Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
1.
J Alzheimers Dis ; 80(3): 1231-1242, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33646150

RESUMO

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.


Assuntos
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/psicologia
2.
J Clin Transl Sci ; 3(6): 325-331, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31827906

RESUMO

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.

3.
Health Res Policy Syst ; 17(1): 25, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30832733

RESUMO

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.


Assuntos
Atitude , Pesquisa Biomédica , Revelação , Disseminação de Informação , Pesquisadores , Sujeitos da Pesquisa , Comunicação , Humanos , Inquéritos e Questionários , Estados Unidos
4.
Yale J Biol Med ; 92(1): 13-20, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30923469

RESUMO

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.


Assuntos
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 Jovem
5.
J Alzheimers Dis ; 67(4): 1367-1378, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30689577

RESUMO

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.


Assuntos
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 Psicológicas
6.
J Am Coll Cardiol ; 71(22): 2570-2584, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29852980

RESUMO

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.


Assuntos
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 Tratamento
7.
ACS Chem Biol ; 13(2): 333-342, 2018 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-28992411

RESUMO

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.


Assuntos
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/genética
8.
J Card Fail ; 23(11): 794-799, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28363805

RESUMO

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.


Assuntos
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 Retrospectivos
9.
J Am Coll Cardiol ; 69(9): 1103-1112, 2017 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-28254171

RESUMO

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).


Assuntos
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 Integrais
10.
Pacing Clin Electrophysiol ; 39(10): 1061-1069, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27566614

RESUMO

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.


Assuntos
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 Questionários
11.
J Alzheimers Dis ; 54(3): 1169-1182, 2016 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-27567875

RESUMO

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.


Assuntos
Cognição/fisiologia , Computadores de Mão/estatística & dados numéricos , Testes de Estado Mental e Demência , Desempenho Psicomotor/fisiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Adulto Jovem
12.
J Card Fail ; 22(11): 908-912, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27150493

RESUMO

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.


Assuntos
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 Jovem
13.
JACC Heart Fail ; 3(12): 965-76, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26671675

RESUMO

OBJECTIVES: This study aimed to create decision aids (DAs) for patients considering a destination therapy left ventricular assist device (DT LVAD). BACKGROUND: Insertion of a DT LVAD is a major decision for patients with end-stage heart failure. Patients facing decisions with complex trade-offs may benefit from high-quality decision support resources. METHODS: In accordance with the International Patient Decision Aid Standards guidelines and based on a needs assessment with stakeholders, we developed drafts of paper and video DAs. With input from patients, caregivers, and clinicians through alpha testing, we iteratively modified the DAs to ensure acceptability. RESULTS: We conducted semistructured interviews with 24 patients, 20 caregivers, and 24 clinicians to assess readability, bias, and usability of the DAs. Stakeholder feedback allowed us to integrate aspects critical to decision making around highly invasive therapies for life-threatening diseases, including addressing emotion and fear of death, using gain frames for all options that focus on living, highlighting palliative and hospice care, integrating the caregiver role, and using a range of balanced testimonials. After 19 iterative versions of the paper DA and 4 versions of the video DA, final materials were made available for wider use. CONCLUSIONS: We developed the first International Patient Decision Aid Standards-level DAs for DT LVAD. Given the extreme nature of this medical decision, we augmented traditional DA characteristics with nontraditional DA features to address a spectrum of cognitive, automatic, and emotional aspects of end-of-life decision making. Not only are the DAs important tools for those confronting end-stage heart failure, but the lessons learned will likely inform decision support for other invasive therapies.


Assuntos
Tomada de Decisões , Técnicas de Apoio para a Decisão , Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Qualidade de Vida , Adulto , Idoso , Feminino , Insuficiência Cardíaca/psicologia , Humanos , Masculino , Pessoa de Meia-Idade
14.
J Alzheimers Dis ; 48 Suppl 1: S25-31, 2015 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-26445273

RESUMO

Extensive research on the concept of mild cognitive impairment (MCI) as a potential prodromal stage of dementia has highlighted the likelihood that abnormalities in information processing occur at even earlier stages in the disease process with research increasingly focused on the relatively new concept of subjective cognitive impairment (SCI). An individual with SCI will experience cognitive impairment solely on a subjective level, which is in contrast to an individual with MCI who will also experience cognitive impairment at an objective level. SCI is believed to be a risk factor for development of MCI. This qualitative service evaluation aimed to determine how much is known about SCI and how it is currently managed in specialist clinical practice in the UK. An email-based questionnaire containing a vignette of an individual presenting with SCI was distributed to 112 memory clinics requesting information on their most likely approach to such an individual. The 21% response rate evinces potential time pressure within clinical services that may preclude research participation and/or a lack of issue salience at present. However, the data from those who responded provide an important insight into 'where we are now' in relation to this issue. Analysis revealed main themes associated with SCI, namely the factors that influence what action is taken when an individual presents and what further investigations are performed, the multiplicity of potential outcomes experienced, and the barriers clinicians may face. The findings highlight the need for a coherent and consistent framework in relation to the management of SCI.


Assuntos
Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Inquéritos e Questionários , Reino Unido/epidemiologia
16.
mBio ; 6(1): e02272-14, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25691592

RESUMO

UNLABELLED: Staphylococcus aureus is a Gram-positive, commensal bacterium known to asymptomatically colonize the human skin, nares, and gastrointestinal tract. Colonized individuals are at increased risk for developing S. aureus infections, which range from mild skin and soft tissue infections to more severe diseases, such as endocarditis, bacteremia, sepsis, and osteomyelitis. Different virulence factors are required for S. aureus to infect different body sites. In this study, virulence gene expression was analyzed in two S. aureus isolates during nasal colonization, bacteremia and in the heart during sepsis. These models were chosen to represent the stepwise progression of S. aureus from an asymptomatic colonizer to an invasive pathogen. Expression of 23 putative S. aureus virulence determinants, representing protein and carbohydrate adhesins, secreted toxins, and proteins involved in metal cation acquisition and immune evasion were analyzed. Consistent upregulation of sdrC, fnbA, fhuD, sstD, and hla was observed in the shift between colonization and invasive pathogen, suggesting a prominent role for these genes in staphylococcal pathogenesis. Finally, gene expression data were correlated to the roles of the genes in pathogenesis by using knockout mutants in the animal models. These results provide insights into how S. aureus modifies virulence gene expression between commensal and invasive pathogens. IMPORTANCE: Many bacteria, such as Staphylococcus aureus, asymptomatically colonize human skin and nasal passages but can also cause invasive diseases, such as bacteremia, pneumonia, sepsis, and osteomyelitis. The goal of this study was to analyze differences in the expression of selected S. aureus genes during a commensal lifestyle and as an invasive pathogen to gain insight into the commensal-to-pathogen transition and how a bacterial pathogen adapts to different environments within a host (e.g., from nasal colonization to invasive pathogen). The gene expression data were also used to select genes for which to construct knockout mutants to assess the role of several proteins in nasal colonization and lethal bacteremia. These results not only provide insight into the factors involved in S. aureus disease pathogenesis but also provide potential therapeutic targets.


Assuntos
Portador Sadio/microbiologia , Regulação Bacteriana da Expressão Gênica , Osteomielite/microbiologia , Sepse/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Fatores de Virulência/biossíntese , Animais , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Técnicas de Inativação de Genes , Camundongos Endogâmicos BALB C , Sigmodontinae , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade , Virulência , Fatores de Virulência/genética
17.
J Clin Microbiol ; 53(1): 227-36, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25392350

RESUMO

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.


Assuntos
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 Jovem
18.
PLoS One ; 9(8): e104524, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25101850

RESUMO

Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.


Assuntos
Proteínas de Bactérias , Deleção de Genes , Proteínas de Membrana Transportadoras , Peste , Pneumonia Bacteriana , Yersinia pestis , Aerossóis , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Modelos Animais de Doenças , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Peste/genética , Peste/metabolismo , Peste/patologia , Pneumonia Bacteriana/genética , Pneumonia Bacteriana/metabolismo , Pneumonia Bacteriana/patologia , Yersinia pestis/genética , Yersinia pestis/metabolismo , Yersinia pestis/patogenicidade
19.
Microb Pathog ; 57: 41-51, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23178382

RESUMO

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.


Assuntos
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 , Virulência
20.
Body Image ; 9(3): 381-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22609033

RESUMO

Latina women are vulnerable to poor body image, eating disorders, and obesity, particularly during the college years. This study sought to identify common cultural antecedents of these concerns in order to inform the development of prevention programs for this population. Six groups of university students who identified as Latina (N=27) discussed cultural aspects of body image, eating disorders, and obesity. Thematic analysis identified four main themes: (a) cultural disparities in body-ideal, including the influence of the media and acculturation issues; (b) messages about body shape and weight received by family, peers, and society; (c) difficulties making healthy eating and physical activity choices as a function of college life; and (d) the influence of peers and potential male partners on body satisfaction and body-ideals. These results have implications for the development of programs targeting body dissatisfaction and risk for eating disorders and obesity in Latina college women.


Assuntos
Imagem Corporal , Transtornos da Alimentação e da Ingestão de Alimentos/prevenção & controle , Hispânico ou Latino/psicologia , Meios de Comunicação de Massa , Obesidade/prevenção & controle , Aculturação , Adolescente , Transtornos da Alimentação e da Ingestão de Alimentos/etnologia , Feminino , Grupos Focais , Humanos , Narração , Obesidade/etnologia , Fatores de Risco , Valores Sociais , Estudantes/psicologia , Estados Unidos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA