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BACKGROUND: Hearing loss is associated with increased cognitive decline and incident dementia in older adults. We aimed to investigate whether a hearing intervention could reduce cognitive decline in cognitively healthy older adults with hearing loss. METHODS: The ACHIEVE study is a multicentre, parallel-group, unmasked, randomised controlled trial of adults aged 70-84 years with untreated hearing loss and without substantial cognitive impairment that took place at four community study sites across the USA. Participants were recruited from two study populations at each site: (1) older adults participating in a long-standing observational study of cardiovascular health (Atherosclerosis Risk in Communities [ARIC] study), and (2) healthy de novo community volunteers. Participants were randomly assigned (1:1) to a hearing intervention (audiological counselling and provision of hearing aids) or a control intervention of health education (individual sessions with a health educator covering topics on chronic disease prevention) and followed up every 6 months. The primary endpoint was 3-year change in a global cognition standardised factor score from a comprehensive neurocognitive battery. Analysis was by intention to treat. This trial was registered at ClinicalTrials.gov, NCT03243422. FINDINGS: From Nov 9, 2017, to Oct 25, 2019, we screened 3004 participants for eligibility and randomly assigned 977 (32·5%; 238 [24%] from ARIC and 739 [76%] de novo). We randomly assigned 490 (50%) to the hearing intervention and 487 (50%) to the health education control. The cohort had a mean age of 76·8 years (SD 4·0), 523 (54%) were female, 454 (46%) were male, and most were White (n=858 [88%]). Participants from ARIC were older, had more risk factors for cognitive decline, and had lower baseline cognitive scores than those in the de novo cohort. In the primary analysis combining the ARIC and de novo cohorts, 3-year cognitive change (in SD units) was not significantly different between the hearing intervention and health education control groups (-0·200 [95% CI -0·256 to -0·144] in the hearing intervention group and -0·202 [-0·258 to -0·145] in the control group; difference 0·002 [-0·077 to 0·081]; p=0·96). However, a prespecified sensitivity analysis showed a significant difference in the effect of the hearing intervention on 3-year cognitive change between the ARIC and de novo cohorts (pinteraction=0·010). Other prespecified sensitivity analyses that varied analytical parameters used in the total cohort did not change the observed results. No significant adverse events attributed to the study were reported with either the hearing intervention or health education control. INTERPRETATION: The hearing intervention did not reduce 3-year cognitive decline in the primary analysis of the total cohort. However, a prespecified sensitivity analysis showed that the effect differed between the two study populations that comprised the cohort. These findings suggest that a hearing intervention might reduce cognitive change over 3 years in populations of older adults at increased risk for cognitive decline but not in populations at decreased risk for cognitive decline. FUNDING: US National Institutes of Health.
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Aterosclerose , Disfunção Cognitiva , Perda Auditiva , Humanos , Masculino , Feminino , Idoso , Disfunção Cognitiva/prevenção & controle , Cognição , Perda Auditiva/prevenção & controle , Audição , Educação em SaúdeRESUMO
Objectives. To produce a database of private insurance hearing aid mandates in the United States and quantify the share of privately insured individuals covered by a mandate. Methods. We used health-related policy surveillance methods to create a database of private insurance hearing aid mandates through January 2023. We coded salient features of mandates and combined policy data with American Community Survey and Medicare Expenditure Panel Survey-Insurance Component data to estimate the share of privately insured US residents covered by a mandate from 2008 to 2022. Results. A total of 26 states and 1 territory had private insurance hearing aid mandates. We found variability for mandate exceptions, maximum age eligibility, allowable frequency of benefit use, and coverage amounts. Between 2008 and 2022 the proportion of privately insured youths (aged ≤ 18 years) living where there was a private insurance hearing aid mandate increased from 3.4% to 18.7% and the proportion of privately insured adults (19-64 years) increased from 0.3% to 4.6%. Conclusions. Hearing aid mandates cover a small share of US residents. Mandate exceptions in several states limit coverage, particularly for adults. Public Health Implications. A federal mandate would improve hearing aid access. States can also improve access by adopting exception-free mandates with limited utilization management and no age restrictions. (Am J Public Health. 2024;114(4):407-414. https://doi.org/10.2105/AJPH.2023.307551).
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Auxiliares de Audição , Cobertura do Seguro , Adulto , Adolescente , Humanos , Estados Unidos , Idoso , Epidemiologia Legal , Medicare , Política de Saúde , Seguro SaúdeRESUMO
OBJECTIVES: Hearing loss is a highly prevalent condition; however, it is widely under-treated, and Black Americans have been found to have significantly lower rates of hearing aid utilization than other ethnic/racial groups. In this exploratory study, we aimed to identify hearing health beliefs among Black adults, guided by the Health Belief Model, with social determinants of health, and examine individual differences in these perspectives. DESIGN: The Hearing Beliefs Questionnaire (HBQ) was administered online to measure constructs of the Health Belief Model among 200 Black adults aged 18 to 75 (M = 39.14, SD = 14.24). Approximately 13% reported hearing difficulty. In addition, 11 social determinants of health questions were included. Participants were recruited from a university otolaryngology clinic and local Black congregations, meeting inclusion criteria of being 18 or older and Black/African American. Mean scores and SDs for HBQ subscales were calculated. Analysis included analysis of variance and t tests to explore relationships with demographic variables and social determinants of health. Multiple regression analyses predicted HBQ subscale scores from sociodemographic variables. RESULTS: Mean HBQ subscale scores ranged from 3.88 (SD = 2.28) for Perceived Barriers to 6.76 (SD = 1.93) for Perceived Benefits. Positive correlations were observed between Perceived Severity, Perceived Benefits, and Perceived Self-Efficacy scores and participant educational attainment. Lower economic stability was correlated with poorer scores in Perceived Self-Efficacy, Perceived Severity, and Perceived Benefits. Black adults' willingness to purchase a hearing aid was heavily influenced by their Perceived Benefit, Perceived Severity, and Perceived Self-Efficacy scores, with lower scores correlating with unwillingness to purchase devices. Higher frequency of racism/discrimination and financial hardship correlated with increased Perceived Barriers scores for accessing hearing healthcare. In addition, hearing health beliefs between participants with self-reported hearing difficulty and those without trouble only exhibited differences in the Perceived Susceptibility subscale, with those experiencing hearing difficulty having higher scores in this subscale; no other distinctions were identified. CONCLUSIONS: The Health Belief Model, used with social determinants of health, revealed associations, and variations, in the hearing health beliefs held by Black adults. The present investigation reveals heterogeneity within this group and pinpoints individuals at higher risk for untreated hearing loss, stemming from their negative perceptions about hearing healthcare. These beliefs are influenced by demographics and social determinants of health, underscoring areas ripe for intervention.
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INTRODUCTION: Many neurocognitive evaluations involve auditory stimuli, yet there are no standard testing guidelines for individuals with hearing loss. The ensuring speech understanding (ESU) test was developed to confirm speech understanding and determine whether hearing accommodations are necessary for neurocognitive testing. METHODS: Hearing was assessed using audiometry. The probability of ESU test failure by hearing status was estimated in 2679 participants (mean age: 81.4 ± 4.6 years) using multivariate logistic regression. RESULTS: Only 2.2% (N = 58) of participants failed the ESU test. The probability of failure increased with hearing loss severity; similar results were observed for those with and without mild cognitive impairment or dementia. DISCUSSION: The ESU test is appropriate for individuals who have variable degrees of hearing loss and cognitive function. This test can be used prior to neurocognitive testing to help reduce the risk of hearing loss and compromised auditory access to speech stimuli causing poorer performance on neurocognitive evaluation.
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Disfunção Cognitiva , Perda Auditiva , Humanos , Idoso , Idoso de 80 Anos ou mais , Fala , Perda Auditiva/diagnóstico , Perda Auditiva/complicações , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Testes Auditivos/efeitos adversos , Testes Auditivos/métodosRESUMO
The purpose of this study was to estimate the prevalence of occupational noise exposure and risk factors of occupational noise-induced hearing loss (NIHL) in Hispanic/Latino adults included in the baseline wave of the Hispanic Community Health Study/Study of Latinos collected from 2008 to 2011. Sequential multiple linear regression modeled the relationship between occupational NIHL (defined as a 3-, 4-, 6-kHz pure-tone average [PTA]) and occupation type, self-reported noise exposure, cardiovascular disease (CVD) risk score, and hearing protective device (HPD) use. The final model controlled for sex, age, and recreational noise exposure. Among 12,851 included participants, approximately 40% (n = 5036) reported occupational noise exposure "Sometimes" (up to 50% of the time) or "Frequently" (75-100% of the time). In the final fitted model, longest-held occupation and CVD risk were associated with poorer hearing. Specifically, those in non-skilled, service, skilled, and military/police/other job categories had between 2.07- and 3.29-dB worse PTA than professional/office workers. Additionally, a shift in the CVD risk score category from low to medium was associated with a 2.25- and 8.20-dB worse PTA for medium and high CVD risk, respectively. Age and sex were also significantly associated with poorer hearing, such that men presented with 6.08 dB worse PTA than women, and for every one-year increase in age, PTA increased by 0.62 dB (ps < .001). No interactions were seen between noise*sometimes or frequent exposure to other ototoxic agents and PTA (ps = .33 & .92, respectively). The prevalence of occupational noise exposure was high in this cross-sectional investigation of adults from Hispanic/Latino backgrounds. Findings contribute to the extant literature by demonstrating that risk factors for occupational NIHL in adults from varying Hispanic/Latino backgrounds are consistent with those of other previously studied groups.
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Doenças Cardiovasculares , Perda Auditiva Provocada por Ruído , Ruído Ocupacional , Doenças Profissionais , Exposição Ocupacional , Masculino , Adulto , Humanos , Feminino , Perda Auditiva Provocada por Ruído/epidemiologia , Perda Auditiva Provocada por Ruído/etiologia , Saúde Pública , Estudos Transversais , Ruído Ocupacional/efeitos adversos , Fatores de Risco , Exposição Ocupacional/efeitos adversos , Hispânico ou Latino , Doenças Cardiovasculares/complicações , Doenças Profissionais/epidemiologiaRESUMO
OBJECTIVES: To better understand the hearing health learning needs of Hispanic/Latino adults by assessing hearing healthcare (HHC) knowledge, attitudes, and behaviors to inform the development of a culturally and linguistically appropriate self-management program. Through a series of focus groups with members of the target audience, this study explored knowledge about hearing loss and interventions, cultural facilitators and barriers to HHC utilization, and preferences for hearing health education and information delivery. Opinions were also received on patient education materials designed to increase self-efficacy for managing hearing loss in daily life. DESIGN: This work was guided by a practical framework of culturally competent interventions for addressing disparities in health and healthcare, centered on structural, clinical, and organizational barriers to care. A hybrid individualistic social psychology and social constructionist approach was used to build programmatic theory related to the primary research objective. Focus group goals were to generate a combination of personal opinions and collective experiences from participants with an a priori plan to analyze data using combined content analysis/grounded theory methods. Purposive sampling was used to select 31 participants who were Spanish-speaking, identified as Hispanic/Latino, and who had normal hearing or self-reported hearing difficulties. Thirteen focus groups were conducted using Microsoft Teams, and each group was audio and video recorded for later off-line transcription, translation, and analysis. A constant comparison approach was used to systematically organize focus group data into a structured format for interpretation. Transcripts were coded independently by two investigators, and emergent themes were derived and interpreted from the coded data. RESULTS: Major and minor themes tied to the framework for culturally competent interventions included those related to sociocultural barriers to care. Structural barriers, including inconsistent access to quality care, lack of culturally and linguistically appropriate patient education materials, appointment wait times and intake processes, and referrals to specialty care, were most frequently experienced by participants. Clinical barriers most frequently cited were a lack of culturally and linguistically congruent healthcare providers and lack of language access during healthcare visits. Other major themes included hearing loss lived experiences, family and familism, and hearing-related patient education needs and preferences. CONCLUSIONS: Focus group results were integrated into a Spanish-language hearing loss self-management program that is currently being evaluated in a randomized controlled trial. The themes uncovered provided insight regarding the knowledge, attitudes, and beliefs about hearing loss and HHC, including hearing-related learning needs, of Hispanic/Latino adults in this sample.
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Surdez , Perda Auditiva , Humanos , Grupos Focais , Atenção à Saúde , Hispânico ou Latino , AudiçãoRESUMO
OBJECTIVE: Since the global outbreak of the novel coronavirus disease 2019 (COVID-19), there have been increasing reports of children developing a croup-like cough associated with concurrent COVID-19 infection. Currently, there is not much information available regarding newborn infants and COVID-19 infection and the incidence of vertical transmission is thought to be rare. This novel case report depicts a term newborn infected at the time of birth with COVID-19 and includes details about the course of their complicated hospitalization. STUDY DESIGN: A term infant, found to be infected at birth with COVID-19, developed respiratory distress resulting in transfer to our neonatal intensive care unit. Due to the increasing respiratory support requirements, endotracheal intubation was required on day of life (DOL) 7. Later, when the infant was extubated, on DOL 21, a croup-like cough developed. RESULTS: Despite respiratory treatment with albuterol, budesonide, racemic epinephrine, lidocaine, dornase alfa, and a 10-day course of dexamethasone, the cough persisted. A prolonged hospitalization was required and eventually the infant was discharged home on 0.4 L/minute of oxygen via nasal cannula on DOL 95. CONCLUSION: As the COVID-19 virus mutates over time, there are some seemingly different presentations in both the pediatric and adult populations. The hypervigilance and sharing of new findings among providers are paramount in the treatment of infants with COVID-19 disease. KEY POINTS: · Term infant with COVID-19 developed a croup-like cough.. · Usual respiratory treatment not effective with croup-like cough and COVID-19.. · COVID-19 present at birth later requiring intubation..
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Speech perception testing, defined as providing standardized speech stimuli and requiring a listener to provide a behavioral and scored response, has been an integral part of the audiologic test battery since the beginning of the audiology profession. Over the past several decades, limitations in the diagnostic and prognostic validity of standard speech perception testing as routinely administered in the clinic have been noted, and the promotion of speech-in-noise testing has been highlighted. This review will summarize emerging and innovative approaches to speech-in-noise testing with a focus on five applications: (1) pediatric considerations promoting the measurement of sensory and cognitive components separately; (2) appropriately serving underrepresented populations with special attention to racial, ethnic, and linguistic minorities, as well as considering biological sex and/or gender differences as variables of interest; (3) binaural fitness for duty assessments of functional hearing for occupational settings that demand the ability to detect, recognize, and localize sounds; (4) utilization of speech-in-noise tests in pharmacotherapeutic clinical trials with considerations to the drug mechanistic action, the patient populations, and the study design; and (5) online and mobile applications of hearing assessment that increase accessibility and the direct-to-consumer market.
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Percepção da Fala , Humanos , Criança , Percepção da Fala/fisiologia , Fala , Ruído , Audição/fisiologia , Testes AuditivosRESUMO
OBJECTIVE: Studies investigating hearing interventions under-utilise and under-report treatment fidelity planning, implementation, and assessment. This represents a critical gap in the field that has the potential to impede advancements in the successful dissemination and implementation of interventions. Thus, our objective was to describe treatment fidelity planning and implementation for hearing intervention in the multi-site Ageing and Cognitive Health Evaluation in Elders (ACHIEVE) randomised controlled trial. DESIGN: Our treatment fidelity plan was based on a framework defined by the National Institutes of Health Behaviour Change Consortium (NIH BCC), and included strategies to enhance study design, provider training, and treatment delivery, receipt, and enactment. STUDY SAMPLE: To assess the fidelity of the ACHIEVE hearing intervention, we distributed a checklist containing criteria from each NIH BCC core treatment fidelity category to nine raters. RESULTS: The ACHIEVE hearing intervention fidelity plan satisfied 96% of NIH BCC criteria. Our assessment suggested a need for including clear, objective definitions of provider characteristics and non-treatment aspects of intervention delivery in future fidelity plans. CONCLUSIONS: The ACHIEVE hearing intervention fidelity plan can serve as a framework for the application of NIH BCC fidelity strategies for future studies and enhance the ability of researchers to reliably implement evidence-based interventions.
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Audiologia , Projetos de Pesquisa , Idoso , Envelhecimento , Cognição , HumanosRESUMO
OBJECTIVES: We sought to determine what factors, including acculturation (language and social contact preferences), were associated with self-perceived hearing handicap among adults from Hispanic/Latino background. We utilized the Aday-Andersen behavioral model of health services utilization to frame our hypotheses that predisposing characteristics (age, sex, education, city of residence, Hispanic/Latino background, and acculturation), enabling resources (annual income and current health insurance coverage), and need (measured hearing loss and self-reported hearing loss) would be related to clinically-significant self-perceived hearing handicap as measured by the Hearing Handicap Inventory - Screening (HHI-S) version. DESIGN: We analyzed baseline data collected from 2008 to 2011 as part of the multisite Hispanic Community Health Study/Study of Latinos. Data were from 6585 adults with hearing loss (defined by a worse-ear 500, 1000, 2000, and 4000 Hz pure-tone average [PTA] of ≥25 dB HL and/or a 4000, 6000, and 8000 Hz high-frequency PTA of ≥25 dB HL) aged 18 to 74 years from various Hispanic/Latino backgrounds. We conducted a series of multivariable logistic regression models examining the roles of independent variables of interest representing predisposing, enabling, and need indicators on the occurrence of clinically-significant self-perceived hearing handicap (e.g., HHI-S score > 8). RESULTS: Among included participants, 953 (14.5%) had an HHI-S score >8. The final model revealed significant associations between predisposing characteristics, enabling resources, need, and HHI-S outcome. Predisposing characteristics and need factors were associated with higher odds of reporting self-perceived hearing handicap (HHI-S score >8) including acculturation as measured by the Short Acculturation Scale for Hispanics (odds ratio [OR] = 1.28, 95% confidence interval [CI]: 1.09-1.50), female sex (OR = 1.72, 95% CI: 1.27-2.33), and poorer worse ear 500, 1000, 2000, and 4000 Hz PTA (OR = 1.02, 95% CI: 1.01-1.03); suggesting that a 5-decibel increase in a person's PTA was consistent with 10% higher odds of a HHI-S score of >8. Greater enabling resources were associated with lower odds of reporting clinically-significant self-perceived hearing handicap: compared with individuals with income <$10,000/year, the multivariable-adjusted OR among individuals with income $40,000 to $7500/year was 0.55 (95% CI: 0.33-0.89) and among individuals with income >$75,000/year was 0.28 (95% CI: 0.13-0.59]; p-trend < 0.0001). CONCLUSIONS: Our findings suggest there are associations between predisposing, enabling and need variables consistent with the Aday-Andersen model and self-perceived hearing handicap among adults from Hispanic/Latino background. The influence of language and culture on perceived hearing loss and associated handicap is complex, and deserves more attention in future studies. Our findings warrant further investigation into understanding the role of language and language access in hearing health care utilization and outcomes, as the current body of literature is small and shows mixed outcomes.
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Perda Auditiva , Hispânico ou Latino , Adulto , Feminino , Audição , Humanos , Razão de Chances , AutorrelatoRESUMO
OBJECTIVES: This work describes the development of a manualized best-practice hearing intervention for older adults participating in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) randomized controlled clinical trial. Manualization of interventions for clinical trials is critical for assuring intervention fidelity and quality, especially in large multisite studies. The multisite ACHIEVE randomized controlled trial is designed to assess the efficacy of a hearing intervention on rates of cognitive decline in older adults. We describe the development of the manualized hearing intervention through an iterative process that included addressing implementation questions through the completion of a feasibility study (ACHIEVE-Feasibility). DESIGN: Following published recommendations for manualized intervention development, an iterative process was used to define the ACHIEVE-hearing intervention elements and create an initial manual. The intervention was then delivered within the ACHIEVE-Feasibility study using one-group pre-post design appropriate for assessing questions related to implementation. Participants were recruited from the Tampa, Florida area between May 2015 and April 2016. Inclusion criteria were cognitively healthy adults aged 70 to 89 with symmetrical mild-to-moderately severe sensorineural hearing loss. The ACHIEVE-Feasibility study sought to assess the implementation of the manualized hearing intervention by: (1) confirming improvement in expected outcomes were achieved including aided speech-in-noise performance and perception of disease-specific self-report measures; (2) determining whether the participants would comply with the intervention including session attendance and use of hearing aids; and (3) determining whether the intervention sessions could be delivered within a reasonable timeframe. RESULTS: The initial manualized intervention that incorporated the identified best-practice elements was evaluated for feasibility among 21 eligible participants and 9 communication partners. Post-intervention expected outcomes were obtained with speech-in-noise performance results demonstrating a significant improvement under the aided condition and self-reported measures showing a significant reduction in self-perceived hearing handicap. Compliance was excellent, with 20 of the 21 participants (95.2%) completing all intervention sessions and 19 (90.4%) returning for the 6-month post-intervention visit. Furthermore, self-reported hearing aid compliance was >8 hr/day, and the average daily hearing aid use from datalogging was 7.8 hr. Study completion was delivered in a reasonable timeframe with visits ranging from 27 to 85 min per visit. Through an iterative process, the intervention elements were refined, and the accompanying manual was revised based on the ACHIEVE-Feasibility study activities, results, and clinician and participant informal feedback. CONCLUSION: The processes for the development of a manualized intervention described here provide guidance for future researchers who aim to examine the efficacy of approaches for the treatment of hearing loss in a clinical trial. The manualized ACHIEVE-Hearing Intervention provides a patient-centered, yet standardized, step-by-step process for comprehensive audiological assessment, goal setting, and treatment through the use of hearing aids, other hearing assistive technologies, counseling, and education aimed at supporting self-management of hearing loss. The ACHIEVE-Hearing Intervention is feasible in terms of implementation with respect to verified expected outcomes, compliance, and reasonable timeframe delivery. Our processes assure intervention fidelity and quality for use in the ACHIEVE randomized controlled trial (ClinicalTrials.gov Identifier: NCT03243422).
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Auxiliares de Audição , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Cognição , Estudos de Viabilidade , Audição , HumanosRESUMO
OBJECTIVE: Our objective was to develop and assess a questionnaire measuring the constructs of the theory of planned behaviour (TPB) regarding older adults' behaviours towards seeking a hearing test. DESIGN: Older adults who failed a hearing screening completed a newly developed Theory of Planned Behavior-Hearing Help Seeking (TPB-HHS) questionnaire. A principal components analysis (PCA) examined the factor structure of the questionnaire, and a reliability analysis determined the internal consistency of the factors. An examination of six-month follow-up data determined whether the questionnaire differentiated between individuals who did and did not seek out a hearing test by comparing their TPB-HHS scores. STUDY SAMPLE: Participants were 407 adults aged 50 to 89 recruited at community hearing screenings. RESULTS: PCA and reliability analyses resulted in a 4-factor, 18 item questionnaire. Three of four factors demonstrated acceptable internal consistency. The TPB-HHS explained 60.18% of the variance and factors were interpreted to be measuring the constructs of Intentions, Perceived Behavioral Control, Attitudes, and Subjective Norms. Individuals who sought a hearing test scored significantly higher on the Intentions, Perceived Behavioral Control, and Attitudes scales than those who did not. CONCLUSIONS: The TPB-HHS provides insight into underlying psychological mechanisms that drive behaviours related to hearing help-seeking in older adults.
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Comportamentos Relacionados com a Saúde , Perda Auditiva/psicologia , Testes Auditivos/psicologia , Inquéritos e Questionários , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Rotavirus is a leading cause of death due to diarrhea among young children across the globe. Despite the limited coding capacity that is characteristic of RNA viruses, rotavirus dedicates substantial resources to avoiding the host innate immune response. Among these strategies is use of the interferon antagonist protein NSP1, which targets cellular proteins required for interferon production to be degraded by the proteasome. Although numerous cellular targets have been described, there remain many questions about the mechanism of NSP1 activity and its role in promoting replication in specific host species.
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Interações Hospedeiro-Patógeno , Interferons/antagonistas & inibidores , Interferons/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Infecções por Rotavirus/virologia , Rotavirus/fisiologia , Proteínas não Estruturais Virais/fisiologia , Animais , Especificidade de Hospedeiro , Humanos , Imunidade Inata , Interferons/biossíntese , Interferons/imunologia , Proteólise , Rotavirus/metabolismo , Rotavirus/patogenicidade , Infecções por Rotavirus/imunologia , Transdução de SinaisRESUMO
UNLABELLED: The rotavirus nonstructural protein NSP1 acts as an antagonist of the host antiviral response by inducing degradation of key proteins required to activate interferon (IFN) production. Protein degradation induced by NSP1 is dependent on the proteasome, and the presence of a RING domain near the N terminus has led to the hypothesis that NSP1 is an E3 ubiquitin ligase. To examine this hypothesis, pulldown assays were performed, followed by mass spectrometry to identify components of the host ubiquitination machinery that associate with NSP1. Multiple components of cullin RING ligases (CRLs), which are essential multisubunit ubiquitination complexes, were identified in association with NSP1. The mass spectrometry was validated in both transfected and infected cells to show that the NSP1 proteins from different strains of rotavirus associated with key components of CRL complexes, most notably the cullin scaffolding proteins Cul3 and Cul1. In vitro binding assays using purified proteins confirmed that NSP1 specifically interacted with Cul3 and that the N-terminal region of Cul3 was responsible for binding to NSP1. To test if NSP1 used CRL3 to induce degradation of the target protein IRF3 or ß-TrCP, Cul3 levels were knocked down using a small interfering RNA (siRNA) approach. Unexpectedly, loss of Cul3 did not rescue IRF3 or ß-TrCP from degradation in infected cells. The results indicate that, rather than actively using CRL complexes to induce degradation of target proteins required for IFN production, NSP1 may use cullin-containing complexes to prevent another cellular activity. IMPORTANCE: The ubiquitin-proteasome pathway plays an important regulatory role in numerous cellular functions, and many viruses have evolved mechanisms to exploit or manipulate this pathway to enhance replication and spread. Rotavirus, a major cause of severe gastroenteritis in young children that causes approximately 420,000 deaths worldwide each year, utilizes the ubiquitin-proteasome system to subvert the host innate immune response by inducing the degradation of key components required for the production of interferon (IFN). Here, we show that NSP1 proteins from different rotavirus strains associate with the scaffolding proteins Cul1 and Cul3 of CRL ubiquitin ligase complexes. Nonetheless, knockdown of Cul1 and Cul3 suggests that NSP1 induces the degradation of some target proteins independently of its association with CRL complexes, stressing a need to further investigate the mechanistic details of how NSP1 subverts the host IFN response.
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Proteínas Culina/metabolismo , Interações Hospedeiro-Patógeno , Rotavirus/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas não Estruturais Virais/metabolismo , Proteínas Culina/genética , Citoplasma , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Imunidade Inata , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Espectrometria de Massas , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica , Proteólise , RNA Interferente Pequeno , Rotavirus/genética , Ubiquitina-Proteína Ligases/química , Ubiquitinação , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/imunologia , Proteínas não Estruturais Virais/isolamento & purificaçãoRESUMO
BACKGROUND: Studies have suggested an inverse association between coffee consumption and risk of renal cell carcinoma (RCC); however, data regarding decaffeinated coffee are limited. METHODS: We conducted a case-control study of 669 incident RCC cases and 1,001 frequency-matched controls. Participants completed identical risk factor questionnaires that solicited information about usual coffee consumption habits. The study participants were categorized as non-coffee, caffeinated coffee, decaffeinated coffee, or both caffeinated and decaffeinated coffee drinkers. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression, adjusting for multiple risk factors for RCC. RESULTS: Compared with no coffee consumption, we found an inverse association between caffeinated coffee consumption and RCC risk (OR 0.74; 95% CI 0.57-0.99), whereas we observed a trend toward increased risk of RCC for consumption of decaffeinated coffee (OR 1.47; 95% CI 0.98-2.19). Decaffeinated coffee consumption was associated also with increased risk of the clear cell RCC (ccRCC) subtype, particularly the aggressive form of ccRCC (OR 1.80; 95% CI 1.01-3.22). CONCLUSIONS: Consumption of caffeinated coffee is associated with reduced risk of RCC, while decaffeinated coffee consumption is associated with an increase in risk of aggressive ccRCC. Further inquiry is warranted in large prospective studies and should include assessment of dose-response associations.
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Cafeína/administração & dosagem , Carcinoma de Células Renais/epidemiologia , Café , Neoplasias Renais/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Café/efeitos adversos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
A growing body of research has shown people who hold anomalistic (e.g., paranormal) beliefs may differ from nonbelievers in their propensity to make probabilistic reasoning errors. The current study explored the relationship between these beliefs and performance through the development of a new measure of anomalistic belief, called the Anomalistic Belief Scale (ABS). One key feature of the ABS is that it includes a balance of both experiential and theoretical belief items. Another aim of the study was to use the ABS to investigate the relationship between belief and probabilistic reasoning errors on conjunction fallacy tasks. As expected, results showed there was a relationship between anomalistic belief and propensity to commit the conjunction fallacy. Importantly, regression analyses on the factors that make up the ABS showed that the relationship between anomalistic belief and probabilistic reasoning occurred only for beliefs about having experienced anomalistic phenomena, and not for theoretical anomalistic beliefs.
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Testes Neuropsicológicos , Parapsicologia , Psicometria/instrumentação , Pensamento/fisiologia , Adulto , HumanosRESUMO
Previous studies have shown that punishing people through a large penalty for volunteering incorrect information typically leads them to withhold more information (metacognitive response bias), but it does not appear to influence their ability to distinguish between their own correct and incorrect answers (metacognitive accuracy discrimination). The goal of the current study was to demonstrate that punishing people for volunteering incorrect information-versus rewarding volunteering correct information-produces more effective metacognitive accuracy discrimination. All participants completed three different general-knowledge tests: a reward test (high points for correct volunteered answers), a baseline test (equal points/penalties for volunteered correct/incorrect answers) and a punishment test (high penalty for incorrect volunteered answers). Participants were significantly better at distinguishing between their own correct and incorrect answers on the punishment than reward test, which has implications for situations requiring effective accuracy monitoring.
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Julgamento , Punição , Recompensa , Humanos , Modelos PsicológicosRESUMO
OBJECTIVE: To determine long-term surgical outcomes of salvage autologous fascial sling placement after a failed synthetic midurethral sling. METHODS: Women who had undergone autologous fascial sling placement without concomitant pelvic surgery for a failed synthetic midurethral sling utilizing mesh with a minimum follow up of 36 months were identified. Charts were reviewed, and patients were contacted by telephone. Success was determined by the Patient Global Impression of Improvement. Secondary measures included the Incontinence Severity Index questionnaire, patient recommendation of the autologous fascial sling and need for further incontinence surgery. RESULTS: A total of 35 patients met the criteria, and 21 were successfully contacted. Of those contacted, the median age at surgery was 67 years (range 53-81 years) and at the time of the survey was 75 years (range 63-84 years) with median follow up of 74 months (range 36-127 years). Preoperatively, 12 patients (57.1%) had urethral hypermobility and 13 patients (61.9%) had mixed urinary incontinence. Eight patients (38.1%) had concomitant sling excision with five of those combined with urethrolysis at the time of the salvage operation. Patient Global Impression of Improvement success was noted in 16 patients (76.2%). A total of 11 patients (52.4%) were dry or had slight incontinence by the Incontinence Severity Index. One patient required additional anti-incontinence surgery (4.8%). A total of 18 patients (85.7%) recommended the autologous fascial sling. No statistical impact was noted with sling excision (P = 0.62), mixed urinary incontinence (P = 0.61), age at surgery (P = 0.23), age at follow up (P = 0.15), length of follow up (P = 0.71) or first surgery type (transobturator tape vs retropubic; P = 1.00). CONCLUSIONS: Autologous fascial sling provides reasonable long-term success as a salvage operation for failed midurethral slings.
Assuntos
Terapia de Salvação , Slings Suburetrais , Incontinência Urinária por Estresse/cirurgia , Idoso , Idoso de 80 Anos ou mais , Fáscia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Incontinência Urinária , Procedimentos Cirúrgicos UrológicosRESUMO
Viral pathogens must overcome innate antiviral responses to replicate successfully in the host organism. Some of the mechanisms viruses use to interfere with antiviral responses in the infected cell include preventing detection of viral components, perturbing the function of transcription factors that initiate antiviral responses, and inhibiting downstream signal transduction. RNA viruses with small genomes and limited coding space often express multifunctional proteins that modulate several aspects of the normal host response to infection. One such virus, rotavirus, is an important pediatric pathogen that causes severe gastroenteritis, leading to ~450,000 deaths globally each year. In this review, we discuss the nature of the innate antiviral responses triggered by rotavirus infection and the viral mechanisms for inhibiting these responses.