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BACKGROUND: Although research participants are generally interested in receiving results from studies in which they participate, health researchers rarely communicate study findings to participants. The present study was designed to provide opportunity for a broad group of health researchers to describe their experiences and concerns related to sharing results (i.e. aggregate study findings) with research participants. METHODS: We used a mixed-methods concurrent triangulation design, relying on an online survey to capture health researchers' experiences, perceptions and barriers related to sharing study results with participants. Respondents were health researchers who conduct research that includes the consent of human subjects and hold a current appointment at an accredited academic medical institution within the United States. For quantitative data, the analytic strategy focused on item-level descriptive analyses. For the qualitative data, analyses focused on a priori themes and emergent subthemes. RESULTS: Respondents were 414 researchers from 44 academic medical institutions; 64.5% reported that results should always be shared with participants, yet 60.8% of respondents could identify studies in which they had a leadership role where results were not shared. Emergent subthemes from researchers' reasons why results should be shared included participant ownership of findings and benefits of results sharing to science. Reasons for not sharing included concerns related to participants' health literacy and participants' lack of desire for results. Across all respondents who described barriers to results sharing, the majority described logistical barriers. CONCLUSIONS: Study findings contribute to the literature by documenting researchers' perspectives and experiences about sharing results with research participants, which can inform efforts to improve results sharing. Most respondents indicated that health research results should always be shared with participants, although the extent to which many respondents described barriers to results sharing as well as reported reasons not to share results suggests difficulties with a one-size-fits-all approach to improving results sharing.
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Atitude , Pesquisa Biomédica , Revelação , Disseminação de Informação , Pesquisadores , Sujeitos da Pesquisa , Comunicação , Humanos , Inquéritos e Questionários , Estados UnidosRESUMO
In this study we examined attention-related reaction time (RT) and intra-individual variability (IIV) in younger and older adults using an iPad-based visual search test, in which, for each trial, participants were required to sequentially press a series of on-screen stimuli numbered from 1 to 8. Although overall performance RT was significantly slower, with greater IIV for the older compared to the younger adult group, there was also a disproportionately slowed RT and greater IIV for the first item in the series compared to all other responses within the trial. When the response to the first stimulus was removed from statistical analysis, the significant age-related RT slowing effect remained, but IIV was no longer significantly greater for the older compared to the younger adults. This pattern of results reveals a dichotomy between the preservation of RT and IIV in aging, and one that is strongly related to research methodology. A finding that may account, at least in part, for the outcome heterogeneity in the study of IIV in aging.
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Variação Biológica Individual , Processamento Eletrônico de Dados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Tempo de Reação/fisiologia , Adulto JovemRESUMO
BACKGROUND: Studies have demonstrated that patients with primary prevention implantable cardioverter-defibrillators (ICDs) often misunderstand the ICD. Advances in behavioral economics demonstrate that some misunderstandings may be due to cognitive biases. We aimed to explore the influence of cognitive bias on ICD decision making. METHODS AND RESULTS: We used a qualitative framework analysis including 9 cognitive biases: affect heuristic, affective forecasting, anchoring, availability, default effects, halo effects, optimism bias, framing effects, and state dependence. We interviewed 48 patients from 4 settings in Denver. The majority were male (n = 32). Overall median age was 61 years. We found frequent evidence for framing, default, and halo effects; some evidence of optimism bias, affect heuristic, state dependence, anchoring and availability bias; and little or no evidence of affective forecasting. Framing effects were apparent in overestimation of benefits and downplaying or omitting potential harms. CONCLUSIONS: We found evidence of cognitive bias in decision making for ICD implantation. The majority of these biases appeared to encourage ICD treatment.
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Cognição , Tomada de Decisões , Desfibriladores Implantáveis/psicologia , Insuficiência Cardíaca/psicologia , Insuficiência Cardíaca/cirurgia , Pesquisa Qualitativa , Adulto , Idoso , Desfibriladores Implantáveis/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: People with end-stage heart failure may have to decide about destination-therapy left ventricular assist device (DT-LVAD). Individuals facing difficult decisions often rely on heuristics, such as anchoring, which predictably bias decision outcomes. We aimed to investigate whether showing a larger historical Heartmate XVE creates an anchoring effect, making the smaller Heartmate II (HMII) appear more favorable. METHODS: With the use of Amazon Mechanical Turk, participants watched videos asking them to imagine themselves dying of end-stage heart failure, then were presented the option of LVAD as potentially life-prolonging therapy. Participants were randomized to a control group who were only shown the HMII device, and the intervention group who saw the XVE device before the HMII. Participants then completed surveys. RESULTS: A total of 487 participants completed the survey (control = 252; intervention = 235); 79% were <40 years of age, 84% were white, and 55% were male. The intervention group was not more likely to accept the LVAD therapy (68% vs 61%; P = .37). However, participants in the intervention group were more likely (51% vs 17%; P < .01) to agree or strongly agree with the statement that the HMII was "smaller than expected." Participants in the intervention group were also more likely to rate the size of the device as "important" or "very important" in their decision (61% vs 46%; P < .01). CONCLUSIONS: Although the XVE anchor did not affect likelihood of accepting the LVAD, it did affect device perception. This article highlights an important point with clinical implications: factors such as anchoring have the potential to inappropriately influence perceptions and decisions and should be carefully considered in research and practice.
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Tomada de Decisões , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Educação de Pacientes como Assunto/métodos , Adulto , Fatores Etários , Idoso , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Participação do Paciente/estatística & dados numéricos , Desenho de Prótese , Valores de Referência , Fatores de Risco , Fatores Sexuais , Estados Unidos , Gravação em Vídeo , Adulto JovemRESUMO
BACKGROUND: When patients are not adequately engaged in decision making, they may be at risk of decision regret. Our objective was to explore patients' perceptions of their decision-making experiences related to implantable cardioverter defibrillators (ICDs). METHODS: Cross-sectional, mailed survey of 412 patients who received an ICD without cardiac resynchronization therapy for any indication between 2006 and 2009. Patients were asked about decision participation and decision regret. RESULTS: A total of 295 patients with ICDs responded (72% response rate). Overall, 79% reported that they were as involved in the decision as they wanted. However, 28% reported that they were not told of the option of not getting an ICD and 37% did not remember being asked if they wanted an ICD. In total, 19% reported not wanting their ICD at the time of implantation. Those who did not want the ICD were younger (<65 years; 74% vs 43%, P < 0.001), had higher decision regret (31/100 vs 11/100, P < 0.001), and reported less participation in decision making (the doctor "totally" made the decision, 9% vs 3%; P < 0.001). CONCLUSIONS: A considerable number of ICD recipients recalled not wanting their ICD at the time of implantation. While these findings may be prone to recall bias, they likely identify opportunities to improve ICD decision making.
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Desfibriladores Implantáveis , Participação do Paciente , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Alpha-toxin is a major Staphylococcus aureus virulence factor. This study evaluated potential relationships between in vitro alpha-toxin expression of S. aureus bloodstream isolates, anti-alpha-toxin antibody in serum of patients with S. aureus bacteremia (SAB), and clinical outcomes in 100 hemodialysis and 100 postsurgical SAB patients. Isolates underwent spa typing and hla sequencing. Serum anti-alpha-toxin IgG and neutralizing antibody levels were measured by using an enzyme-linked immunosorbent assay and a red blood cell (RBC)-based hemolysis neutralization assay. Neutralization of alpha-toxin by an anti-alpha-toxin monoclonal antibody (MAb MEDI4893) was tested in an RBC-based lysis assay. Most isolates encoded hla (197/200; 98.5%) and expressed alpha-toxin (173/200; 86.5%). In vitro alpha-toxin levels were inversely associated with survival (cure, 2.19 µg/ml, versus failure, 1.09 µg/ml; P < 0.01). Both neutralizing (hemodialysis, 1.26 IU/ml, versus postsurgical, 0.95; P < 0.05) and IgG (hemodialysis, 1.94 IU/ml, versus postsurgical, 1.27; P < 0.05) antibody levels were higher in the hemodialysis population. Antibody levels were also significantly higher in patients infected with alpha-toxin-expressing S. aureus isolates (P < 0.05). Levels of both neutralizing antibodies and IgG were similar among patients who were cured and those not cured (failures). Sequence analysis of hla revealed 12 distinct hla genotypes, and all genotypic variants were susceptible to a neutralizing monoclonal antibody in clinical development (MEDI4893). These data demonstrate that alpha-toxin is highly conserved in clinical S. aureus isolates. Higher in vitro alpha-toxin levels were associated with a positive clinical outcome. Although patients infected with alpha-toxin-producing S. aureus exhibited higher anti-alpha-toxin antibody levels, these levels were not associated with a better clinical outcome in this study.
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Anticorpos Antibacterianos/imunologia , Bacteriemia , Toxinas Bacterianas/genética , Expressão Gênica , Variação Genética , Proteínas Hemolisinas/genética , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antibacterianos/uso terapêutico , Anticorpos Antibacterianos/sangue , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Toxinas Bacterianas/imunologia , Feminino , Genótipo , Proteínas Hemolisinas/imunologia , Hemólise/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Coelhos , Diálise Renal/efeitos adversos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/classificação , Falha de Tratamento , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The study aimed to gain insight into the experiences of patients with cancer and survivors regarding the integration of social needs assessment into their care, while also gathering perspectives from patient navigators on the barriers to obtaining and utilizing social needs information during cancer care, which taken together may influence cancer care policies. By comparing the perspectives of patients and navigators, the study sought to inform best practices for integrating, identifying, and addressing social needs to improve patient experiences and outcomes. METHODS: We conducted qualitative interviews and self-report surveys involving patients with cancer, providers, and patient navigators or care coordinators, seeking their insights and firsthand experiences related to health-related social needs in cancer care. Interviews were transcribed, separated into memos of main themes based on deductive coding, and further analyzed for new emergent themes using inductive coding. RESULTS: The present analysis focuses solely on the perspectives of 20 patient navigators and 21 patients. Qualitative analyses revealed two overarching themes: Theme 1: Personal and health system-related factors may create barriers for patients to disclose health-related social needs information during cancer care; and Theme 2: When social needs are identified, it is best practice to acknowledge and address social needs through referrals, resources, timely follow-up, and continued care coordination. Key barriers include individual beliefs and attitudes, concerns regarding privacy and sensitivity of questions, uncertainties about the outcomes of disclosing information, and patient-provider relationships and trust. CONCLUSION: Drawing upon the perspectives of patients and patient navigators provided valuable insight into the challenges associated with acquiring information on social needs. Their viewpoints presented feasible solutions to overcome barriers through early acknowledgment of patient needs, timely resource provision, and maintaining consistent follow-up actions. Additionally, it enhanced understanding of the pivotal role patient navigators play in oncology, serving as crucial links between screening for health-related social needs and addressing individual patient requirements. POLICY SUMMARY: The policies and policy improvements our paper seeks to impact include: inequalities in cancer care and health-related social needs of cancer.
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Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT), as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the LT-responsive CAST/Ei strain introgressed on a LT-resistant C57BL/6 (B6) background was screened for response to LT. Three congenic strains containing CAST/Ei regions of chromosome 11 were identified that displayed a rapid inflammatory response to LT similar to, but more severe than that driven by a LT-responsive allele of the inflammasome constituent NRLP1B. Importantly, increased response to LT in congenic mice correlated with greater resistance to infection by the Sterne strain of B. anthracis. The genomic region controlling the inflammatory response to LT was mapped to 66.36-74.67 Mb on chromosome 11, a region that encodes the LT-responsive CAST/Ei allele of Nlrp1b. However, known downstream effects of NLRP1B activation, including macrophage pyroptosis, cytokine release, and leukocyte infiltration could not fully explain the response to LT or the resistance to B. anthracis Sterne in congenic mice. Further, the exacerbated response in congenic mice is inherited in a recessive manner while the Nlrp1b-mediated response to LT is dominant. Finally, congenic mice displayed increased responsiveness in a model of sepsis compared with B6 mice. In total, these data suggest that allelic variation of one or more chromosome 11 genes in addition to Nlrp1b controls the severity of host response to multiple inflammatory stimuli and contributes to resistance to B. anthracis Sterne. Expression quantitative trait locus analysis revealed 25 genes within this region as high priority candidates for contributing to the host response to LT.
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Alelos , Antraz/genética , Bacillus anthracis , Cromossomos de Mamíferos/genética , Variação Genética , Imunidade Inata/genética , Animais , Antraz/imunologia , Antígenos de Bactérias/imunologia , Toxinas Bacterianas/imunologia , Cromossomos de Mamíferos/imunologia , Inflamação/genética , Inflamação/imunologia , Camundongos , Locos de Características Quantitativas/imunologiaRESUMO
A transposon insertional mutagenesis spore library of the pathogen Bacillus anthracis was screened to identify mutants altered in germination kinetics. One mutant exhibited an accelerated rate of germination in association with disruption of benK. This gene encodes a putative protein with high homology to membrane transporters that facilitate benzoate transport. We hypothesized that BenK may not be only spore associated, but also have a vegetative cell role. A reporter strain with a translational fusion of benK to green fluorescent protein demonstrated that full-length BenK was present in vegetative cells and that a BenK degradation product was present in spores by detecting the reporter using fluorescence and Western blot analysis. A minimum inhibitory concentration assay indicated that vegetative cells of a benK::Kan mutant were more susceptible to the antimicrobial effects of Na-benzoate. The mutant spores germinated to a greater extent within 1 h than the wild type in an in vitro fluorescence assay. The disruption of benK also resulted in spores that were less readily phagocytosed in a macrophage assay. Despite these altered in vitro phenotypes, no apparent effect of the BenK protein on virulence in the intranasal mouse model or the guinea pig competitive assay was observed. This work shows that, although the BenK protein does not impact fitness or virulence in an infection model, it is involved in other aspects of both the spore and vegetative forms of the organism.
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Bacillus anthracis/fisiologia , Proteínas de Bactérias/genética , Fenótipo , Esporos Bacterianos , Antibacterianos/farmacologia , Bacillus anthracis/efeitos dos fármacos , Bacillus anthracis/patogenicidade , Aptidão Genética , Macrófagos/imunologia , Macrófagos/microbiologia , Testes de Sensibilidade Microbiana , Mutação , Fagocitose/genética , Fagocitose/imunologia , VirulênciaRESUMO
Pathogenesis of Bacillus anthracis is associated with the production of lethal toxin (LT), which activates the murine Nalp1b/Nlrp1b inflammasome and induces caspase-1-dependent pyroptotic death in macrophages and dendritic cells. In this study, we investigated the effect of allelic variation of Nlrp1b on the outcome of LT challenge and infection by B. anthracis spores. Nlrp1b allelic variation did not alter the kinetics or pathology of end-stage disease induced by purified LT, suggesting that, in contrast to previous reports, macrophage lysis does not contribute directly to LT-mediated pathology. However, animals expressing a LT-sensitive allele of Nlrp1b showed an early inflammatory response to LT and increased resistance to infection by B. anthracis. Data presented here support a model whereby LT-mediated activation of Nlrp1b and subsequent lysis of macrophages is not a mechanism used by B. anthracis to promote virulence, but rather a protective host-mediated innate immune response.
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Antraz/genética , Antraz/imunologia , Proteínas Reguladoras de Apoptose/genética , Predisposição Genética para Doença , Animais , Antígenos de Bactérias/toxicidade , Bacillus anthracis/imunologia , Bacillus anthracis/patogenicidade , Toxinas Bacterianas/toxicidade , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos TransgênicosRESUMO
OBJECTIVE: Latina college women are at risk for eating disorders (EDs), but assessment is problematic, because the psychometric properties of risk factor measures have not been evaluated with this group. METHOD: Reliability and validity estimates of the Eating Disorder Examination Questionnaire, Body Esteem Scale, Sociocultural Attitudes Toward Appearance Questionnaire-3, and Body Shape Questionnaire were examined in a sample of 173 female Latina college students. RESULTS: Cronbach α coefficients (.75-.96) and intraclass coefficients (.65-.96) indicated good reliability. Most measures were significantly correlated, providing evidence for convergent validity. Confirmatory factor analyses resulted in good fit indices. DISCUSSION: These findings indicate that commonly used measures of ED risk have adequate reliability and validity in Latina college women. Comparison data suggest that ED risk may be similar or even higher in Latina college women relative to Caucasian college women. Prevention efforts with diverse groups are needed.
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Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Hispânico ou Latino/psicologia , Mulheres/psicologia , Adolescente , Imagem Corporal , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Humanos , Psicometria , Reprodutibilidade dos Testes , Risco , Autoimagem , Estudantes/psicologia , Inquéritos e Questionários , Universidades , Adulto JovemRESUMO
Bacillus anthracis, the etiological agent of anthrax, is a spore-forming, Gram-positive bacterium and a category A biothreat agent. Screening of a library of transposon-mutagenized B. anthracis spores identified a mutant displaying an altered phenotype that harbored a mutated gene encoding the purine biosynthetic enzyme PurH. PurH is a bifunctional protein that catalyzes the final steps in the biosynthesis of the purine IMP. We constructed and characterized defined purH mutants of the virulent B. anthracis Ames strain. The virulence of the purH mutants was assessed in guinea pigs, mice, and rabbits. The spores of the purH mutants were as virulent as wild-type spores in mouse intranasal and rabbit subcutaneous infection models but were partially attenuated in a mouse intraperitoneal model. In contrast, the purH mutant spores were highly attenuated in guinea pigs regardless of the administration route. The reduced virulence in guinea pigs was not due solely to a germination defect, since both bacilli and toxins were detected in vivo, suggesting that the significant attenuation was associated with a growth defect in vivo. We hypothesize that an intact purine biosynthetic pathway is required for the virulence of B. anthracis in guinea pigs.
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Antraz/microbiologia , Bacillus anthracis/metabolismo , Bacillus anthracis/patogenicidade , Purinas/biossíntese , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Cobaias , Camundongos , Coelhos , Fatores de Tempo , VirulênciaRESUMO
BACKGROUND: Subjective cognitive decline (SCD) is increasingly recognized in both the clinical and research arenas as a risk factor for mild cognitive impairment (MCI) and dementia. Although SCD is etiologically heterogeneous and potentially treatable, in comparison to MCI and Alzheimer's disease, SCD remains poorly characterized with its clinical relevance often questioned. OBJECTIVE: This study's aim was to improve the characterization of SCD within the general public. METHODS: Individuals with SCD were compared to those without via a battery of measures. RESULTS: Both the SCD and the non-SCD group correlational analysis identified significant relationships between worse SCD, worse metacognitive dysfunction, negative affective symptoms, and greater levels of stress. The SCD group displayed additional correlational relationships between Cognitive Change Index (Self report) (CCI-S) scores, higher neuroticism scores, and poorer quality of life (QoL). Partial correlation analysis in the SCD group suggests CCI-S scores, anxiety, depression, and metacognition are intercorrelated. Ad hoc analyses using metacognition as the grouping variable found that those experiencing worse metacognitive dysfunction were significantly more likely to experience poorer SCD, psychological and social QoL, greater levels of anxiety, depression, stress, and neuroticism. CONCLUSION: The emerging pattern from the analysis indicates that SCD appears associated with sub-clinical negative affective difficulties, metacognitive, and other psycho-social issues, and poorer QoL. Dysfunctional cognitive control at a meta-level may impact someone's ability to rationally identify cognitive changes, increase worry about cognitive changes, and allow such changes to impact their lives more than those with superior metacognitive control. Findings could impact SCD assessment, monitoring, early intervention, and ultimately reducing risk of further decline.
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Sintomas Afetivos/psicologia , Disfunção Cognitiva/psicologia , Autoavaliação Diagnóstica , Metacognição , Neuroticismo , Estresse Psicológico/psicologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Qualidade de Vida/psicologiaRESUMO
Although subjective cognitive impairment (SCI) is increasingly recognized clinically and in research as a risk factor for mild cognitive impairment and dementia (particularly Alzheimer's disease), it is etiologically heterogeneous and potentially treatable. Compared to mild cognitive impairment and Alzheimer's disease, SCI however remains poorly characterized with debate continuing regarding its clinical relevance. The primary aim of this study was to improve the characterization of SCI within the general public by investigating functions sometimes omitted clinically or in research, namely visual attention-related information processing speed (RT) and its intra-individual variability (IIVRT), general cognition, depression, anxiety, memory, quality of life (QOL), and neuroticism. Compared to individuals without SCI, those with SCI were more likely to reveal higher scores of anxiety, depression, and neuroticism and poorer perceived physical, psychological, and environmental QOL. Within-group analysis identified no significant relationships between any of the above variables for the non-SCI group whereas for the SCI group, poorer Cognitive Change Index scores were significantly correlated with slower RT, raised IIVRT, poorer memory, negative affective symptoms, higher neuroticism scores, and poorer QOL. This indicates that reports of perceived memory changes in SCI can also be associated with other characteristics, namely objectively measured detrimental change in other aspects of brain function and behavior. This outcome emphasizes the importance of a multi-function approach to characterizing and understanding SCI. Thus, although the effect of RT and IIVRT is not strong enough to differentiate SCI from non-SCI at group level, slowing and raised IIVRT do appear to characterize some people with SCI.
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Sintomas Afetivos/psicologia , Disfunção Cognitiva , Autoavaliação Diagnóstica , Qualidade de Vida , Autoimagem , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Correlação de Dados , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Transtornos da Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos , Neuroticismo , Técnicas PsicológicasRESUMO
INTRODUCTION: Many institutions evaluate applications for local seed funding by recruiting peer reviewers from their own institutional community. Smaller institutions, however, often face difficulty locating qualified local reviewers who are not in conflict with the proposal. As a larger pool of reviewers may be accessed through a cross-institutional collaborative process, nine Clinical and Translational Science Award (CTSA) hubs formed a consortium in 2016 to facilitate reviewer exchanges. Data were collected to evaluate the feasibility and preliminary efficacy of the consortium. METHODS: The CTSA External Reviewer Exchange Consortium (CEREC) has been supported by a custom-built web-based application that facilitates the process and tracks the efficiency and productivity of the exchange. RESULTS: All nine of the original CEREC members remain actively engaged in the exchange. Between January 2017 and May 2019, CEREC supported the review process for 23 individual calls for proposals. Out of the 412 reviews requested, 368 were received, for a fulfillment ratio of 89.3%. The yield on reviewer invitations has remained consistently high, with approximately one-third of invitations being accepted, and of the reviewers who agreed to provide a review, 88.3% submitted a complete review. Surveys of reviewers and pilot program administrators indicate high satisfaction with the process. CONCLUSIONS: These data indicate that a reviewer exchange consortium is feasible, adds value to participating partners, and is sustainable over time.
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TenA catalyzes the hydrolysis of 4-amino-5-aminomethyl-2-methylpyrimidine and participates in the salvage of base-degraded thiamin. Here, we describe mutagenesis of the active site of TenA guided by structures of the enzyme complexed to a substrate analog and to the product. Catalytic roles for each of the active site residues are identified and a mechanism for the reaction is described.
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Bacillus subtilis/enzimologia , Hidrolases/genética , Tiamina/metabolismo , Sítios de Ligação , Catálise , Hidrolases/química , Hidrolases/isolamento & purificação , Hidrólise , Modelos Moleculares , Estrutura Molecular , Mutagênese Sítio-Dirigida , Relação Estrutura-Atividade , Tiamina/químicaRESUMO
Programmable nuclease-based genome editing technologies, including the clustered, regularly interspaced, short palindromic repeats (CRISPR)/Cas9 system, are becoming an essential component of many applications ranging from agriculture to medicine. However, fundamental limitations currently prevent the widespread, safe, and practical use of genome editors, especially for human disease interventions. These limitations include off-target effects, a lack of control over editing activity, suboptimal DNA repair outcomes, insufficient target conversion, and inadequate delivery performance. This perspective focuses on the potential for biological chemistry to address these limitations such that newly developed genome editing technologies can enable the broadest range of potential future applications. Equally important will be the development of these powerful technologies within a relevant ethical framework that emphasizes safety and responsible innovation.
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Biologia/métodos , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Genoma , Animais , Biologia/ética , Proteínas Associadas a CRISPR/metabolismo , DNA/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades/genética , Endonucleases/metabolismo , Edição de Genes/ética , Técnicas de Transferência de Genes , Humanos , RNA Guia de Cinetoplastídeos/genéticaRESUMO
The authors identified individual randomized controlled trials from previous meta-analyses and additional searches, and then performed meta-analyses on cardiovascular disease outcomes and all-cause mortality. The authors assessed publications from 2012, both before and including the U.S. Preventive Service Task Force review. Their systematic reviews and meta-analyses showed generally moderate- or low-quality evidence for preventive benefits (folic acid for total cardiovascular disease, folic acid and B-vitamins for stroke), no effect (multivitamins, vitamins C, D, ß-carotene, calcium, and selenium), or increased risk (antioxidant mixtures and niacin [with a statin] for all-cause mortality). Conclusive evidence for the benefit of any supplement across all dietary backgrounds (including deficiency and sufficiency) was not demonstrated; therefore, any benefits seen must be balanced against possible risks.
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Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/prevenção & controle , Dieta Saudável/tendências , Suplementos Nutricionais , Oligoelementos/administração & dosagem , Vitaminas/administração & dosagem , Doenças Cardiovasculares/epidemiologia , Dieta Saudável/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Dietary recommendations emphasize increased consumption of fruit, vegetables, and whole grain cereals for prevention of chronic disease. OBJECTIVES: This study assessed the effect of dietary advice and/or food provision on body weight and cardiovascular disease risk factors. METHODS: Healthy overweight men (n = 209) and women (n = 710), mean age 44.7 years, body mass index [BMI] 32.4 kg/m2, were randomized between November 2005 and August 2009 to receive Health Canada's food guide (control, n = 486) or 1 of 3 interventions: dietary advice consistent with both Dietary Approaches to Stop Hypertension (DASH) and dietary portfolio principles (n = 145); weekly food provision reflecting this advice (n = 148); or food delivery plus advice (n = 140). Interventions lasted 6 months with 12-month follow-up. Semiquantitative food frequency questionnaires and fasting blood, anthropometric and blood pressure measurements were obtained at baseline, 6 months, and 18 months. RESULTS: Participant retention at 6 and 18 months was 91% and 81%, respectively, after food provision compared to 67% and 57% when no food was provided (p < 0.0001). Test and control treatments showed small reductions in body weight (-0.8 to -1.2 kg), waist circumference (-1.1 to -1.9 cm), and mean arterial pressure (0.0 to -1.1 mm Hg) at 6 months and Framingham coronary heart disease risk score at 18 months (-0.19 to -0.42%), which were significant overall. Outcomes did not differ among test and control groups. CONCLUSIONS: Provision of foods increased retention but only modestly increased intake of recommended foods. Current dietary recommendations showed small overall benefits in coronary heart disease risk factors. Additional dietary strategies to maximize these benefits are required. (Fruits, Vegetables, and Whole Grains: A Community-based Intervention; NCT00516620).
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Doenças Cardiovasculares/prevenção & controle , Dieta , Sobrepeso/dietoterapia , Redução de Peso , Adulto , Índice de Massa Corporal , Canadá , Feminino , Frutas , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso/complicações , Cooperação do Paciente , Fatores de Risco , Verduras , Grãos IntegraisRESUMO
Mobile technologies, such as tablet devices, open up new possibilities for health-related diagnosis, monitoring, and intervention for older adults and healthcare practitioners. Current evaluations of cognitive integrity typically occur within clinical settings, such as memory clinics, using pen and paper or computer-based tests. In the present study, we investigate the challenges associated with transferring such tests to touch-based, mobile technology platforms from an older adult perspective. Problems may include individual variability in technical familiarity and acceptance; various factors influencing usability; acceptability; response characteristics and thus validity per se of a given test. For the results of mobile technology-based tests of reaction time to be valid and related to disease status rather than extraneous variables, it is imperative the whole test process is investigated in order to determine potential effects before the test is fully developed. Researchers have emphasized the importance of including the 'user' in the evaluation of such devices; thus we performed a focus group-based qualitative assessment of the processes involved in the administration and performance of a tablet-based version of a typical test of attention and information processing speed (a multi-item localization task), to younger and older adults. We report that although the test was regarded positively, indicating that using a tablet for the delivery of such tests is feasible, it is important for developers to consider factors surrounding user expectations, performance feedback, and physical response requirements and to use this information to inform further research into such applications.