient ALT in normal human cells, as well as for targeting TERRA as a therapeutic strategy against ALT-positive tumors.
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Altitude , Voo Espacial , Telômero , Humanos , Telômero/metabolismo , Telômero/genética , Masculino , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Adulto , Pessoa de Meia-Idade , Quebras de DNA de Cadeia Dupla , Feminino , Dano ao DNA , Montanhismo , Homeostase do TelômeroRESUMO
Carbonate minerals are ubiquitous in nature, and their dissolution impacts many environmentally relevant processes including preferential flow during geological carbon sequestration, pH buffering with climate-change induced ocean acidification, and organic carbon bioavailability in melting permafrost. In this study, we advance the atomic level understanding of calcite dissolution mechanisms to improve our ability to predict this complex process. We performed high pressure and temperature (1300 psi and 50 °C) batch experiments to measure transient dissolution of freshly cleaved calcite under H2O, H+, and H2CO3-dominated conditions, without and with an inhibitory anionic surfactant present. Before and after dissolution experiments, we measured dissolution etch-pit geometries using laser profilometry, and we used density functional theory to investigate relative adsorption energies of competing species that affect dissolution. Our results support the hypothesis that calcite dissolution is controlled by the ability of H2O to preferentially adsorb to surface Ca atoms over competing species, even when dissolution is dominated by H+ or H2CO3. More importantly, we identify for the first time that adsorbed H+ enhances the role of water by weakening surface Ca-O bonds. We also identify that H2CO3 undergoes dissociative adsorption resulting in adsorbed HCO3- and H+. Adsorbed HCO3- that competes with H2O for Ca acute edge sites inhibits dissolution, while adsorbed H+ at the neighboring surface of CO3 enhances dissolution. The net effect of the dissociative adsorption of H2CO3 is enhanced dissolution. These results will impact future efforts to more accurately model the impact of solutes in complex water matrices on carbonate mineral dissolution.
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Carbonato de Cálcio , Ácido Carbônico , Prótons , Água , Carbonato de Cálcio/química , Ácido Carbônico/química , Água/química , Solubilidade , AdsorçãoRESUMO
Most COVID-19 vaccines contain the SARS-CoV-2 spike protein as an antigen, but they lose efficacy as neutralizing antibody titers wane and escape variants emerge. Modifying the spike antigen to increase neutralizing antibody titers would help counteract this decrease in titer. We previously used a structure-based computational design method to identify nine amino acid changes in the receptor-binding domain (RBD) of spike that stabilize the RBD and increase the neutralizing antibody titers elicited by vaccination. Here, we introduce those enhancing amino acid changes into a full-length spike (FL-S-2P) ectodomain representative of most approved vaccine antigens. These amino acid changes can be incorporated into the FL-S-2P protein without negatively effecting expression or stability. Furthermore, the amino acid changes improved functional antibody titers in both mice and monkeys following vaccination. These amino acid changes could increase the duration of protection conferred by most COVID-19 vaccines.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Vacinas contra COVID-19/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , Camundongos , COVID-19/imunologia , COVID-19/prevenção & controle , Humanos , Vacinação , Feminino , Domínios Proteicos/imunologiaRESUMO
Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space1-6. Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study7, JAXA CFE study8,9, SpaceX Inspiration4 crew10-12, Axiom and Polaris. The SOMA resource represents a more than tenfold increase in publicly available human space omics data, with matched samples available from the Cornell Aerospace Medicine Biobank. The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome datasets, which reveal some consistent features across missions, including cytokine shifts, telomere elongation and gene expression changes, as well as mission-specific molecular responses and links to orthologous, tissue-specific mouse datasets. Leveraging the datasets, tools and resources in SOMA can help to accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation and countermeasure data for upcoming lunar, Mars and exploration-class missions.
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Malaria is caused by eukaryotic protozoan parasites of the genus Plasmodium. There are 249 million new cases and 608,000 deaths annually, and new interventions are desperately needed. Malaria vaccines can be divided into three categories: liver stage, blood stage, or transmission-blocking vaccines. Transmission-blocking vaccines prevent the transmission of disease by the mosquito vector from one human to another. Pfs230 is one of the leading transmission-blocking vaccine antigens for malaria. Here, we describe the development of a 24-copy self-assembling nanoparticle vaccine comprising domain 1 of Pfs230 genetically fused to H. pylori ferritin. The single-component Pfs230D1-ferritin construct forms a stable and homogenous 24-copy nanoparticle with good production yields. The nanoparticle is highly immunogenic, as two low-dose vaccinations of New Zealand White rabbits elicited a potent and durable antibody response with high transmission-reducing activity when formulated in two distinct adjuvants suitable for translation to human use. This single-component 24-copy Pfs230D1-ferritin nanoparticle vaccine has the potential to improve production pipelines and the cost of manufacturing a potent and durable transmission-blocking vaccine for malaria control.
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Quorum sensing (QS) is a cell-cell signaling system that enables bacteria to coordinate population density-dependent changes in behavior. This chemical communication pathway is mediated by diffusible N-acyl L-homoserine lactone signals and cytoplasmic signal-responsive LuxR-type receptors in Gram-negative bacteria. As many common pathogenic bacteria use QS to regulate virulence, there is significant interest in disrupting QS as a potential therapeutic strategy. Prior studies have implicated the natural products salicylic acid, cinnamaldehyde and other related benzaldehyde derivatives as inhibitors of QS in the opportunistic pathogen Pseudomonas aeruginosa, yet we lack an understanding of the mechanisms by which these compounds function. Herein, we evaluate the activity of a set of benzaldehyde derivatives using heterologous reporters of the P. aeruginosa LasR and RhlR QS signal receptors. We find that most tested benzaldehyde derivatives can antagonize LasR or RhlR reporter activation at micromolar concentrations, although certain molecules also caused mild growth defects and nonspecific reporter antagonism. Notably, several compounds showed promising RhlR or LasR specific inhibitory activities over a range of concentrations below that causing toxicity. Ortho-Vanillin, a previously untested compound, was the most promising within this set. Competition experiments against the native ligands for LasR and RhlR revealed that ortho-vanillin can interact competitively with RhlR but not with LasR. Overall, these studies expand our understanding of benzaldehyde activities in the LasR and RhlR receptors and reveal potentially promising effects of ortho-vanillin as a small molecule QS modulator against RhlR.
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BACKGROUND: A large body of evidence suggests that some people have a strong, obsessive attachment to a favorite celebrity. The absorption-addiction model attempts to account for this extreme attachment, sometimes labeled "celebrity worship." According to the model, a small portion of celebrity admirers ("celebrity worshipers") become absorbed in the personal lives of celebrities to compensate for perceived personal or social deficiencies. The purpose of this study is to examine how the absorption-addiction model relates to broader psychological theories that include non-celebrity contexts. Specifically, we examine how the absorption-addiction model relates to three theories: empty-self theory, extremism theory, and the dualistic model of passion. METHODS: Participants (N = 399; 77.94% women, Mage = 19.91 years, SD = 3.24) completed an online questionnaire measuring attraction to favorite celebrities. Constructs representing the three broader theories were compared to a measure of attraction to one's favorite celebrity. RESULTS: Sense of emptiness, obsessive passion, and extremism were positively associated with celebrity attraction. The strongest association was found with extremism, though the effect was moderate. CONCLUSIONS: These findings suggest that extremism theory is the best fit of the three broader theories explaining celebrity worship, although its contribution to understanding celebrity worship is modest.
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Pessoas Famosas , Humanos , Feminino , Masculino , Adulto , Adulto Jovem , Modelos Psicológicos , Apego ao Objeto , Teoria Psicológica , Comportamento Aditivo/psicologia , AdolescenteRESUMO
Background and aims: Celebrity worship, defined as an excessive admiration towards celebrities, has generated considerable research and public interest. A widely used assessment instrument to measure celebrity worship is the 23-item Celebrity Attitude Scale. However, concerns have been raised regarding the measurement, including the inconsistent factor structure and lack of a cut-off point to identify "celebrity worshipers". The present study aims to address these concerns by testing the psychometric appropriateness of a short, 7-item version of the CAS (i.e., CAS-7) and estimating the prevalence of individuals with high-level celebrity admiration using a representative sample of Hungarian adults (between 18 and 64 years of age) according to gender, age, geographic location, and size of residence. Methods: The total sample comprised 2028 respondents, of which 769 valid responses were administered from participants who reported having a favorite celebrity (51.11% men, Mage = 36.38 years, SD = 13.36). Results: Results indicated an excellent model fit for the two-factor and bifactor model of the CAS-7. Based on the suggested cut-off score of 26, the prevalence of high-level celebrity admiration is 4.53% in the Hungarian adult population (18-64 years of age) and 8.51% among young adults (18-34 years of age). Individuals with this high level of admiration towards a favorite celebrity reported more symptoms of problematic Internet use, depression, anxiety, and stress than individuals with general celebrity admiration levels. Discussion and conclusions: The CAS-7 demonstrated sound psychometric properties, confirming its applicability in research and practice.
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Atitude , Psicometria , Humanos , Masculino , Adulto , Feminino , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Hungria/epidemiologia , Psicometria/instrumentação , Psicometria/normas , Prevalência , Pessoas Famosas , Inquéritos e QuestionáriosRESUMO
Background: The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure. Methods: To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction. Telomere length was measured by quantitative PCR, while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations. A robust bioinformatic pipeline was used for data analysis, including variant calling to assess mutational burden. Result: Telomere elongation occurred during spaceflight and shortened after return to Earth. Cell-free DNA analysis revealed increased immune cell signatures post-flight. No significant clonal hematopoiesis of indeterminate potential (CHIP) or whole-genome instability was observed. The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight. Conclusion: Our findings provide valuable insights into the physiological consequences of short-duration spaceflight, with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth. CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts, an understudied phenomenon as previous studies have focused on career astronauts. This study will serve as a reference point for future commercial and non-commercial spaceflight, low Earth orbit (LEO) missions, and deep-space exploration.
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DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Minimally invasive surgery (MIS) with integrated enhanced recovery pathways (ERPs) helps reduce length of stay and improve surgical outcomes. As these procedures have become more prevalent over time, pharmacists are in key positions to manage medications in the perioperative space to help optimize transitions of care and reduce safety events. Here we identify several clinical areas across phases of care for these procedures in which the knowledge and guidance of pharmacists, as members of the interprofessional team, are paramount. SUMMARY: Perioperative pharmacy expertise is often required for MIS procedures in the areas of acid suppression, antithrombotic management, blood glucose control, drug formulation, immunosuppressant optimization, pain mitigation, and postoperative nausea and vomiting prevention and treatment. For each MIS procedure, pharmacists should identify and consider diet and anatomical changes as well as patient- and surgery-specific risk factors. Pharmacists can then utilize their knowledge of the pharmacokinetics and pharmacodynamics of individual medications along with evidence-based medicine to recommend selection of appropriate agents. CONCLUSION: Pharmacist contributions to perioperative medication management for MIS procedures can improve care as surgical patients navigate transitions through the perioperative setting. Pharmacists can further incorporate medication expertise through development and implementation of institutional MIS protocols within the context of ERPs. As such, any pharmacist should feel empowered to aid in the care of surgical patients.
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BACKGROUND: It is well documented that public safety personnel are exposed to potentially traumatic events (PTEs) at elevated frequency and demonstrate higher prevalence of trauma-related symptoms compared to the general population. Lesser studied to date are the organizational consequences of workplace PTE exposure and associated mental health outcomes such as acute/posttraumatic stress disorder (ASD/PTSD), depression, and anxiety. METHODS: The present review synthesizes international literature on work outcomes in public safety personnel (PSP) to explore whether and how PTE and trauma-related symptoms relate to workplace outcomes. A total of N = 55 eligible articles examining PTE or trauma-related symptoms in relation to work outcomes were systematically reviewed using best-evidence narrative synthesis. RESULTS: Three primary work outcomes emerged across the literature: absenteeism, productivity/performance, and costs to organization. Across n = 21 studies of absenteeism, there was strong evidence that PTE or trauma-related symptoms are associated with increased sickness absence. N = 27 studies on productivity/performance demonstrated overall strong evidence of negative impacts in the workplace. N = 7 studies on cost to organizations demonstrated weak evidence that PTE exposure or trauma-related mental health outcomes are associated with increased cost to organization. CONCLUSIONS: Based on available evidence, the experience of workplace PTE or trauma-related symptoms is associated with negative impact on PSP occupational functioning, though important potential confounds (e.g., organizational strain and individual risk factors) remain to be more extensively investigated.