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BACKGROUND: Malignant clones of primary cutaneous T-cell lymphomas (CTCL) can show a CD4, CD8 or TCR-γδ phenotype, but their individual impact on tumor biology and skin lesion formation remains ill-defined. OBJECTIVES: To perform a comprehensive molecular characterization of CD4+ vs. CD8+ and TCR-γ/δ+ CTCL lesions. METHODS: We performed scRNA-seq of 18 CTCL skin biopsies to compare classic CD4+ advanced-stage mycosis fungoides (MF) with TCR-γ/δ+MF and primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (Berti's lymphoma). RESULTS: Malignant clones of TCR-γ/δ+MF and Berti's lymphoma showed similar clustering patterns distinct from CD4+MF, along with increased expression of cytotoxic markers such as NKG7, CTSW, GZMA, and GZMM. Only advanced-stage CD4+MF clones expressed central memory T-cell markers (SELL, CCR7, LEF1), alongside B1/B2 blood involvement, whereas TCR-γ/δ+MF and Berti's lymphoma harbored a more tissue-resident phenotype (CD69, CXCR4, NR4A1) without detectable cells in the blood. CD4+MF and TCR-γ/δ+MF skin lesions harbored strong type 2 immune activation across myeloid cells, while Berti's lymphoma was more skewed towards type 1 immune responses. Both CD4+MF and TCR-γ/δ+MF lesions showed upregulation of keratinocyte hyperactivation markers such as S100As and KRT16 genes. This increase was entirely absent in Berti's lymphoma, possibly reflecting an aberrant keratinocyte response to invading tumor cells, that could contribute to the formation of the typical ulcero-necrotic lesions within this entity. CONCLUSIONS: Our scRNAseq profiling study reveals specific molecular patterns associated with distinct CTCL subtypes.
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Outer membrane vesicles (OMVs) of Gram-negative bacteria have been studied intensively in recent years, primarily in their role in delivering virulence factors and antigens during pathogenesis. However, the near ubiquity of their production suggests that they may play other roles, such as responding to envelope stress or trafficking various cargoes to prevent dilution or degradation by other bacterial species. Here we show that OMVs produced by Xylella fastidiosa, a xylem-colonizing plant pathogenic bacterium, block its interaction with various surfaces such as the walls of xylem vessels in host plants. The release of OMVs was suppressed by the diffusible signal factor-dependent quorum-sensing system, and a X. fastidiosa ΔrpfF mutant in which quorum signaling was disrupted was both much more virulent to plants and less adhesive to glass and plant surfaces than the WT strain. The higher virulence of the ΔrpfF mutant was associated with fivefold higher numbers of OMVs recovered from xylem sap of infected plants. The frequency of attachment of X. fastidiosa to xylem vessels was 20-fold lower in the presence of OMVs than in their absence. OMV production thus is a strategy used by X. fastidiosa cells to adjust attachment to surfaces in its transition from adhesive cells capable of insect transmission to an "exploratory" lifestyle for systemic spread within the plant host which would be hindered by attachment. OMV production may contribute to the movement of other bacteria in porous environments by similarly reducing their contact with environmental constituents.
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Aderência Bacteriana , Membrana Celular/metabolismo , Vesículas Secretórias/metabolismo , Vitis/microbiologia , Xylella/patogenicidade , Adesividade , Proteínas de Bactérias/metabolismo , Membrana Celular/ultraestrutura , Modelos Biológicos , Mutação/genética , Nanopartículas/ultraestrutura , Doenças das Plantas/microbiologia , Vesículas Secretórias/ultraestrutura , Propriedades de Superfície , Xylella/ultraestruturaRESUMO
The slots model of visual working memory, despite its simplicity, has provided an excellent account of data across a number of change detection experiments. In the current research, we provide a new test of the slots model by investigating its ability to account for the increased prevalence of errors when there is a potential for confusion about the location in which items are presented during study. We assume that such location errors in the slots model occur when the feature information for an item in one location is swapped with the feature information for an item in another location. We show that such a model predicts two factors that will influence the extent to which location errors occur: (1) whether the test item changes to an "external" item not presented at study, or to an "internal" item presented at another location during study, and (2) the number of items in the study array. We manipulate these factors in an experiment, and show that the slots model with location errors fails to provide a satisfactory account of the observed data.
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Memória de Curto Prazo/fisiologia , Modelos Psicológicos , Desempenho Psicomotor/fisiologia , Percepção Espacial/fisiologia , Percepção Visual/fisiologia , Adulto , Humanos , Adulto JovemRESUMO
We compared the effectiveness of different encoding techniques across the adult age range. Three hundred participants: 100 younger, 100 middle-aged, and 100 older adults, were asked to encode a set of visually presented concrete and abstract words. Participants were shown target words one at a time, along with prompts (randomly and intermixed, within-subject) to either silently read, read aloud, write, or draw a picture of the target, for a duration of 10-seconds each. On a later free recall test, participants were given 2-minutes to type all the words they could remember from the encoding phase. Across age groups, we showed that drawing, writing, and reading aloud as encoding techniques yielded better memory than silently reading words, with drawing leading to the largest boost. While memory performance did decrease as age increased, it interacted with the encoding technique. Of note, there were no differences in memory performance in middle-aged compared to young adults. Importantly, age differences in memory emerged only when drawing was used as the encoding strategy, in line with previously reported age-related deficits in generating imagery, or integrating it with motoric processes. Despite this, concrete relative to abstract words that were drawn or written during encoding were better retained, regardless of age, suggesting these techniques facilitate formation of age-invariant visuo-spatial representations. Our findings suggest that whether age differences in memory emerge depends on the strategy used at encoding, and the type of information being encoded.
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Rememoração Mental , Redação , Idoso , Humanos , Pessoa de Meia-Idade , Cognição , Leitura , Adulto JovemRESUMO
Drawing at encoding has been shown to improve later recall of to-be-remembered words, pictures, and academic terms, compared to when one simply writes out the target information. Here we examined whether drawing in a diary, compared to writing in it, differentially improved later memorability of personal autobiographical events, and whether aging influenced the magnitude of this effect. Thirty younger and thirty older adults were given a diary booklet, and instructed to use it to reminisce about a random daily event of their choosing, on 12 days within a two-week period. They recorded the event on each day in one of two ways, counterbalanced within-subject: by writing about or by drawing a picture of the event. Participants also generated a keyword descriptor for each event. After the two-week period, participants were cued using their keyword descriptors to recall each autobiographical memory by writing it down. Self-reported match accuracy, between reminisced and recalled events was tabulated. Across age groups, match accuracy was significantly higher for those drawn than written during the reminiscing phase. In addition, we compared the word count, level of detail, visual imagery, and point of view of the recalled memories. Self-reports of the level of detail in the recalled memory were better maintained for events drawn compared to written during the reminiscing stage, and better maintained in older than younger adults. Our findings suggest the use of drawing, while reminiscing within a diary format, enhances accuracy and quality of later recollections.
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Memória Episódica , Humanos , Idoso , Rememoração Mental , Envelhecimento/psicologia , Redação , Sinais (Psicologia)RESUMO
Past work has demonstrated that drawing a sketch, compared to writing during encoding, improves memory of to-be-remembered words, pictures, and academic terms. We examined whether this benefit extended to emotional materials. In Experiment 1, negative, positive, and neutral words were presented in an encoding phase, with intermixed prompts to either write out or draw a picture representing the word. Participants later freely recalled words by writing them out. Recall was higher for words drawn than for words written at encoding, and the magnitude of the benefit was differentially enhanced for emotional compared to neutral words. In Experiment 2, negative, positive, and neutral words were again presented but encoding type was compared using pure lists between participants. The pattern of memory performance replicated that observed in Experiment 1. Further, the use of drawing as an encoding technique interacted with emotionality, whereby emotional words that were drawn were best remembered. Our results demonstrate that the memory benefit conferred by drawing at encoding extends to emotional materials. Our findings suggest that the use of drawing as an encoding strategy, and the emotionality of the stimulus itself, contributes independently to enhance retention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Emoções , Rememoração Mental , Humanos , CogniçãoRESUMO
OBJECTIVE: Work-family conflict has been shown to adversely affect individuals' health and function, particularly among individuals with chronic pain. The current study's longitudinal serial mediation model examined whether work-to-family conflict predicted greater pain interference through higher levels of family strain and loneliness among midlife adults with chronic pain. METHODS AND MEASURES: The study consisted of 303 participants from two waves of the national longitudinal study of Midlife in the United States (MIDUS) at wave II from 2004 to 2006 (Mage = 57, SD = 11) and wave 3 from 2013 to 2014 (Mage = 66, SD = 11). Participants were employed at time 1 and had chronic pain at both time points, and 54.5% of participants identified as female. RESULTS: Family strain at time 1 (T1) and loneliness at time 2 (T2), respectively, significantly mediated the association of work-to-family conflict (T1) on pain interference at T2. Participants with greater work-to-family conflict perceived more family strain, felt lonelier, and, in turn, reported experiencing higher interference from chronic pain. CONCLUSION: Results suggest that unmanaged work-to-family conflict could be a risk factor that exacerbates chronic pain symptoms through worsening family relationships and loneliness among midlife adults with chronic pain.
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Transgene driven expression of Escherichia coli nitroreductase (NTR1.0) renders animal cells susceptible to the antibiotic metronidazole (MTZ). Many NTR1.0/MTZ ablation tools have been reported in zebrafish, which have significantly impacted regeneration studies. However, NTR1.0-based tools are not appropriate for modeling chronic cell loss as prolonged application of the required MTZ dose (10â mM) is deleterious to zebrafish health. We established that this dose corresponds to the median lethal dose (LD50) of MTZ in larval and adult zebrafish and that it induced intestinal pathology. NTR2.0 is a more active nitroreductase engineered from Vibrio vulnificus NfsB that requires substantially less MTZ to induce cell ablation. Here, we report on the generation of two new NTR2.0-based zebrafish lines in which acute ß-cell ablation can be achieved without MTZ-associated intestinal pathology. For the first time, we were able to sustain ß-cell loss and maintain elevated glucose levels (chronic hyperglycemia) in larvae and adults. Adult fish showed significant weight loss, consistent with the induction of a diabetic state, indicating that this paradigm will allow the modeling of diabetes and associated pathologies.
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Diabetes Mellitus , Hiperglicemia , Animais , Peixe-Zebra/metabolismo , Hiperglicemia/complicações , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Nitrorredutases/metabolismo , Animais Geneticamente ModificadosRESUMO
Introduction: Self-management education and support (SMES) programs can prevent adverse chronic disease outcomes, but factors modifying their reception remain relatively unexplored. We examined how perceptions of an SMES program were influenced by the mode of delivery, and co-receipt of a paired financial benefit. Methods and Patients: Using a cross-sectional survey, we evaluated the perceived helpfulness of a SMES program among 446 low-income seniors at high risk for cardiovascular events in Alberta, Canada. Secondary outcomes included frequency of use, changes in perspectives on health, satisfaction with the program, and comprehensibility of the material. Participants received surveys after engaging with the program for at least 6 months. We used modified Poisson regression to calculate relative risks. Open-ended questions were analyzed inductively. Results: The majority of participants reported that the SMES program was helpful (>80%). Those who also received the financial benefit (elimination of medication copayments) were more likely to report that the SMES program was helpful (RR 1.24, 95% CI 1.11-1.39). Those who received the program electronically were more likely to use the program weekly (RR 1.51, 1.25-1.84). Both those who received the intervention electronically (RR 1.18, 1.06-1.33), and those who also received copayment elimination (RR 1.17, 1.05-1.31) were more likely to state that the program helped change their perspectives on health. Conclusion: When designing SMES programs, providing the option for electronic delivery appears to promote greater use for seniors. The inclusion of online-delivery and co-receipt of tangible benefits when designing an SMES program for seniors results in favorable reception and could facilitate sustained adherence to health behavior recommendations. Participants also specifically expressed that what they enjoyed most was that the SMES program was informative, helpful, engaging, and supportive.
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BACKGROUND: The ability to flexibly enhance and suppress emotional expressions plays an important role in emotion regulation and the fostering of social connections. Deficits in expressive flexibility have been linked with posttraumatic stress disorder and prolonged grief reactions. Previous studies have suggested that the ability to respond flexibly in the context of an immediate threat (a nonconscious prime) may be important. In this study we sought to extend this work by examining the impact of individual differences in anxiety on expressive flexibility. METHODS: Eighty four participants with high and low trait anxiety viewed blocks of negative images with instructions to enhance or suppress emotional expressions. Across blocks one of three nonconscious primes (threat, safety, neutral) appeared before each image. Observers blind to the study's design rated participants' emotional expressiveness. RESULTS: Repeated Measures Anova's showed that high trait anxiety was associated with lower levels in enhancement ability. Further, low trait anxiety was associated with less emotion in response to the threat prime irrespective of expressive instruction. LIMITATIONS: This study was cross-sectional which precludes causal relationships. Participants were drawn from a student population and the generalizability to other populations will need to be established CONCLUSIONS: This study identified trait anxiety as factor that may contribute to expressive flexibility deficits. High trait anxiety is a feature of many clinical conditions. Strategies to target expressive flexibility may relevant to a range of anxiety related clinical conditions.
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Ansiedade , Transtornos de Estresse Pós-Traumáticos , Transtornos de Ansiedade , Estudos Transversais , Emoções , HumanosRESUMO
OBJECTIVE: To assess whether medication use, specifically statin, metformin, and aspirin, affects the growth of vestibular schwannomas (VSs). STUDY DESIGN: Retrospective case series. SETTING: Single tertiary care academic hospital. SUBJECTS AND METHODS: Patients were enrolled if they were diagnosed with sporadic VS and had at least 2 magnetic resonance imaging (MRI) studies at a minimum of 6 months apart prior to any intervention. Electronic medical records were reviewed for demographic and medication data. Tumor volumes on MRI studies were assessed via BrainLab iPlan. The primary endpoint was VS tumor growth, defined as a 20% increase in tumor volume, between consecutive MRI studies or between the first and last available MRI study. Predictors of volumetric growth, specifically statin, aspirin, or metformin use, were analyzed with t tests, chi-square test, univariate logistic regression, and multivariate logistic regression. RESULTS: A total of 387 patients met inclusion criteria, 53.5% of whom were women. For all patients, the mean age was 60.6 years (range, 18.2-89.2 years); the mean axial tumor diameter, 11.9 mm (range, 1.7-32.0 mm); and the mean tumor volume, 0.85 cm3 (range, 0.01-13.1 cm3). In review of the electronic medical record, 46 patients (11.9%) were taking metformin; 145 (37.5%), a statin; and 117 (30.2%), aspirin. Among patients taking metformin, 39.1% (18/46) exhibited volumetric growth, as opposed to 58.2% (198/340) of nonusers (P = .014). Metformin (odds ratio, 0.497; P = .036) is significantly associated with reduced VS growth when controlling for aspirin, statin, and tumor size on multivariate logistic regression. CONCLUSION: Metformin use is associated with reduced volumetric VS growth.
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Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Neuroma Acústico/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/diagnóstico por imagem , Estudos Retrospectivos , Carga TumoralRESUMO
As data and recommendations regarding antibiotic prophylaxis in dermatologic surgery vary, we tried to describe the effect of antibiotic prophylaxis (AP) in Mohs micrographic surgery (MMS) on infective endocarditis, prosthetic joint infection, and surgical site infection using a single-institution retrospective cohort study of antibiotic use (pre-/intra-operative, post-operative or none) among 2,364 patient encouters treated with MMS. Bivariate logistic regression was evaluated for associations between patient and operative characteristics, antibiotic use, and infectious complications. 85.8% of patients received no AP, 10.0% received post-operative AP, and 4.1% received pre-/intra-operative AP. The overall surgical site infection (SSI) rate was 1.3%. SSI did not differ between patients who received pre-/intra-operative prophylaxis, post-operative prophylaxis or no antibiotics. One patient receiving pre-/intra-operative prophylaxis developed SSI. Repairs involving porcine xenografts and interpolation/pedicle flaps were associated with increased SSI. In addition, there were no patients who post-operatively experienced an infected joint or infective endocarditis. Limitations include selection bias, use of observational retrospective data, low infection rates, single institution analysis, and possible omission of explanatory variables or confounders. There was no difference in rates of SSI when comparing MMS patients who received pre-/intra-operative, post-operative or no AP. There were no cases of infective endocarditis or infected prosthetic joint.
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Antibacterianos/uso terapêutico , Antibioticoprofilaxia/estatística & dados numéricos , Endocardite/epidemiologia , Cirurgia de Mohs/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Idoso , Endocardite/etiologia , Endocardite/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controleRESUMO
OBJECTIVE: One of the most challenging parts of running clinical trials is recruiting enough participants. Our objective was to determine which recruitment strategies were effective in reaching specific subgroups. STUDY DESIGN AND SETTING: We assessed the efficacy and costs of the recruitment strategies used in the Assessing Outcomes of Enhanced Chronic Disease Care Through Patient Education and a Value-based Formulary Study (ACCESS) in Alberta, Canada. RESULTS: Twenty percent of the study budget ($354,330 CAD) was spent on recruiting 4013 participants, giving an average cost per enrolled of $88 CAD. Pharmacies recruited the most participants (n = 1217), at a cost of $128/enrolled. "Paid media" had the highest cost ($806/enrolled), whereas "word of mouth" and "unpaid media" had the lowest (~$3/enrolled). Participants enrolled from "seniors outreach" had the lowest baseline quality of life and income, while participants from "word of mouth" had the lowest educational attainment. CONCLUSION: The "health care providers" strategies were especially successful - at a moderate cost per enrolled. The "media" strategies were less effective, short lasting, and more costly. No strategy was singularly effective in recruiting our targeted groups, emphasizing the importance of utilizing a variety of strategies to reach recruitment goals. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02579655 . Registered on 19 October 2015.
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Orçamentos , Renda , Seleção de Pacientes , Pobreza , Ensaios Clínicos Pragmáticos como Assunto/economia , Sujeitos da Pesquisa , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alberta , Feminino , Humanos , Masculino , Tamanho da AmostraRESUMO
Low energy electron beam (LEEB) treatment is an emerging non-thermal technology that performs surface decontamination with a minimal influence on food quality. Bacterial spore resistance toward LEEB treatment and its influencing factors were investigated in this study. Spores from Geobacillus and Bacillus species were treated with a lab-scale LEEB at energy levels of 80 and 200 keV. The spore resistances were expressed as D-values (the radiation dose required for one log10 reduction at a given energy level) calculated from the linear regression of log10 reduction against absorbed dose of the sample. The results revealed that the spore inactivation efficiency by LEEB is comparable to that of other ionizing radiations and that the inactivation curves are mostly log10-linear at the investigated dose range (3.8 - 8.2 kGy at 80 keV; 6.0 - 9.8 kGy at 200 keV). The D-values obtained from the wildtype strains varied from 2.2 - 3.0 kGy at 80 keV, and from 2.2 - 3.1 kGy at 200 keV. Bacillus subtilis mutant spores lacking α/ß-type small, acid-soluble spore proteins showed decreased D-values (1.3 kGy at 80 and 200 keV), indicating that spore DNA is one of the targets for LEEB spore inactivation. The results revealed that bacterial species, sporulation conditions and the treatment dose influence the spore LEEB inactivation. This finding indicates that for the application of this emerging technology, special attention should be paid to the choice of biological indicator, physiological state of the indicator and the processing settings. High spore inactivation efficiency supports the application of LEEB for the purpose of food surface decontamination. With its environmental, logistical, and economic advantages, LEEB can be a relevant technology for surface decontamination to deliver safe, minimally processed and additive-free food products.
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Sequential effects are ubiquitous in decision-making, but no more than in the absolute identification task where participants must identify stimuli from a set of items that vary on a single dimension. A number of competing explanations for these sequential effects have been proposed, and recently Matthews and Stewart [(2009a). The effect of inter-stimulus interval on sequential effects in absolute identification. The Quarterly Journal of Experimental Psychology, 62, 2014-2029] showed that manipulations of the time between decisions is useful in discriminating between these accounts. We use a Bayesian hierarchical regression model to show that inter-trial interval has an influence on behaviour when it varies across different blocks of trials, but not when it varies from trial to trial. We discuss the implications of both our and Matthews and Stewart's results on the effect of inter-trial interval for theories of sequential effects.
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Atenção/fisiologia , Tomada de Decisões/fisiologia , Aprendizagem por Discriminação/fisiologia , Percepção do Tempo/fisiologia , Teorema de Bayes , Feminino , Humanos , Masculino , Estimulação Luminosa , Tempo de Reação/fisiologia , Análise de Regressão , Estudantes , Fatores de Tempo , UniversidadesRESUMO
A fundamental issue concerning visual working memory is whether its capacity limits are better characterized in terms of a limited number of discrete slots (DSs) or a limited amount of a shared continuous resource. Rouder et al. (2008) found that a mixed-attention, fixed-capacity, DS model provided the best explanation of behavior in a change detection task, outperforming alternative continuous signal detection theory (SDT) models. Here, we extend their analysis in two ways: first, with experiments aimed at better distinguishing between the predictions of the DS and SDT models, and second, using a model-based analysis technique called landscaping, in which the functional-form complexity of the models is taken into account. We find that the balance of evidence supports a DS account of behavior in change detection tasks but that the SDT model is best when the visual displays always consist of the same number of items. In our General Discussion section, we outline, but ultimately reject, a number of potential explanations for the observed pattern of results. We finish by describing future research that is needed to pinpoint the basis for this observed pattern of results.
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Atenção/fisiologia , Memória de Curto Prazo/fisiologia , Detecção de Sinal Psicológico/fisiologia , Humanos , Modelos Teóricos , Estimulação Luminosa/métodos , Desempenho Psicomotor/fisiologia , Curva ROC , Percepção Visual/fisiologiaRESUMO
OBJECTIVE: To explore pharmacist-consumer interactions around the use of complementary medicines (CMs), with specific focus on consumer expectations, perceptions and satisfaction. METHODS: Twenty pharmacists and 20 healthcare consumers were recruited across 16 metropolitan community pharmacies in Adelaide, Australia, from June to August 2011. Semi-structured interviews containing comparable questions for both study groups were used. Data was transcribed and analysed with the aid of AutoMap®. KEY FINDINGS: There was high consumer satisfaction with pharmacists as CM providers, which was in agreement with pharmacist's perceptions of consumer satisfaction. However, this was against a background of low consumer expectations and pharmacists' dissatisfaction with their own role in the interaction. Consumers often perceived pharmacy-stocked CMs to be more effective and safer compared to those in supermarkets or health food shops, but this perception was not shared by pharmacists. Pharmacists believed they had significant influence around recommendation and use of CMs, whereas consumers perceived a more limited influence. Both pharmacists and consumers shared similar perceptions of CM safety and similar expectations regarding business influence and professional pressures on information provision. CONCLUSION: Behind a perception of high satisfaction, consumers have low expectations of pharmacists around provision of CM-related information. Further work is required to improve pharmacists' knowledge and confidence around CM use and to address barriers such as the tension between potentially competing business pressures and professional responsibilities.