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1.
Hosp Pediatr ; 10(6): 509-515, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32393515

RESUMO

BACKGROUND AND OBJECTIVES: Rehabilitation after a child's traumatic brain injury (TBI) occurs in hospital, community, and school settings, requiring coordination of care and advocacy by parents. Our objective was to explore Hispanic parents' experiences during child's transitions of care after TBI. METHODS: We conducted this qualitative study using semistructured interviews. We used a convenient sample of Hispanic parents of children hospitalized for a TBI in a single level I trauma center. Thematic content analysis using iterative deductive coding and triangulation with clinical data was conducted to identify barriers and facilitators for transitions of care. RESULTS: Fifteen mothers, mostly from rural areas and with limited English proficiency, participated in the study. Obtaining outpatient rehabilitation was difficult. Barriers included lack of therapists and clinical providers close to home, worsened by insufficient transportation and other support resources; poor understanding of child's illness and treatments; and suboptimal communication with clinicians and school administrators. Facilitators included interpreter use, availability of Spanish written information, and receipt of inpatient rehabilitation. Parents of patients discharged to inpatient rehabilitation reported that observing therapies, receiving school discharge plans by hospital-teachers, and coordination of care were facilitators to access outpatient treatments and to support school return. Parents of children discharged from the hospital from acute care reported need of legal services to obtain school services. CONCLUSIONS: Hispanic parents, especially those with limited English proficiency, can face significant challenges accessing TBI outpatient rehabilitation and school resources for their children. Although barriers are multifactorial, efforts to improve communication, parent's TBI education, and care coordination during transitions of care may facilitate a child's reintegration to the community and school.

2.
J Immigr Minor Health ; 22(3): 433-438, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31989353

RESUMO

Hospital websites are an important resource to patients with limited English proficiency (LEP) seeking information about a facility's language assistance services. We sought to identify the types of such services described on hospital websites in a diverse state and compare them by hospital characteristics. Washington State acute care hospital websites were systematically reviewed in February 2018 for translated content and information about language assistance services. Hospital characteristics included annual admissions and revenue, bed size and the proportion of populations with LEP in the hospital's county. Of 93 hospitals, 10.8% provided translated websites. Interpreter services were mentioned on 81.7% of websites; access required navigation through 1-4 English webpages. Larger bed-size, higher revenue, and more admissions were positively associated with providing language services information (p < 0.01), whereas county-level population with LEP was not (p = 0.17). Many hospital websites are not translated or lack easily accessible information about language assistance services and consequently may not be a useful resource to patients with LEP.

3.
J Pediatr Nurs ; 51: 15-20, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31838221

RESUMO

PURPOSE: The costs facing families after pediatric concussion are not limited to medical expenses for treatment and rehabilitation care. The objective of this research was to examine the economic hardship facing families following concussion. DESIGN AND METHODS: Eighteen youth (10-18 years old) with a diagnosed concussion injury and sixteen parents (13 parent/youth dyads) answered open-ended questions regarding experiences associated with concussion care and recovery, specifically as they related to cost. Participants were recruited from a concussion clinic, social media, and via snowball sampling. Interviews were audio recorded, transcribed verbatim, and coded using deductive qualitative content analysis. RESULTS: In addition to direct health care expenses (e.g. copays and deductibles), families of youth with concussion faced indirect costs associated with tutoring and transportation to medical appointments, in some cases over long distances. Financial cost-sharing for concussion care varied widely across participants. CONCLUSIONS: Lost productivity included parents missing work to care for their child and for travel to appointments. Research that describes costs of care using claims or survey data lack the experiential perspective of the economic burden on families following concussion. PRACTICE IMPLICATIONS: To fully understand the impact of concussion on patients and families, healthcare providers must consider non-monetary costs, such as opportunity costs, transportation required to obtain healthcare, or the productivity cost associated with missed work and school.

4.
Health Equity ; 3(1): 504-511, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637361

RESUMO

Background: Research on disparities in traumatic injury has not been well characterized, limiting understanding of gaps in research and development of successful interventions. We conducted a scoping review to identify and synthesize research on disparities in intentional and unintentional traumatic injuries. Methods: The review was guided by PRISMA Extension for Scoping Reviews. PubMed, PsycINFO, Web of Science, and CINAHL and systematic reviews from 2007 to 2017 were searched. Eligible articles were peer reviewed; conducted in the United States; and reported on clearly defined physical trauma and disparity, defined by Cochrane PROGRESS-Plus criteria. One reviewer assessed article titles and a second reviewer validated the inclusion with a random sample. Abstract and full-text review by two reviewers determined final inclusion. Results: Of 7382 unique articles screened, 653 articles were included; inter-rater agreement was high (K=0.995). Studies reported on disparities in the acute hospital setting (104) or postacute/rehabilitation (86), with fewer focused on prevention (57) and policy development (6). Research methods used were quantitative (593) with 25 intervention studies, qualitative (45), qualitative/quantitative (7), and community-based participatory research (8). Age ranges of included studies were all ages (124), adults (318), pediatric/youth/adolescents (172), and older adults (40). Racial disparities were most commonly measured (439 studies); 38 created a white/nonwhite binary. Other commonly measured disparities were place of residence (122), insurance (111 studies), gender (89), age (75), and socioeconomic status measures (61). Disparities were noted in all of the categories. Studies commonly aggregated all types of traumatic injuries (129) or all types of violence (105). Conclusions: The extant injury literature lacks research on prevention and policy to address disparities. Many studies aggregated types of trauma and patient groups, preventing an understanding of distinctions between groups and potential interventions. Intervention and community-based research strategies were limited. Future research can better specify measurement of understudied equity categories, trauma types and intent, and racial groups.

5.
BMJ Open ; 9(8): e031781, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31462490

RESUMO

OBJECTIVES: Violence towards emergency department healthcare workers is pervasive and directly linked to provider wellness, productivity and job satisfaction. This qualitative study aimed to identify the cognitive and behavioural processes impacted by workplace violence to further understand why workplace violence has a variable impact on individual healthcare workers. DESIGN: Qualitative interview study using a phenomenological approach to initial content analysis and secondary thematic analysis. SETTING: Three different emergency departments. PARTICIPANTS: We recruited 23 emergency department healthcare workers who experienced a workplace violence event to participate in an interview conducted within 24 hours of the event. Participants included nurses (n=9; 39%), medical assistants (n=5; 22%), security guards (n=5; 22%), attending physicians (n=2; 9%), advanced practitioners (n=1; 4%) and social workers (n=1; 4%). RESULTS: Five themes emerged from the data. The first two supported existing reports that workplace violence in healthcare is pervasive and contributes to burn-out in healthcare. Three novel themes emerged from the data related to the objectives of this study: (1) variability in primary cognitive appraisals of workplace violence, (2) variability in secondary cognitive appraisals of workplace violence and (3) reported use of both avoidant and approach coping mechanisms. CONCLUSION: Healthcare workers identified workplace violence as pervasive. Variability in reported cognitive appraisal and coping strategies may partially explain why workplace violence negatively impacts some healthcare workers more than others. These cognitive and behavioural processes could serve as targets for decreasing the negative effect of workplace violence, thereby improving healthcare worker well-being. Further research is needed to develop interventions that mitigate the negative impact of workplace violence.

6.
Trauma Surg Acute Care Open ; 4(1): e000331, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31392282

RESUMO

Background: In response to increasing mass casualty events nationwide, the American College of Surgeons Committee on Trauma developed a bleeding control course (Stop the Bleed) to teach hemorrhage control techniques to laypeople. There is a high level of public interest in learning about injury mitigation, but no study evaluating learners' perspectives after bleeding control training. We sought to evaluate the didactic value of the bleeding control course by analyzing learners' feedback within the framework of adult learning theory. Study design: We analyzed a total of 720 open-ended surveys from 20 regional bleeding control courses taught by a level I trauma center team during a 9-month period. Major themes expressed by learners were organized into a categorical code structure. Keywords identified from free text responses were used to code comments into subthemes. These themes were organized into categories within the framework of adult learning theory. Results: The two primary themes identified from learners' feedback were empowerment and practicality. Respondents reported an overwhelmingly positive experience; 97% of participants would recommend the course to others. The course design (lecture, didactics and hands-on activities) was cited as a positive element of the course. Participants felt empowered and prepared to act and help others during mass emergency events. Actionable items for future course improvement were identified. Conclusion: Themes from learners' feedback fit within the framework of adult learning theory. These findings highlight the bleeding control course as an empowering experience and a practical and engaging approach to teaching hemorrhage mitigation to the public. Level of evidence: Level V, qualitative analysis.

7.
BMJ Open Qual ; 8(2): e000506, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31206057

RESUMO

Discomfort in the hospitalised patient continues to be one of the healthcare system's greatest challenges to positive patient outcomes. The patients' ability to focus on healing is impaired by discomforts such as pain, nausea and anxiety. Alternative, non-pharmacological therapies have shown to be effective in reducing discomfort and managing pain, complementing analgesic agents and optimising pain therapy modalities. This multi-cycle project is aimed to assess the effect of alternative therapies on inpatient, progressive care patients who reported discomfort or little to no relief in discomfort from prescribed analgesics and adjuvant agents. In the first Plan Do Study Act (PDSA) cycle, patients who reported discomfort were offered aromatherapy or visual relaxation DVDs. In the second PDSA cycle, patients were offered a comfort menu that consisted of multiple alternative interventions such as aromatherapy, ice or heat and ambulation. During each cycle, participants completed a survey measuring comfort levels before and after patient-selected alternative intervention(s) were administered. In the first PDSA cycle, 88% of patients reported an increase in comfort level after the intervention, and 97% reported an interest in using alternative therapy again. In the second PDSA cycle, 47% reported increased comfort, and 89% indicated a willingness to try alternative therapies again for improvement of comfort level. Overall, the quality improvement project increased the level of comfort reported by hospitalised patients, creating a gateway to comfort with less emphasis on prescribed analgesic medications.

8.
South Med J ; 112(3): 159-163, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30830229

RESUMO

OBJECTIVES: Quality improvement in geriatric trauma depends on timely identification of frailty, yet little is known about providers' knowledge and beliefs about frailty assessment. This study sought to understand trauma providers' understanding, beliefs, and practices for frailty assessment. METHODS: We developed a 20-question survey using the Health Belief Model of health behavior and surveyed physicians, advanced practice providers, and trainees on the trauma services at a single institution that does not use formal frailty screening of all injured seniors. Results were analyzed via mixed methods. RESULTS: One hundred fifty-one providers completed the survey (response rate 92%). Respondents commonly included calendar age as an integral factor in their determinations of frailty but also included a variety of other factors, highlighting limited definitional consensus. Respondents perceived frailty as important to older adult patient outcomes, but assessment techniques were varied because only 24/151 respondents (16%) were familiar with current formal frailty assessment tools. Perceived barriers to performing a formal frailty screening on all injured older adults included the burdensome nature of assessment tools, insufficient training, and lack of time. When prompted for solutions, 20% of respondents recommended automation of the screening process by trained, dedicated team members. CONCLUSIONS: Providers seem to recognize the impact that a diagnosis of frailty has on outcomes, but most lack a working knowledge of how to assess for frailty syndrome. Some providers recommended screening by designated, formally trained personnel who could notify decision makers of a positive screen result.


Assuntos
Atitude do Pessoal de Saúde , Fragilidade/diagnóstico , Ferimentos e Lesões/terapia , Adulto , Idoso , Anestesiologistas , Competência Clínica , Cuidados Críticos , Medicina de Emergência , Bolsas de Estudo , Feminino , Idoso Fragilizado , Avaliação Geriátrica , Geriatras , Médicos Hospitalares , Humanos , Internato e Residência , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Enfermeiras Anestesistas , Profissionais de Enfermagem , Cirurgiões Ortopédicos , Assistentes Médicos , Cirurgiões
9.
Health Aff (Millwood) ; 38(3): 473-481, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30830825

RESUMO

Assisters provide in-person and phone-based support to help consumers narrow their plan options on the Affordable Care Act's health insurance Marketplaces. We elicited the perspectives of a national sample of thirty-two assisters from ten states on consumer plan selection and available Marketplace decision support tools (for example, total cost estimators and provider network look-up tools). Assisters identified several shortcomings that limited their use of decision support tools, such as nonspecific cost estimates and inaccurate provider network data. Assisters instead provided individualized cost estimates, called provider offices to verify network coverage, and found innovative strategies to help consumers access care affordably under their chosen plan. Two priorities emerged for optimizing consumers' Marketplace insurance selection process: improve the quality of data used in decision support tools and invest in assister programs. Assister strategies should be a benchmark for improving decision support tools, with lessons to be learned for future tool development.

10.
Health Soc Work ; 44(2): 113-122, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30855682

RESUMO

The perspective of homeless adults on their health care service utilization is not well studied. This article describes a study that used in-depth, semistructured interviews with 18 individuals to highlight the viewpoints of homeless people who are frequent users of the emergency department (ED) about the influence of life events on service utilization. Participants reported high levels of pain and comorbid psychiatric, substance use, and medical conditions. They also reported an identifiable pattern of health care utilization, often centered on a crisis event, influenced by high perceived medical needs, inability to cope after crisis, predisposing vulnerability from social determinants of health, and health care system factors. A social work case management intervention often led to a period of stability and use of ED alternatives. Modifiable targets for intervention at the health care system and local levels include improving trust and convenience of ED alternatives, enhancing consistency of care at ED-alternative sites, and educating those at risk of frequent ED use about community alternatives.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Pessoas em Situação de Rua/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Estresse Psicológico/psicologia , Comorbidade , Feminino , Acesso aos Serviços de Saúde , Pessoas em Situação de Rua/psicologia , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade
11.
Matern Child Nutr ; 15(3): e12782, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30676696

RESUMO

Food insecurity and poor infant and young child feeding (IYCF) practices contribute to undernutrition. The Kanyakla Nutrition Program was developed in rural Kenya to provide knowledge alongside social support for recommended IYCF practices. Utilizing a social network approach, the Kanyakla Nutrition Program trained community health workers (CHWs) to engage mothers, fathers, and grandparents in nutrition education and discussions about strategies to provide instrumental, emotional, and information support within their community. The 12-week programme included six sessions and was implemented on Mfangano Island, Kenya, in 2014-2015. We analysed intervention effects on (a) nutrition knowledge among community members or CHWs and (2) IYCF practices among children 1-3 years. Nutrition knowledge was assessed using a postintervention comparison among intervention (community, n = 43; CHW, n = 22) and comparison groups (community, n = 149; CHW, n = 64). We used a quasi-experimental design and difference-in-difference to assess IYCF indicators using dietary recall data from an ongoing cohort study among intervention participants (n = 48) with individuals living on Mfangano Island where the intervention was not implemented (n = 178) before the intervention, within 1 month postintervention, and 6 months postintervention. Findings showed no effect of the intervention on IYCF indicators (e.g., dietary diversity and meal frequency), and less than 15% of children met minimum acceptable diet criteria at any time point. However, knowledge and confidence among community members and CHWs were significantly higher 2 years postintervention. Thus, a social network approach had an enduring effect on nutrition knowledge, but no effects on improved IYCF practices.


Assuntos
Cuidadores/educação , Educação em Saúde/métodos , Conhecimentos, Atitudes e Prática em Saúde , Fenômenos Fisiológicos da Nutrição do Lactente , Apoio Social , Adulto , Pré-Escolar , Estudos de Coortes , Agentes Comunitários de Saúde , Pai/educação , Feminino , Humanos , Lactente , Quênia , Masculino , Mães/educação , Estado Nutricional , Avaliação de Programas e Projetos de Saúde , População Rural
12.
J Burn Care Res ; 40(2): 202-210, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30239737

RESUMO

Little is understood about the inpatient experience from the burn patients' perspectives. Rather, hospitals emphasize quantitative feedback as part of the ongoing process improvement. Comments returned with the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) administrative survey may provide important patient perspectives. They analyzed quantitative and qualitative HCAHPS data to identify areas for care improvement. They reviewed our burn center HCAHPS results over 2 years. They analyzed "top-box" result in each defined HCAHPS category, which is the most frequently reported best result in each composite, including survey scores ≥9 (out of 10). They performed qualitative content analysis of open-text responses via a HIPAA-compliant analysis software. They developed a hierarchy of major expressed themes and organized them using HCAHPS-validated satisfaction domains. A total of 610 inpatient HCAHPS surveys (21% response rate) were returned. Seventy-five percent of respondents ranked their burn center as ≥9 (out of 10) in care scores. Content analysis identified three main components of the inpatient experience: 1) provider/nurse communication, 2) hospital environment, and 3) the discharge experience. Caring, respect, handoff coordination, explanations, listening, and confidence in provider constituted the six key communication themes. Patients generally reported that burn providers listened to their concerns, but others requested clearer explanations of their condition and care. Responses about hospital environment highlighted excessive noise and disrupted sleep, and variable responses related to cleanliness. Challenges in the discharge experience included difficulties procuring wound care supplies and discharge medications. Qualitative data from HCAHPS helped identify major target areas for burn center performance improvement. Analysis of HCAHPS direct patient feedback is useful in process improvement, whereas numerical data alone do not provide sufficient actionable information.

13.
J Racial Ethn Health Disparities ; 6(2): 335-344, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30276637

RESUMO

OBJECTIVE: This study compares characteristics of American Indian/Alaska Natives (AI/AN) and non-Hispanic Whites (NHW) hospitalized for traumatic injury and examines the effect of race on hospital disposition. METHODS: Using 2007-2014 National Trauma Data Bank data, we described differences in demographic and injury characteristics between AI/AN (n = 39,656) and NHWs (n = 3,309,484) hospitalized with traumatic injuries. Multivariable regressions, adjusted for demographic and injury characteristics, compared in-hospital mortality and the risk of discharge to different dispositions (inpatient rehabilitation/long-term care facility, skilled nursing facility, home with home health services) rather than home between AI/AN and NHW patients. RESULTS: Compared to NHWs, a higher proportion of AI/ANs were age 19-44 (49% versus 27%) years and hospitalized with assault-related injuries (25% versus 5%). AI/ANs had lower odds of dying than NHWs during hospitalization (adjusted odds ratio (aOR) 0.72, 95% CI 0.63-0.84). However, AI/ANs also had lower odds than NHWs to discharge to locations with additional health services even after controlling for injury severity (inpatient rehabilitation/long-term care facilities aOR 0.79, 95% CI 0.67-0.93; skilled nursing facility aOR 0.70, 95% CI 0.49-0.98; home with home health services aOR 0.62, 95% CI 0.49-0.79). CONCLUSIONS: Injury patterns and acute hospitalization outcomes were significantly different for AI/ANs compared to NHWs. Injury prevention strategies targeting AI/ANs should reflect these differential injury patterns. Outcomes such as disability and access to rehabilitation services should be included when considering the burden of injury among AI/AN communities.

14.
Health Serv Res ; 54(2): 337-345, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30507042

RESUMO

OBJECTIVES: To compare health care costs and service utilization associated with mild traumatic brain injury (mTBI) in rural and urban commercially insured children. DATA SOURCE: MarketScan Commercial Claims and Encounters Data, 2007-2011. STUDY DESIGN: We compared health care costs and outpatient encounters for physical/occupational therapy, speech therapy, and psychiatry/psychology encounters 180 days after mTBI among rural versus urban children (<18 years). PRINCIPAL FINDINGS: A total of 387 846 children had mTBI, with 13 percent residing in rural areas. Adjusted mean total health care costs in the 180 days after mTBI were $2778 (95% CI: 2660-2897) among rural children, compared to $2499 (95% CI: 2471-2528) among urban children (adjusted cost ratio 1.11, 95% CI 1.06-1.16). Rural-urban differences in utilization for specific services were also found. CONCLUSIONS: Total health care costs were higher for rural compared to urban children despite lower utilization of certain services. Differences in health service utilization may exacerbate geographic disparities in adverse outcomes associated with mTBI.


Assuntos
Concussão Encefálica/terapia , Gastos em Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adolescente , Concussão Encefálica/epidemiologia , Concussão Encefálica/reabilitação , Criança , Pré-Escolar , Comorbidade , Feminino , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Serviços de Saúde/economia , Serviços de Saúde/estatística & dados numéricos , Humanos , Lactente , Masculino , Características de Residência/estatística & dados numéricos , Estudos Retrospectivos , Fatores Socioeconômicos , Índices de Gravidade do Trauma
15.
Res Soc Work Pract ; 28(3): 254-264, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30220827

RESUMO

Background: Early career faculty experiences and perspectives on transdisciplinary research are important yet understudied. Methods: Assistant professors at 50 top-ranked social work programs completed an online survey assessing perspectives on the salience of transdisciplinary training in their field, obstacles to or negative impacts of transdisciplinary training, and current environments. Content analysis and descriptive statistics were used. Results: A large majority of all participants (N » 118) believed that transdisciplinary research is important, that greater training is needed, and that they are relatively well prepared in related skill sets. They are expected to build cross-disciplinary collaborations, yet only a small minority believed that social work researchers are nationally recognized as important collaborators, or that they are prepared to navigate tensions on research teams. Conclusions: We offer a multilevel framework of structural and training supports needed to realize transdisciplinary research in social work with relevance to other disciplines.

16.
J Am Assoc Nurse Pract ; 30(9): 499-510, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30113534

RESUMO

BACKGROUND AND PURPOSE: Nurse practitioners (NPs) frequently treat acute conditions presenting in children and adolescents in the outpatient setting. No evidence-based guidance exists pertaining to the treatment of concussion with medications. The purpose of this study was to examine recommendations by NPs for pharmacotherapy of acute symptoms for adolescent concussion. METHODS: This is a secondary analysis of data from a web-based census survey of all licensed NPs in Oregon and Washington State, where they practice as independent providers with prescriptive authority. Based on a standardized adolescent patient scenario video, NPs were asked to indicate prescription or nonprescription medication recommendations for concussion symptoms. Open-ended descriptions of medication recommendations were coded, summarized, and described. CONCLUSIONS: In narrative text, 78.4% of the 991 respondents recommended at least one type of prescription or nonprescription medication. Prescription medications (recommended by 17.2%) included antiemetics and antimigraine medications; nonprescription medications (recommended by 75.5%) included nonsteroidal anti-inflammatory drugs, over-the-counter pain relievers, and herbal medications. Pharmacotherapy recommendations varied by NP practice setting and rurality. IMPLICATIONS FOR PRACTICE: Nurse practitioners have full prescriptive authority in many states. No guidelines inform medication use in managing acute concussion symptoms, yet many providers recommend their use.


Assuntos
Concussão Encefálica/tratamento farmacológico , Tomada de Decisões , Tratamento Farmacológico/métodos , Profissionais de Enfermagem/tendências , Adolescente , Adulto , Prescrições de Medicamentos/enfermagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oregon , Inquéritos e Questionários , Washington
17.
Nucleic Acids Res ; 46(17): 8689-8699, 2018 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-30102385

RESUMO

DEAD-box proteins are an essential class of enzymes involved in all stages of RNA metabolism. The study of DEAD-box proteins is challenging in a native setting since they are structurally similar, often essential and display dosage sensitivity. Pharmacological inhibition would be an ideal tool to probe the function of these enzymes. In this work, we describe a chemical genetic strategy for the specific inactivation of individual DEAD-box proteins with small molecule inhibitors using covalent complementarity. We identify a residue of low conservation within the P-loop of the nucleotide-binding site of DEAD-box proteins and show that it can be mutated to cysteine without a substantial loss of enzyme function to generate electrophile-sensitive mutants. We then present a series of small molecules that rapidly and specifically bind and inhibit electrophile-sensitive DEAD-box proteins with high selectivity over the wild-type enzyme. Thus, this approach can be used to systematically generate small molecule-sensitive alleles of DEAD-box proteins, allowing for pharmacological inhibition and functional characterization of members of this enzyme family.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Proteína DEAD-box 58/química , RNA Helicases DEAD-box/química , Proteína Oncogênica pp60(v-src)/química , Proteínas de Saccharomyces cerevisiae/química , Acrilamidas/síntese química , Acrilamidas/metabolismo , Acrilatos/síntese química , Acrilatos/metabolismo , Monofosfato de Adenosina/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Substituição de Aminoácidos , Sítios de Ligação , Clonagem Molecular , Crotonatos/síntese química , Crotonatos/metabolismo , Cristalografia por Raios X , Proteína DEAD-box 58/antagonistas & inibidores , Proteína DEAD-box 58/genética , Proteína DEAD-box 58/metabolismo , RNA Helicases DEAD-box/antagonistas & inibidores , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Humanos , Cinética , Modelos Moleculares , Proteína Oncogênica pp60(v-src)/antagonistas & inibidores , Proteína Oncogênica pp60(v-src)/genética , Proteína Oncogênica pp60(v-src)/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
18.
Int J Occup Environ Health ; 24(1-2): 1-6, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29902943

RESUMO

BACKGROUND: Due to the lack of standard industrial hygiene sampling protocols for collection of nano-scale materials, sampling inlet device selection is left to individual researchers and professionals. OBJECTIVE: The objective of this study was to compare nano-scale aspiration efficiency for common inlet configurations with that of an open-ended sampler tube that is a commonly used inlet for direct reading instruments such as a condensation particle counter. METHODS: A polydisperse aerosol was generated using an electric motor as the aerosol source. Typical aerosols generated by this method produced particles with geometric mean mobility diameters of approximately 30 nm with geometric standard deviations of approximately 2. Comparison of raw particle counts in size ranges measured with a scanning mobility particle analyzer was made by determining the fractional difference between the selected inlet and that of the open-ended tube. RESULTS: Particle size distributions were nearly identical for all inlet types. The same held true for numbers of particles collected with the exception that the needle inlet was highly variable. CONCLUSIONS: When completing air monitoring for nano-scale materials, inlets on most collection devices (filters, tubing) do not impact aspiration efficiency. This means that it is not necessary to match inlet configurations when using multiple methods to collect and analyze nano-scale materials.


Assuntos
Monitoramento Ambiental/instrumentação , Nanopartículas/análise , Aerossóis , Monitoramento Ambiental/métodos , Desenho de Equipamento , Exposição por Inalação/análise , Tamanho da Partícula
19.
Org Lett ; 20(7): 1802-1805, 2018 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-29557662

RESUMO

The Brassica rapa oxidosqualene cyclase Bra032185 makes 60% astertarone A (1) and 20 minor triterpenes (0.1-11%). Mechanistic analysis indicates the absence of an enol intermediate to generate the 4 S epimer of 1, unless workup involves saponification. Bra032185 and its closest Arabidopsis thaliana homologue diverged markedly in product profiles over a short evolutionary distance, while developing opposite C18 configurations. Active-site residue comparison of Bra032185 with friedelin and shionone synthases suggests convergent evolution to 3-ketotriterpenes.

20.
Org Biomol Chem ; 16(8): 1263-1271, 2018 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-29308815

RESUMO

The emergence of nucleosides is an important, but poorly understood, element of the origins of life. We show that 2,4,6-triaminopyrimidine (TAP), a possible ancestral nucleobase of RNA, is glycosylated in water by non-ribose sugars in yields comparable to those previously reported for its reaction with ribose. The various sugars surveyed include ketoses and aldoses; tetroses, pentoses, and hexoses and are neutral, anionic, or cationic. Though they vary greatly in structure and properties, the data show that all sugars tested form glycosides with TAP. The structures of the eight TAP glycosides formed with glucose and two of its derivatives, glucose-6-phosphate and N-acetylglucosamine, were found to be ß-pyranosides with the glycosylation site on TAP varying with sugar identity. Our results suggest that prebiotic nucleoside formation would not have been restricted to ribose if ancestral RNA (or proto-RNA) utilized TAP and/or other proto-nucleobases with similar reactivities, and that the ability to form higher-order structures may have influenced proto-RNA monomer selection.


Assuntos
Glicosilação , Nucleosídeos/biossíntese , Origem da Vida , Pirimidinas/química , Monossacarídeos/química , Nucleosídeos/química , RNA/química , Açúcares/química
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