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1.
Artigo em Inglês | MEDLINE | ID: mdl-38811488

RESUMO

Visual search can be guided by biasing one's attention towards features associated with a target. Prior work has shown that high-fidelity, picture-based cues are more beneficial to search than text-based cues. However, typically picture cues provide both detailed form information and color information that is absent from text-based cues. Given that visual resolution deteriorates with eccentricity, it is not clear that high-fidelity form information would benefit guidance to peripheral objects - much of the picture benefit could be due to color information alone. To address this, we conducted a search task with eye-tracking that had four types of cues that comprised a 2 (text/pictorial cue) × 2 (no color/color) design. We hypothesized that color information would be important for efficient search guidance while high-fidelity form information would be important for efficient verification times. In Experiment 1 cues were a colored picture of the target, a gray-scaled picture of the target, a text-based cue that included color (e.g., "blue shoe"), or a text-based cue without color (e.g., "shoe"). Experiment 2 was a replication of Experiment 1, except that the color word in the text-based cue was presented in the precise color that was the dominant color in the target. Our results show that high-fidelity form information is important for efficient verifications times (with color playing less of a role) and color is important for efficient guidance, but form information also benefits guidance. These results suggest that different features of the cue independently contribute to different aspects of the search process.

2.
Res Sq ; 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37720034

RESUMO

SARS-CoV-2 initiates infection in the conducting airways, which rely on mucocilliary clearance (MCC) to minimize pathogen penetration. However, it is unclear how MCC impacts SARS-CoV-2 spread after infection is established. To understand viral spread at this site, we performed live imaging of SARS-CoV-2 infected differentiated primary human bronchial epithelium cultures for up to 9 days. Fluorescent markers for cilia and mucus allowed longitudinal monitoring of MCC, ciliary motion, and infection. The number of infected cells peaked at 4 days post-infection in characteristic foci that followed mucus movement. Inhibition of MCC using physical and genetic perturbations limited foci. Later in infection, MCC was diminished despite relatively subtle ciliary function defects. Resumption of MCC and infection spread after mucus removal suggests that mucus secretion mediates this effect. We show that MCC facilitates SARS-CoV-2 spread early in infection while later decreases in MCC inhibit spread, suggesting a complex interplay between SARS-CoV-2 and MCC.

3.
Transfusion ; 63(10): 1904-1915, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37622403

RESUMO

BACKGROUND: In the United States, source plasma (SP) donors can donate up to 104 times per year. Considering the global need for SP and plasma-derived medicinal products, it is critical to maintain the health of frequent donors. This study explores SP donors' self-reported reasons for a lapse in donating. STUDY DESIGN AND METHODS: There were 5608 SP donors from 14 SP centers who enrolled in a longitudinal cohort study to assess self-reported functional health and well-being. Donors were assigned to one of four groups, according to the frequency of SP donation in the 12 months before enrollment. One thousand four hundred forty-eight SP donors who lapsed in donating during 6 months or greater during the study follow-up were asked to complete a survey. RESULTS: There were 545 lapsed SP donors who returned surveys (37.6%); 63% were female. Most responses given for stopping SP donation were categorized as convenience reasons (69.1%). Self-reported health concerns, including being deferred multiple times, which were categorized as possibly related or unable to determine a relationship to plasmapheresis, represented 45.5% of the responses. DISCUSSION: Primary reasons US SP donors report for a lapse in donation were categorized as convenience (e.g., schedule conflicts/lack of time). Donor responses categorized as health concerns which have a possible or uncertain relationship to plasmapheresis were less frequent but present in all frequency groups. This study adds to the body of evidence that SP donors cease donating for a variety of self-reported reasons with the majority not directly related to a perceived negative impact on their health.


Assuntos
Doadores de Sangue , Humanos , Feminino , Masculino , Estudos Longitudinais , Inquéritos e Questionários , Estudos de Coortes , Autorrelato
4.
Transfusion ; 63(10): 1885-1903, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37622454

RESUMO

BACKGROUND: Plasma-derived medicinal products (PDMPs) are essential, life-saving medicines manufactured from plasma donated by healthy human volunteers. PDMPs are used to treat a range of rare, serious, and chronic conditions, often genetic in origin. Approximately 70% of the Source Plasma (SP) used for PDMP manufacturing comes from United States (US). The hypothesis of the study is that US donation frequency does not impair donor self-reported functional health and well-being. STUDY DESIGN AND METHODS: A total of 5608 SP donors from 14 US SP centers were enrolled in a cross-sectional study to assess self-reported health related quality of life (HRQoL) and well-being. By sex, donors were assigned to one of four groups, according to their frequency of SP donation in the 12 months before enrollment. The SF-36v2® Health Survey (SF-36v2) and a survey assessing the frequency of various health conditions that may be associated with impaired immune function over different time periods were used. RESULTS: There were no statistically significant differences in SF-36v2 scores between any of the donor frequency groups, compared with new donors after controlling for potential confounding and accounting for multiple comparisons among males and females. Cough, cold, occasional fatigue, and sore throat were the most reported health conditions or symptoms, but there was no clear difference among sex or frequency groups. DISCUSSION: The self-reported data in this study support the hypothesis that compensated donations at US FDA permitted frequencies and volumes are consistent with maintaining donor health. Compared with the general population, SP donors have comparable or better health than the general population.


Assuntos
Doadores de Sangue , Qualidade de Vida , Masculino , Feminino , Humanos , Estados Unidos , Estudos Transversais , Inquéritos e Questionários , Autorrelato
5.
Microbiol Spectr ; : e0491722, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36916917

RESUMO

Vibrio cholerae is a Gram-negative pathogen, living in constant competition with other bacteria in marine environments and during human infection. One competitive advantage of V. cholerae is the ability to metabolize diverse carbon sources, such as chitin and citrate. We observed that when some V. cholerae strains were grown on a medium with citrate, the medium's chemical composition turned into a hostile alkaline environment for Gram-negative bacteria, such as Escherichia coli and Shigella flexneri. We found that although the ability to exclude competing bacteria was not contingent on exogenous citrate, V. cholerae C6706 citrate metabolism mutants ΔoadA-1, ΔcitE, and ΔcitF were not able to inhibit S. flexneri or E. coli growth. Lastly, we demonstrated that while the V. cholerae C6706-mediated increased medium pH was necessary for the enteric exclusion phenotype, secondary metabolites, such as bicarbonate (protonated to carbonate in the raised pH) from the metabolism of citrate, enhanced the ability to inhibit the growth of E. coli. These data provide a novel example of how V. cholerae outcompetes other Gram-negative bacteria. IMPORTANCE Vibrio cholerae must compete with other bacteria in order to cause disease. Here, we show that V. cholerae creates an alkaline environment, which is able to inhibit the growth of other enteric bacteria. We demonstrate that V. cholerae environmental alkalization is linked to the capacity of the bacteria to metabolize citrate. This behavior could potentially contribute to V. cholerae's ability to colonize the human intestine.

6.
Health Sci Rep ; 6(1): e1062, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36712813

RESUMO

Background and Aims: Labels designed to communicate critical information are paramount for the safe and effective use of over-the-counter medications; in recognition of this, the content and formatting of over the counter (OTC) labels sold in interstate commerce has been regulated for decades. Yet, available studies suggest that consumers frequently rely on limited information during decision making, failing to access the information required in the Drug Facts Label. This is particularly important for older consumers, who are at greater risk for adverse reactions to medicines. In two experiments we objectively evaluate how novel label designs that employ highlighting and a warning label placed on the package's front impact older consumers' attention to, and use of, critical information. Methods: In Experiment 1, 68 OTC patients (65+) engaged with a computer-based task answering yes/no scenario-based questions about a drug's appropriateness. In Experiment 2, 63 OTC patients (65+) conducted a forced-choice task where one of two drugs presented on a computer screen was appropriate for a provided scenario while the other was not. Both tasks required participants to access and use critical label information (i.e., warnings or active ingredients) to respond correctly. Dependent variables analyzed were the proportion of correct responses and time to correct response. Results: Highlighting or placing critical information on the front of the package significantly improved response accuracy and time to correct response in Experiment 1 as compared to responses utilizing the standard label. For Experiment 2, participants were faster and more accurate when critical information was highlighted. Conclusions: Results provide direct measures of the efficacy of novel labeling strategies. This information is relevant for regulations which dictate label design in ways that enhance ease and safety of use of medications for older adults.

7.
Psychol Res ; 87(3): 800-815, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35790565

RESUMO

The self-generation effect refers to the finding that people's memory for information tends to be better when they generate it themselves. Counterintuitively, when proofreading, this effect may make it more difficult to detect mistakes in one's own writing than in others' writing. We investigated the self-generation effect and sources of individual differences in proofreading performance in two eye-tracking experiments. Experiment 1 failed to reveal a self-generation effect. Experiment 2 used a studying manipulation to induce overfamiliarity for self-generated text, revealing a weak but non-significant self-generation effect. Overall, word errors (i.e., wrong words) were detected less often than non-word errors (i.e., misspellings), and function word errors were detected less often than content word errors. Fluid intelligence predicted proofreading performance, whereas reading comprehension, working memory capacity, processing speed, and indicators of miserly cognitive processing did not. Students who made more text fixations and spent more time proofreading detected more errors.


Assuntos
Processos Mentais , Leitura , Humanos , Efeito de Coortes , Redação , Compreensão
8.
Atten Percept Psychophys ; 84(8): 2461-2471, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36258142

RESUMO

Models of visual search posit that target absent responses occur when the quitting threshold for the trial is reached before a target is detected, and that feedback about missed targets allows the quitting threshold to be adaptively set to the difficulty of the search task. While these models may effectively capture processes in lab-based tasks, in real-world searches feedback is often impossible to provide. Instead, observers have little information about their errors, and may only be aware of when they successfully detect the target. We posit that in the absence of feedback the time required to find a target might influence quitting thresholds. In three experiments, we investigate how manipulating the mean time and the standard deviation of time to detect a target influence quitting thresholds in target absent trials. To vary target detection times while holding the search stimuli constant, we used an eye-movement contingent change to surreptitiously introduce a target near fixation at a particular time. Results show that decreasing the mean time to find a target also decreases the number of items inspected and reaction time in target absent trials, the hallmark of a shift in the quitting threshold. By contrast, varying the standard deviation around a fixed mean had no impact on target absent search times. These findings suggest that people are sensitive to the typical time required to find a target in a given task and use that information to flexibly adjust target absent quitting thresholds, but people are not sensitive to the variability.


Assuntos
Atenção , Movimentos Oculares , Humanos , Atenção/fisiologia , Tempo de Reação/fisiologia , Conscientização , Percepção Visual/fisiologia
9.
EMBO J ; 41(17): e110784, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35859387

RESUMO

The mitochondrial intermembrane space protein AIFM1 has been reported to mediate the import of MIA40/CHCHD4, which forms the import receptor in the mitochondrial disulfide relay. Here, we demonstrate that AIFM1 and MIA40/CHCHD4 cooperate beyond this MIA40/CHCHD4 import. We show that AIFM1 and MIA40/CHCHD4 form a stable long-lived complex in vitro, in different cell lines, and in tissues. In HEK293 cells lacking AIFM1, levels of MIA40 are unchanged, but the protein is present in the monomeric form. Monomeric MIA40 neither efficiently interacts with nor mediates the import of specific substrates. The import defect is especially severe for NDUFS5, a subunit of complex I of the respiratory chain. As a consequence, NDUFS5 accumulates in the cytosol and undergoes rapid proteasomal degradation. Lack of mitochondrial NDUFS5 in turn results in stalling of complex I assembly. Collectively, we demonstrate that AIFM1 serves two overlapping functions: importing MIA40/CHCHD4 and constituting an integral part of the disulfide relay that ensures efficient interaction of MIA40/CHCHD4 with specific substrates.


Assuntos
Fator de Indução de Apoptose , Complexo I de Transporte de Elétrons , Proteínas de Transporte da Membrana Mitocondrial , Fator de Indução de Apoptose/metabolismo , Dissulfetos/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Células HEK293 , Humanos , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Oxirredução , Transporte Proteico
10.
Res Sq ; 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35411346

RESUMO

The systemic nature of SARS-CoV-2 infection is highly recognized, but poorly characterized. A non-invasive and unbiased method is needed to clarify whole body spatiotemporal dynamics of SARS-CoV-2 infection after transmission. We recently developed a probe based on the anti-SARS-CoV-2 spike antibody CR3022 to study SARS-CoV-2 pathogenesis in vivo. Herein, we describe its use in immunoPET to investigate SARS-CoV-2 infection of three rhesus macaques. Using PET/CT imaging of macaques at different times post-SARS-CoV-2 inoculation, we track the 64Cu-labelled CR3022-F(ab')2 probe targeting the spike protein of SARS-CoV-2 to study the dynamics of infection within the respiratory tract and uncover novel sites of infection. Using this method, we uncovered differences in lung pathology between infection with the WA1 isolate and the delta variant, which were readily corroborated through computed tomography scans. The 64Cu-CR3022-probe also demonstrated dynamic changes occurring between 1- and 2-weeks post-infection. Remarkably, a robust signal was seen in the male genital tract (MGT) of all three animals studied. Infection of the MGT was validated by immunofluorescence imaging of infected cells in the testicular and penile tissue and severe pathology was observed in the testes of one animal at 2-weeks post-infection. The results presented here underscore the utility of using immunoPET to study the dynamics of SARS-CoV-2 infection to understand its pathogenicity and discover new anatomical sites of viral replication. We provide direct evidence for SARS-CoV-2 infection of the MGT in rhesus macaques revealing the possible pathologic outcomes of viral replication at these sites.

11.
bioRxiv ; 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35262081

RESUMO

The systemic nature of SARS-CoV-2 infection is highly recognized, but poorly characterized. A non-invasive and unbiased method is needed to clarify whole body spatiotemporal dynamics of SARS-CoV-2 infection after transmission. We recently developed a probe based on the anti-SARS-CoV-2 spike antibody CR3022 to study SARS-CoV-2 pathogenesis in vivo. Herein, we describe its use in immunoPET to investigate SARS-CoV-2 infection of three rhesus macaques. Using PET/CT imaging of macaques at different times post-SARS-CoV-2 inoculation, we track the 64Cu-labelled CR3022-F(ab')2 probe targeting the spike protein of SARS-CoV-2 to study the dynamics of infection within the respiratory tract and uncover novel sites of infection. Using this method, we uncovered differences in lung pathology between infection with the WA1 isolate and the delta variant, which were readily corroborated through computed tomography scans. The 64Cu-CR3022-probe also demonstrated dynamic changes occurring between 1- and 2-weeks post-infection. Remarkably, a robust signal was seen in the male genital tract (MGT) of all three animals studied. Infection of the MGT was validated by immunofluorescence imaging of infected cells in the testicular and penile tissue and severe pathology was observed in the testes of one animal at 2-weeks post-infection. The results presented here underscore the utility of using immunoPET to study the dynamics of SARS-CoV-2 infection to understand its pathogenicity and discover new anatomical sites of viral replication. We provide direct evidence for SARS-CoV-2 infection of the MGT in rhesus macaques revealing the possible pathologic outcomes of viral replication at these sites.

12.
J Am Pharm Assoc (2003) ; 62(1): 167-175.e1, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34503908

RESUMO

BACKGROUND: Over-the-counter (OTC) medication use is associated with risks of adverse drug reactions (ADRs), particularly among older adults. The Drug Facts Label (DFL) is supposed to provide consumers with information that would avoid ADRs, yet research suggests that consumers frequently fail to interact with this critical information. We postulate that emphasizing critical information by placing it on the front of the package may increase its usage. Before doing so, the most critical information from the DFL needs to be identified. OBJECTIVES: This study aimed to determine which information from the DFL is most critical in reducing ADRs at the time of purchase or use by older adults. METHODS: A national survey of practicing pharmacists knowledgeable about OTC medication use by older adults asked participants to rank order the importance of the DFL sections to reduce ADRs in older adults. Open-ended questions focused on identifying ways of improving OTC medication labeling. Quantitative rankings were used to calculate the content validity ratio and analyzed using Wilcoxon signed rank tests. Qualitative results were categorized into themes. RESULTS: A total of 318 responses (12% response rate) were analyzed. There was high consensus that uses and purpose, active ingredient, warnings, and directions for use were the most important sections of the DFL. Within the warning section, 2 specific warnings, "Do not use" and "Ask a doctor or pharmacist," were deemed most important. Similarly, qualitative themes focused on seeking health care provider assistance or were specific to age-related precautions. CONCLUSIONS: Prioritizing warnings that highlight the importance of possible drug-drug and drug-disease precautions and the need to seek medical advice before taking OTC medications were deemed most critical. Moving this type of information to the front of the package may help reduce ADRs among older adults.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Farmacêuticos , Idoso , Comportamento do Consumidor , Aconselhamento , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Medicamentos sem Prescrição/efeitos adversos
13.
PLoS One ; 16(12): e0260857, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34882728

RESUMO

HPV infection results in changes in host gene methylation which, in turn, are thought to contribute to the neoplastic progression of HPV-associated cancers. The objective of this study was to identify joint and disease-specific genome-wide methylation changes in anal and cervical cancer as well as changes in high-grade pre-neoplastic lesions. Formalin-fixed paraffin-embedded (FFPE) anal tissues (n = 143; 99% HPV+) and fresh frozen cervical tissues (n = 28; 100% HPV+) underwent microdissection, DNA extraction, HPV genotyping, bisulfite modification, DNA restoration (FFPE) and analysis by the Illumina HumanMethylation450 Array. Differentially methylated regions (DMR; t test q<0.01, 3 consecutive significant CpG probes and mean Δß methylation value>0.3) were compared between normal and cancer specimens in partial least squares (PLS) models and then used to classify anal or cervical intraepithelial neoplasia-3 (AIN3/CIN3). In AC, an 84-gene PLS signature (355 significant probes) differentiated normal anal mucosa (NM; n = 9) from AC (n = 121) while a 36-gene PLS signature (173 significant probes) differentiated normal cervical epithelium (n = 10) from CC (n = 9). The CC progression signature was validated using three independent publicly available datasets (n = 424 cases). The AC and CC progression PLS signatures were interchangeable in segregating normal, AIN3/CIN3 and AC and CC and were found to include 17 common overlapping hypermethylated genes. Moreover, these signatures segregated AIN3/CIN3 lesions similarly into cancer-like and normal-like categories. Distinct methylation changes occur across the genome during the progression of AC and CC with overall similar profiles and add to the evidence suggesting that HPV-driven oncogenesis may result in similar non-random methylomic events. Our findings may lead to identification of potential epigenetic drivers of HPV-associated cancers and also, of potential markers to identify higher risk pre-cancerous lesions.


Assuntos
Neoplasias do Ânus/patologia , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Genoma Humano , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Neoplasias do Ânus/genética , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Ensaios Clínicos Fase III como Assunto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/terapia , Adulto Jovem
14.
Matrix Biol Plus ; 12: 100078, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34355160

RESUMO

Elastic tissues owe their functional properties to the composition of their extracellular matrices, particularly the range of extracellular, multidomain extensible elastic fibre and microfibrillar proteins. These proteins include elastin, fibrillin, latent TGFß binding proteins (LTBPs) and collagens, where their biophysical and biochemical properties not only give the matrix structural integrity, but also play a vital role in the mechanisms that underlie tissue homeostasis. Thus far structural information regarding the structure and hierarchical assembly of these molecules has been challenging and the resolution has been limited due to post-translational modification and their multidomain nature leading to flexibility, which together result in conformational and structural heterogeneity. In this review, we describe some of the matrix proteins found in elastic fibres and the new emerging techniques that can shed light on their structure and dynamic properties.

15.
Transfusion ; 61(10): 2941-2957, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34390267

RESUMO

BACKGROUND: Source plasma (SP) is the primary starting material for 87% of plasma-derived medicinal products globally. Plasmavigilance is a program designed to collect, analyze, and monitor donor adverse events (AEs) across the SP collection industry. Donor retention depends on donors having a safe and satisfactory experience. This study analyzes AE rates and SP donor characteristics that may be predictors of an AE. STUDY DESIGN AND METHODS: Donation data for 1.1 million donors making 12,183,182 SP donations over a 4-month period were analyzed. This represented approximately 72% of the donations collected by the U.S. plasma industry. The Standard for Recording Donor Adverse Events was used for AE definitions and classifications. RESULTS: The overall AE rate was 15.85/104 donations. The two AEs with the highest rates were Hypotensive and Phlebotomy events (8.32 and 5.91/104 donations, respectively). Females had higher overall AE rates than males (25.76 vs. 9.85/104 donations), and first-time donors had higher overall AE rates than repeat donors (136.66 vs. 12.37/104 donations). Weight, body mass index, age, and pre-donation estimated blood volume also were predictors of AE. DISCUSSION: SP donors have low AE rates with 90% being events classified as Hypotensive or Phlebotomy. Special attention and mitigation strategies should be directed to donors who are young, lightweight (between 100 and 124 pounds), female, or first-time donors to further reduce the incidence of AE, continue to ensure the donor has a safe experience, and facilitate donor retention.


Assuntos
Doadores de Sangue , Coleta de Amostras Sanguíneas/efeitos adversos , Plasma , Adulto , Fatores Etários , Volume Sanguíneo , Feminino , Humanos , Hipotensão/etiologia , Masculino , Flebotomia/efeitos adversos , Plasma/química , Fatores de Risco , Fatores Sexuais , Estados Unidos
16.
Neurol Res Pract ; 3(1): 31, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34059132

RESUMO

BACKGROUND: The prehospital identification of stroke patients with large-vessel occlusion (LVO), that should be immediately transported to a thrombectomy capable centre is an unsolved problem. Our aim was to determine whether implementation of a state-wide standard operating procedure (SOP) using the Los Angeles Motor Scale (LAMS) is feasible and enables correct triage of stroke patients to hospitals offering (comprehensive stroke centres, CSCs) or not offering (primary stroke centres, PSCs) thrombectomy. METHODS: Prospective study involving all patients with suspected acute stroke treated in a 4-month period in a state-wide network of all stroke-treating hospitals (eight PSCs and two CSCs). Primary endpoint was accuracy of the triage SOP in correctly transferring patients to CSCs or PSCs. Additional endpoints included the number of secondary transfers, the accuracy of the LAMS for detection of LVO, apart from stroke management metrics. RESULTS: In 1123 patients, use of a triage SOP based on the LAMS allowed triage decisions according to LVO status with a sensitivity of 69.2% (95% confidence interval (95%-CI): 59.0-79.5%) and a specificity of 84.9% (95%-CI: 82.6-87.3%). This was more favourable than the conventional approach of transferring every patient to the nearest stroke-treating hospital, as determined by geocoding for each patient (sensitivity, 17.9% (95%-CI: 9.4-26.5%); specificity, 100% (95%-CI: 100-100%)). Secondary transfers were required for 14 of the 78 (17.9%) LVO patients. Regarding the score itself, LAMS detected LVO with a sensitivity of 67.5% (95%-CI: 57.1-78.0%) and a specificity of 83.5% (95%-CI: 81.0-86.0%). CONCLUSIONS: State-wide implementation of a triage SOP requesting use of the LAMS tool is feasible and improves triage decision-making in acute stroke regarding the most appropriate target hospital.

17.
Cogn Res Princ Implic ; 6(1): 40, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34041617

RESUMO

Over-the-counter (OTC) drugs have many benefits but also carry risks, such as adverse drug reactions, which are more prevalent in older adults. Because these products do not require the oversight of a physician or pharmacist, labeling plays a key role in communicating information required for their safe and effective use. Research suggests that current labels are not terribly effective at communicating potential risk. One reason for their lack of effectiveness is that few consumers attend to critical information (active ingredients and warnings) when making purchases. In two experiments, we used a change detection task to objectively evaluate how novel label designs that employ highlighting and a warning label placed on the package's front impact attention to critical information among older participants (65 and older). The change detection task is a unique form of visual search which allowed us to assess the attentional priority of critical information among participants who were not explicitly instructed to search for this critical information. This unique aspect of the task is important given research suggesting that consumers rarely have the explicit goal of seeking out warnings and active ingredients when making OTC selections. Our results provide empirical support that both highlighting critical information and positioning it on the package's front increase its attentional prioritization relative to current, commercial practice. Given that attending to the critical information is prerequisite to utilizing that information, strategies that elicit attention in this way are likely to reduce medication errors.


Assuntos
Comportamento do Consumidor , Medicamentos sem Prescrição , Idoso , Humanos , Motivação , Medicamentos sem Prescrição/efeitos adversos , Rotulagem de Produtos
18.
Mol Cell ; 81(12): 2656-2668.e8, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-33930332

RESUMO

A deficient interferon (IFN) response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated as a determinant of severe coronavirus disease 2019 (COVID-19). To identify the molecular effectors that govern IFN control of SARS-CoV-2 infection, we conducted a large-scale gain-of-function analysis that evaluated the impact of human IFN-stimulated genes (ISGs) on viral replication. A limited subset of ISGs were found to control viral infection, including endosomal factors inhibiting viral entry, RNA binding proteins suppressing viral RNA synthesis, and a highly enriched cluster of endoplasmic reticulum (ER)/Golgi-resident ISGs inhibiting viral assembly/egress. These included broad-acting antiviral ISGs and eight ISGs that specifically inhibited SARS-CoV-2 and SARS-CoV-1 replication. Among the broad-acting ISGs was BST2/tetherin, which impeded viral release and is antagonized by SARS-CoV-2 Orf7a protein. Overall, these data illuminate a set of ISGs that underlie innate immune control of SARS-CoV-2/SARS-CoV-1 infection, which will facilitate the understanding of host determinants that impact disease severity and offer potential therapeutic strategies for COVID-19.


Assuntos
Antígenos CD/genética , Interações Hospedeiro-Patógeno/genética , Fatores Reguladores de Interferon/genética , Interferon Tipo I/genética , SARS-CoV-2/genética , Proteínas Virais/genética , Animais , Antígenos CD/química , Antígenos CD/imunologia , Sítios de Ligação , Linhagem Celular Tumoral , Chlorocebus aethiops , Retículo Endoplasmático/genética , Retículo Endoplasmático/imunologia , Retículo Endoplasmático/virologia , Proteínas Ligadas por GPI/química , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/imunologia , Regulação da Expressão Gênica , Complexo de Golgi/genética , Complexo de Golgi/imunologia , Complexo de Golgi/virologia , Células HEK293 , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Fatores Reguladores de Interferon/classificação , Fatores Reguladores de Interferon/imunologia , Interferon Tipo I/imunologia , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , SARS-CoV-2/imunologia , Transdução de Sinais , Células Vero , Proteínas Virais/química , Proteínas Virais/imunologia , Internalização do Vírus , Liberação de Vírus/genética , Liberação de Vírus/imunologia , Replicação Viral/genética , Replicação Viral/imunologia
19.
Front Immunol ; 12: 810047, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35003140

RESUMO

Infection with the novel coronavirus, SARS-CoV-2, results in pneumonia and other respiratory symptoms as well as pathologies at diverse anatomical sites. An outstanding question is whether these diverse pathologies are due to replication of the virus in these anatomical compartments and how and when the virus reaches those sites. To answer these outstanding questions and study the spatiotemporal dynamics of SARS-CoV-2 infection a method for tracking viral spread in vivo is needed. We developed a novel, fluorescently labeled, antibody-based in vivo probe system using the anti-spike monoclonal antibody CR3022 and demonstrated that it could successfully identify sites of SARS-CoV-2 infection in a rhesus macaque model of COVID-19. Our results showed that the fluorescent signal from our antibody-based probe could differentiate whole lungs of macaques infected for 9 days from those infected for 2 or 3 days. Additionally, the probe signal corroborated the frequency and density of infected cells in individual tissue blocks from infected macaques. These results provide proof of concept for the use of in vivo antibody-based probes to study SARS-CoV-2 infection dynamics in rhesus macaques.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Imunofluorescência/métodos , SARS-CoV-2/crescimento & desenvolvimento , Replicação Viral/fisiologia , Animais , COVID-19/patologia , Linhagem Celular , Modelos Animais de Doenças , Humanos , Pulmão/patologia , Pulmão/virologia , Macaca mulatta , Estudo de Prova de Conceito , Glicoproteína da Espícula de Coronavírus/imunologia , Carga Viral/métodos
20.
PLoS One ; 15(11): e0241583, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33151959

RESUMO

PURPOSE: Alcohol concentration has traditionally been labeled in the form of alcohol by volume (ABV). This format can cause difficulty in evaluating accuracy of a pour because it doesn't directly connect with recommendations related to "standard drinks," the approach used by the US CDC and others organizations which intend to facilitate responsible drinking behaviors. Strategies which more directly connect guidelines related to healthy drinking behaviors to alcohol labeling are needed. OBJECTIVE: Assess how a label identifying the number of standard drinks per container impacts the ability of undergraduate students to accurately pour a standard drink. DESIGN: This study employed a 3 x 2 x 2 experimental design. Undergraduates were asked to pour a standard drink from mock products from three alcohol categories (beer, wine and liquor); products were presented in two types of label (traditional ABV vs. standard drinks/container) at two concentrations of alcohol content (high and low). RESULTS: We calculated standardized pour errors (pour errors in standard drink units). Analysis of these standardized pour errors suggested that 1) people tended to underpour beverages of low concentration across product categories and overpour those high in concentration. 2) When the standard drink label was present, pour accuracy was improved, when compared with pours from containers affixed with ABV labels in low alcohol concentrations across all product categories (beer, wine and liquor). 3) For treatments that comprised high concentrations of alcohol, the standard drink label significantly increased accuracy only for beer. However, it is worth noting that beer with an ABV label was the condition with the most dramatic overpours, and these problematic overpours were dramatically reduced by the addition of a standard drink label. CONCLUSIONS: Our work empirically supports the notion that Undergraduate students are better able to accurately assess and pour a standard drink of alcohol from bottles incorporating a label which includes standard drinks/container vs. those with traditional ABV labeling. That said, the effect is quite different for each alcohol category: beer, wine, and liquor and depends on whether the product is high or low in concentration of alcohol for its category; as such, policy makers should consider alcohol categories and concentrations from a public health perspective when recommending changes to labeling.


Assuntos
Bebidas Alcoólicas , Pesquisa Empírica , Rotulagem de Produtos , Estudantes , Universidades , Consumo de Bebidas Alcoólicas/epidemiologia , Humanos , Estados Unidos/epidemiologia
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