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1.
Am J Kidney Dis ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38851446

RESUMO

RATIONALE & OBJECTIVE: Developing strategies to improve home dialysis use requires a comprehensive understanding of barriers. We sought to identify the most important barriers to home dialysis use from the perspective of patients, care partners, and providers. STUDY DESIGN: This is a convergent parallel mixed-methods study. SETTING & PARTICIPANTS: We convened a seven-member advisory board of patients, care partners, and providers who collectively developed lists of major patient/care partner-perceived barriers and provider-perceived barriers to home dialysis. We used these lists to develop a survey that was distributed to patients, care partners, and providers-through the American Association of Kidney Patients and the National Kidney Foundation. The surveys asked participants to: 1) rank their top three major barriers (quantitative); and 2) describe barriers to home dialysis (qualitative). ANALYTICAL APPROACH: We compiled a list of the top three patient/care partner-perceived and top three provider-perceived barriers (quantitative) and conducted a directed content analysis of open-ended survey responses (qualitative). RESULTS: There were 522 complete responses (233 providers; 289 patients/care partners). The top three patient/care partner-perceived barriers were: fear of performing home dialysis; lack of space; and the need for home-based support. The top three provider-perceived barriers were: poor patient education; limited mechanisms for home-based support staff, mental health, and education; and lack of experienced staff. We identified nine themes through qualitative analysis: limited education; financial disincentives; limited resources; high burden of care; built environment/structure of care delivery that favor in-center hemodialysis; fear and isolation; perceptions of inequities in access to home dialysis; provider perspectives about patients; and patient/provider resiliency. LIMITATIONS: This was an online survey that is subject to non-response bias. CONCLUSIONS: The top three barriers to home dialysis for patient/care partners and providers incompletely overlap, suggesting the need for diverse strategies that simultaneously address patient-perceived barriers at home and provider-perceived barriers in the clinic.

2.
J Gen Intern Med ; 38(2): 508-512, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36163531

RESUMO

A staggering number of individuals live with cognitive decline. Primary care providers are ideally situated to detect the first signs of cognitive decline, but many persons remain undiagnosed. This limits their access to appropriate care. Unfortunately, the timely diagnosis of mild cognitive impairment or dementia in primary care is difficult to achieve. There is a great need for interventions to address this problem. This article applies an implementation science framework, the Behavioral Change Wheel, to evaluate the factors that influence detection of cognitive impairment in primary care and proposes candidate interventions for future study.


Assuntos
Disfunção Cognitiva , Demência , Humanos , Demência/diagnóstico , Disfunção Cognitiva/diagnóstico
3.
J Gen Intern Med ; 38(16): 3509-3516, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37349639

RESUMO

BACKGROUND: Little is known about the prevalence or chronicity of prescriptions of central nervous system-active (CNS-active) medications in older Veterans. OBJECTIVE: We sought to describe (1) the prevalence and trends in prescription of CNS-active medications in older Veterans over time; (2) variation in prescriptions across high-risk groups; and (3) where the prescription originated (VA or Medicare Part D). DESIGN: Retrospective cohort study from 2015 to 2019. PARTICIPANTS: Veterans age ≥ 65 enrolled in the Medicare and the VA residing in Veterans Integrated Service Network 4 (incorporating Pennsylvania and parts of surrounding states). MAIN MEASURES: Drug classes included antipsychotics, gabapentinoids, muscle relaxants, opioids, sedative-hypnotics, and anticholinergics. We described prescribing patterns overall and in three subgroups: Veterans with a diagnosis of dementia, Veterans with high predicted utilization, and frail Veterans. We calculated both prevalence (any fill) and percent of days covered (chronicity) for each drug class, and CNS-active polypharmacy (≥ 2 CNS-active medications) rates in each year in these groups. KEY RESULTS: The sample included 460,142 Veterans and 1,862,544 person-years. While opioid and sedative-hypnotic prevalence decreased, gabapentinoids exhibited the largest increase in both prevalence and percent of days covered. Each subgroup exhibited different patterns of prescribing, but all had double the rates of CNS-active polypharmacy compared to the overall study population. Opioid and sedative-hypnotic prevalence was higher in Medicare Part D prescriptions, but the percent of days covered of nearly all drug classes was higher in VA prescriptions. CONCLUSIONS: The concurrent increase of gabapentinoid prescribing paralleling a decrease in opioid and sedative-hypnotics is a new phenomenon that merits further evaluation of patient safety outcomes. In addition, we found substantial potential opportunities for deprescribing CNS-active medications in high-risk groups. Finally, the increased chronicity of VA prescriptions versus Medicare Part D is novel and should be further evaluated in terms of its mechanism and impact on Medicare-VA dual users.


Assuntos
Medicare Part D , Veteranos , Humanos , Idoso , Estados Unidos/epidemiologia , Analgésicos Opioides/uso terapêutico , Estudos Retrospectivos , Prevalência , United States Department of Veterans Affairs , Hipnóticos e Sedativos/uso terapêutico , Prescrições de Medicamentos , Sistema Nervoso Central
4.
J Nurs Care Qual ; 38(3): 286-292, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36857291

RESUMO

BACKGROUND: High-quality transitional care at discharge is essential for improved patient outcomes. Registered nurses (RNs) play integral roles in transitions; however, few receive structured training. PURPOSE: We sought to create, implement, and evaluate an evidence-informed nursing transitional care coordination curriculum, the Transitions Nurse Training Program (TNTP). METHODS: We conceptualized the curriculum using adult learning theory and evaluated with the New World Kirkpatrick Model. Self-reported engagement, satisfaction, acquired knowledge, and confidence were assessed using surveys. Clinical and communication skills were evaluated by standardized patient assessment and behavior sustainment via observation 6 to 9 months posttraining. RESULTS: RNs reported high degrees of engagement, satisfaction, knowledge, and confidence and achieved a mean score of 92% on clinical and communication skills. Posttraining observation revealed skill sustainment (mean score 98%). CONCLUSIONS: Results suggest TNTP is effective for creating engagement, satisfaction, acquired and sustained knowledge, and confidence for RNs trained in transitional care.


Assuntos
Currículo , Enfermeiras e Enfermeiros , Adulto , Humanos , Aprendizagem , Alta do Paciente , Competência Clínica
5.
BMC Biol ; 19(1): 257, 2021 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-34863182

RESUMO

BACKGROUND: The evolutionary history of cell types provides insights into how morphological and functional complexity arose during animal evolution. Photoreceptor cell types are particularly broadly distributed throughout Bilateria; however, their evolutionary relationship is so far unresolved. Previous studies indicate that ciliary photoreceptors are homologous at least within chordates, and here, we present evidence that a related form of this cell type is also present in echinoderm larvae. RESULTS: Larvae of the purple sea urchin Strongylocentrotus purpuratus have photoreceptors that are positioned bilaterally in the oral/anterior apical neurogenic ectoderm. Here, we show that these photoreceptors express the transcription factor Rx, which is commonly expressed in ciliary photoreceptors, together with an atypical opsin of the GO family, opsin3.2, which localizes in particular to the cilia on the cell surface of photoreceptors. We show that these ciliary photoreceptors express the neuronal marker synaptotagmin and are located in proximity to pigment cells. Furthermore, we systematically identified additional transcription factors expressed in these larval photoreceptors and found that a majority are orthologous to transcription factors expressed in vertebrate ciliary photoreceptors, including Otx, Six3, Tbx2/3, and Rx. Based on the developmental expression of rx, these photoreceptors derive from the anterior apical neurogenic ectoderm. However, genes typically involved in eye development in bilateria, including pax6, six1/2, eya, and dac, are not expressed in sea urchin larval photoreceptors but are instead co-expressed in the hydropore canal. CONCLUSIONS: Based on transcription factor expression, location, and developmental origin, we conclude that the sea urchin larval photoreceptors constitute a cell type that is likely homologous to the ciliary photoreceptors present in chordates.


Assuntos
Células Fotorreceptoras , Ouriços-do-Mar , Animais , Ectoderma/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Larva , Células Fotorreceptoras/metabolismo , Ouriços-do-Mar/genética , Ouriços-do-Mar/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
6.
Health Care Manage Rev ; 47(2): 109-114, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33181554

RESUMO

BACKGROUND: Ensuring safe transitions of care around hospital discharge requires effective relationships and communication between health care teams. Relational coordination (RC) is a process of communicating and relating for the purpose of task integration that predicts desirable outcomes for patients and providers. RC can be measured using a validated survey. PURPOSE: The aim of the study was to demonstrate the application of RC practices within the rural Transitions Nurse Program (TNP), a nationwide transitions of care intervention for Veterans, and assess relationships and mechanisms for developing RC in teams. METHODOLOGY/APPROACH: TNP implemented practices expected to support RC. These included creation of a transition nurse role, preimplementation site visits, process mapping to understand workflow, creation of standardized communication templates and protocols, and inclusion of teamwork and shared accountability in job descriptions and annual reviews. We used the RC Survey to measure RC for TNP health care teams. Associations between the months each site participated in TNP, number of Veterans enrolled, and adherence to the TNP intervention were assessed as possible mechanisms for developing high RC using Spearman (rs) correlations. RESULTS: The RC Survey was completed by 44 providers from 11 Veterans Health Administration medical centers. RC scores were high across sites (mean = 4.19; 1-5 Likert scale) and were positively correlated with months participating in TNP (rs = .66) and number of enrollees (rs = .63), but not with adherence to the TNP intervention (rs = .12). PRACTICE IMPLICATIONS: The impact of practices to support RC can be assessed using the RC Survey. Our findings suggest scale-up time is a likely mechanism to the development of high-quality relationships and communication within teams.


Assuntos
Transferência de Pacientes , Veteranos , Humanos , Equipe de Assistência ao Paciente , População Rural , Estados Unidos , United States Department of Veterans Affairs
7.
Med Care ; 59(1): 53-57, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32925464

RESUMO

OBJECTIVE: The objective of this study was to analyze new telehealth benefits offered by Medicare Advantage (MA) plans in 2020 and examine plan characteristics associated with the provision of the new telehealth benefits. RESEARCH DESIGN: Using publicly available data from the Centers for Medicare and Medicaid Services, we identified unique MA plans with at least 1 enrollee in January 2020. We examined whether plans offered any new telehealth benefits in 2020, the 20 most common types of telehealth services covered, and cost-sharing. Next, we used multivariable logistic regression to identify associations between offering any telehealth benefits and plan characteristics. We conducted a similar analysis for each of the 3 most commonly covered telehealth services. RESULTS: Of 2992 unique MA plans, 58.1% offered new telehealth benefits in 2020. The most frequently covered services were primary care, mental health, and urgent care. Coverage for other types of services was limited. Our multivariable logistic regression showed that offering any new telehealth benefits was not more common among plans in rural areas, but was more likely among national plans, those with a monthly premium, those with >3540 enrollees, and those with a star rating of 4.0-4.5. The new telehealth benefits were less likely to be provided by for-profit plans. Overall, findings remained similar when analyzed according to the type of services. CONCLUSIONS: MA plans are embracing new telehealth benefits, but there is room for improvement. Policymakers should consider how to accelerate the adoption curve of telehealth in MA plans.


Assuntos
Assistência Ambulatorial , Benefícios do Seguro/estatística & dados numéricos , Medicare Part C/estatística & dados numéricos , Saúde Mental , Atenção Primária à Saúde , Telemedicina , Idoso , Estudos Transversais , Humanos , Estados Unidos
8.
J Gen Intern Med ; 36(8): 2251-2258, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33532965

RESUMO

BACKGROUND: Adverse outcomes are common in transitions from hospital to skilled nursing facilities (SNFs). Gaps in transitional care processes contribute to these outcomes, but it is unclear whether hospital and SNF clinicians have the same perception about who is responsible for filling these gaps in care transitions. OBJECTIVE: We sought to understand the perspectives of hospital and SNF clinicians on their roles and responsibilities in transitional care processes, to identify areas of congruence and gaps that could be addressed to improve transitions. DESIGN: Semi-structured interviews with interdisciplinary hospital and SNF providers. PARTICIPANTS: Forty-one clinicians across 3 hospitals and 3 SNFs including nurses (8), social workers (7), physicians (8), physical and occupational therapists (12), and other staff (6). APPROACH: Using team-based approach to deductive analysis, we mapped responses to the 10 domains of the Ideal Transitions of Care Framework (ITCF) to identify areas of agreement and gaps between hospitals and SNFs. KEY RESULTS: Although both clinician groups had similar conceptions of an ideal transitions of care, their perspectives included significant gaps in responsibilities in 8 of the 10 domains of ITCF, including Discharge Planning; Complete Communication of Information; Availability, Timeliness, Clarity and Organization of Information; Medication Safety; Educating Patients to Promote Self-Management; Enlisting Help of Social and Community Supports; Coordinating Care Among Team Members; and Managing Symptoms After Discharge. CONCLUSIONS: As hospitals and SNFs increasingly are held jointly responsible for the outcomes of patients transitioning between them, clarity in roles and responsibilities between hospital and SNF staff are needed. Improving transitions of care may require site-level efforts, joint hospital-SNF initiatives, and national financial, regulatory, and technological fixes. In the meantime, building effective hospital-SNF partnerships is increasingly important to delivering high-quality care to a vulnerable older adult population.


Assuntos
Instituições de Cuidados Especializados de Enfermagem , Cuidado Transicional , Idoso , Hospitais , Humanos , Alta do Paciente , Transferência de Pacientes
9.
Arch Phys Med Rehabil ; 102(5): 984-998, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32966808

RESUMO

OBJECTIVE: To describe how different key stakeholders (ie, interprofessional clinical care team and patients) perceive their role in promoting in-hospital mobility by systematically synthesizing qualitative literature. DATA SOURCES: PubMed, Ovid MEDLINE, Ovid PsychInfo, and Cumulative Index to Nursing and Allied Health were searched using terms relevant to mobility, hospitalization, and qualitative research. A total of 510 unique articles were retrieved and screened for eligibility. STUDY SELECTION: Eligible qualitative studies included stakeholder perspectives on in-hospital mobility, including patients, nursing staff, rehabilitation staff, and physicians. Eleven articles remained after inclusion/exclusion criteria were applied. DATA EXTRACTION: At least 2 authors independently read, coded, and derived themes from each study. We used a team-based inductive approach to thematic synthesis informed by critical realism and the socioecological model. Reciprocal translation unified convergent and divergent constructs across primary studies. Investigator triangulation enhanced interpretation. DATA SYNTHESIS: Three primary themes emerged: (1) patient, family, and clinician expectations shape roles in in-hospital mobility; (2) stakeholders' role in mobility depends on hospital environment, infrastructure, culture, and resources; and (3) teamwork creates successful in-hospital mobility, but lack of coordination and cooperation leads to delay in mobilizing. Studies suggested that while mobility is an essential construct in the professional role of clinicians and in the personal identity of patients, the ability of stakeholders to realize their role in mobility is highly dependent on the hospital physical and cultural environment, administrative support, clarity in professional roles, and teamwork. CONCLUSIONS: Interventions designed to address the problem of low hospital mobility should take a systems approach and consider allocation of resources, clarity around professional responsibilities, and elevation of patient and clinician expectations surrounding mobility.


Assuntos
Idoso Fragilizado , Fragilidade/reabilitação , Hospitalização , Limitação da Mobilidade , Comportamento Sedentário , Análise de Sistemas , Idoso , Humanos , Pesquisa Qualitativa , Participação dos Interessados
10.
Neurobiol Dis ; 136: 104725, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31911115

RESUMO

Identifying disease-causing pathways and drugs that target them in Parkinson's disease (PD) has remained challenging. We uncovered a PD-relevant pathway in which the stress-regulated heterodimeric transcription complex CHOP/ATF4 induces the neuron prodeath protein Trib3 that in turn depletes the neuronal survival protein Parkin. Here we sought to determine whether the drug adaptaquin, which inhibits ATF4-dependent transcription, could suppress Trib3 induction and neuronal death in cellular and animal models of PD. Neuronal PC12 cells and ventral midbrain dopaminergic neurons were assessed in vitro for survival, transcription factor levels and Trib3 or Parkin expression after exposure to 6-hydroxydopamine or 1-methyl-4-phenylpyridinium with or without adaptaquin co-treatment. 6-hydroxydopamine injection into the medial forebrain bundle was used to examine the effects of systemic adaptaquin on signaling, substantia nigra dopaminergic neuron survival and striatal projections as well as motor behavior. In both culture and animal models, adaptaquin suppressed elevation of ATF4 and/or CHOP and induction of Trib3 in response to 1-methyl-4-phenylpyridinium and/or 6-hydroxydopamine. In culture, adaptaquin preserved Parkin levels, provided neuroprotection and preserved morphology. In the mouse model, adaptaquin treatment enhanced survival of dopaminergic neurons and substantially protected their striatal projections. It also significantly enhanced retention of nigrostriatal function. These findings define a novel pharmacological approach involving the drug adaptaquin, a selective modulator of hypoxic adaptation, for suppressing Parkin loss and neurodegeneration in toxin models of PD. As adaptaquin possesses an oxyquinoline backbone with known safety in humans, these findings provide a firm rationale for advancing it towards clinical evaluation in PD.


Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Proteínas de Ciclo Celular/biossíntese , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/prevenção & controle , Piridinas/farmacologia , Quinolinas/farmacologia , Fator de Transcrição CHOP/metabolismo , Fator 4 Ativador da Transcrição/antagonistas & inibidores , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Células Cultivadas , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxidopamina/toxicidade , Células PC12 , Transtornos Parkinsonianos/induzido quimicamente , Piridinas/uso terapêutico , Quinolinas/uso terapêutico , Ratos , Fator de Transcrição CHOP/antagonistas & inibidores
11.
Development ; 144(19): 3602-3611, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28851710

RESUMO

We have examined regulation of neurogenesis by Delta/Notch signaling in sea urchin embryos. At gastrulation, neural progenitors enter S phase coincident with expression of Sp-SoxC. We used a BAC containing GFP knocked into the Sp-SoxC locus to label neural progenitors. Live imaging and immunolocalizations indicate that Sp-SoxC-expressing cells divide to produce pairs of adjacent cells expressing GFP. Over an interval of about 6 h, one cell fragments, undergoes apoptosis and expresses high levels of activated Caspase3. A Notch reporter indicates that Notch signaling is activated in cells adjacent to cells expressing Sp-SoxC. Inhibition of γ-secretase, injection of Sp-Delta morpholinos or CRISPR/Cas9-induced mutation of Sp-Delta results in supernumerary neural progenitors and neurons. Interfering with Notch signaling increases neural progenitor recruitment and pairs of neural progenitors. Thus, Notch signaling restricts the number of neural progenitors recruited and regulates the fate of progeny of the asymmetric division. We propose a model in which localized signaling converts ectodermal and ciliary band cells to neural progenitors that divide asymmetrically to produce a neural precursor and an apoptotic cell.


Assuntos
Divisão Celular Assimétrica , Embrião não Mamífero/metabolismo , Células-Tronco Neurais/citologia , Neurogênese , Receptores Notch/metabolismo , Ouriços-do-Mar/embriologia , Ouriços-do-Mar/metabolismo , Transdução de Sinais , Animais , Apoptose , Padronização Corporal , Ectoderma/citologia , Ectoderma/metabolismo , Embrião não Mamífero/citologia , Proteínas de Fluorescência Verde/metabolismo , Mitose , Modelos Biológicos , Células-Tronco Neurais/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Fatores de Transcrição SOX/metabolismo
12.
Med Care ; 58(4): 301-306, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31895308

RESUMO

BACKGROUND: The period after transition from hospital to skilled nursing facility (SNF) is high-risk, but variability in outcomes related to transitions across hospitals is not well-known. OBJECTIVES: Evaluate variability in transitional care outcomes across Veterans Health Administration (VHA) and non-VHA hospitals for Veterans, and identify characteristics of high-performing and low-performing hospitals. RESEARCH DESIGN: Retrospective observational study using the 2012-2014 Residential History File, which concatenates VHA, Medicare, and Medicaid data into longitudinal episodes of care for Veterans. SUBJECTS: Veterans aged 65 or older who were acutely hospitalized in a VHA or non-VHA hospital and discharged to SNF; 1 transition was randomly selected per patient. MEASURES: Adverse "transitional care" outcomes were a composite of hospital readmission, emergency department visit, or mortality within 7 days of hospital discharge. RESULTS: Among the 365,942 Veteran transitions from hospital to SNF across 1310 hospitals, the composite outcome rate ranged from 3.3% to 23.2%. In multivariable analysis adjusting for patient characteristics, hospital discharge diagnosis and SNF category, no single hospital characteristic was significantly associated with the 7-day adverse outcomes in either VHA or non-VHA hospitals. Very few high or low-performing hospitals remained in this category across all 3 years. The increased odds of having a 7-day event due to being treated in a low versus high-performing hospital was similar to the odds carried by having an intensive care unit stay during the index admission. CONCLUSIONS: While variability in hospital outcomes is significant, unmeasured care processes may play a larger role than currently measured hospital characteristics in explaining outcomes.


Assuntos
Hospitais de Veteranos , Alta do Paciente/estatística & dados numéricos , Instituições de Cuidados Especializados de Enfermagem/estatística & dados numéricos , Cuidado Transicional/tendências , Idoso , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Medicaid , Medicare , Mortalidade/tendências , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Estados Unidos
13.
Health Care Manage Rev ; 45(4): 353-363, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30418292

RESUMO

BACKGROUND: Hospitalized older adults are increasingly admitted to skilled nursing facilities (SNFs) for posthospital care. However, little is known about how SNFs screen and evaluate potential new admissions. In an era of increasing emphasis on postacute care outcomes, these processes may represent an important target for interventions to improve the value of SNF care. PURPOSE: The aim of this study was to understand (a) how SNF clinicians evaluate hospitalized older adults and make decisions to admit patients to an SNF and (b) the limitations and benefits of current practices in the context of value-based payment reforms. METHODS: We used semistructured interviews to understand the perspective of 18 clinicians at three unique SNFs-including physicians, nurses, therapists, and liaisons. All transcripts were analyzed using a general inductive theme-based approach. RESULTS: We found that the screening and admission processes varied by SNF and that variability was influenced by three key external pressures: (a) inconsistent and inadequate transfer of medical documentation, (b) lack of understanding among hospital staff of SNF processes and capabilities, and (c) hospital payment models that encouraged hospitals to discharge patients rapidly. Responses to these pressures varied across SNFs. For example, screening and evaluation processes to respond to these pressures included gaining access to electronic medical records, providing inpatient physician consultations prior to SNF acceptance, and turning away more complex patients for those perceived to be more straightforward rehabilitation patients. CONCLUSIONS: We found facility behavior was driven by internal and external factors with implications for equitable access to care in the era of value-based purchasing. PRACTICE IMPLICATIONS: SNFs can most effectively respond to these pressures by increasing their agency within hospital-SNF relationships and prioritizing more careful patient screening to match patient needs and facility capabilities.


Assuntos
Pessoal de Saúde , Programas de Rastreamento/normas , Admissão do Paciente/normas , Instituições de Cuidados Especializados de Enfermagem , Cuidados Semi-Intensivos , Aquisição Baseada em Valor , Hospitalização , Humanos , Entrevistas como Assunto , Alta do Paciente , Estados Unidos
14.
Development ; 143(2): 286-97, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26511925

RESUMO

A single origin to the diverse mechanisms of metazoan neurogenesis is suggested by the involvement of common signaling components and similar classes of transcription factors. However, in many forms we lack details of where neurons arise, patterns of cell division, and specific differentiation pathway components. The sea urchin larval nervous system is composed of an apical organ, which develops from neuroepithelium and functions as a central nervous system, and peripheral neurons, which differentiate in the ciliary band and project axons to the apical organ. To reveal developmental mechanisms of neurogenesis in this basal deuterostome, we developed antibodies to SoxC, SoxB2, ELAV and Brn1/2/4 and used neurons that develop at specific locations to establish a timeline for neurogenesis. Neural progenitors express, in turn, SoxB2, SoxC, and Brn1/2/4, before projecting neurites and expressing ELAV and SynB. Using pulse-chase labeling of cells with a thymidine analog to identify cells in S-phase, we establish that neurons identified by location are in their last mitotic cycle at the time of hatching, and S-phase is coincident with expression of SoxC. The number of cells expressing SoxC and differentiating as neurons is reduced in embryos injected with antisense morpholino oligonucleotides to SoxC, SoxB2 or Six3. Injection of RNA encoding SoxC into eggs does not enhance neurogenesis. In addition, inhibition of FGF receptors (SU5402) or a morpholino to FGFR1 reduces expression of SoxC. These data indicate that there are common features of neurogenesis in deuterostomes, and that sea urchins employ developmental mechanisms that are distinct from other ambulacraria.


Assuntos
Embrião não Mamífero/citologia , Larva/citologia , Neurogênese/fisiologia , Ouriços-do-Mar/citologia , Animais , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Larva/metabolismo , Neurogênese/genética , Neurônios/citologia , Neurônios/metabolismo , Ouriços-do-Mar/metabolismo
15.
RNA ; 23(6): 952-967, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28325844

RESUMO

Proteins of the Sm and Sm-like (LSm) families, referred to collectively as (L)Sm proteins, are found in all three domains of life and are known to promote a variety of RNA processes such as base-pair formation, unwinding, RNA degradation, and RNA stabilization. In eukaryotes, (L)Sm proteins have been studied, inter alia, for their role in pre-mRNA splicing. In many organisms, the LSm proteins form two distinct complexes, one consisting of LSm1-7 that is involved in mRNA degradation in the cytoplasm, and the other consisting of LSm2-8 that binds spliceosomal U6 snRNA in the nucleus. We recently characterized the splicing proteins from the red alga Cyanidioschyzon merolae and found that it has only seven LSm proteins. The identities of CmLSm2-CmLSm7 were unambiguous, but the seventh protein was similar to LSm1 and LSm8. Here, we use in vitro binding measurements, microscopy, and affinity purification-mass spectrometry to demonstrate a canonical splicing function for the C. merolae LSm complex and experimentally validate our bioinformatic predictions of a reduced spliceosome in this organism. Copurification of Pat1 and its associated mRNA degradation proteins with the LSm proteins, along with evidence of a cytoplasmic fraction of CmLSm complexes, argues that this complex is involved in both splicing and cytoplasmic mRNA degradation. Intriguingly, the Pat1 complex also copurifies with all four snRNAs, suggesting the possibility of a spliceosome-associated pre-mRNA degradation complex in the nucleus.


Assuntos
Precursores de RNA/genética , Splicing de RNA , RNA Mensageiro/genética , Proteínas de Ligação a RNA/metabolismo , Rodófitas/genética , Rodófitas/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Biologia Computacional/métodos , Imunoprecipitação , Modelos Moleculares , Conformação de Ácido Nucleico , Filogenia , Ligação Proteica , Conformação Proteica , Transporte Proteico , Precursores de RNA/química , Estabilidade de RNA , RNA Mensageiro/química , RNA Nuclear Pequeno/química , RNA Nuclear Pequeno/genética , Proteínas de Ligação a RNA/química , Espectrometria de Massas em Tandem
16.
J Gen Intern Med ; 34(Suppl 1): 58-66, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31098972

RESUMO

OBJECTIVE: Understanding how to successfully implement care coordination programs across diverse settings is critical for disseminating best practices. We describe how we operationalized the Practical Robust Implementation and Sustainability Model (PRISM) to guide the assessment of local context prior to implementation of the rural Transitions Nurse Program (TNP) at five facilities across the Veterans Health Administration (VHA). METHODS: We operationalized PRISM to create qualitative data collection techniques (interview guides, semi-structured observations, and a group brainwriting premortem) to assess local context, the current state of care coordination, and perceptions of TNP prior to implementation at five facilities. We analyzed data using deductive-inductive framework analysis to identify themes related to PRISM. We adapted implementation strategies at each site using these findings. RESULTS: We identified actionable themes within PRISM domains to address during implementation. The most commonly occurring PRISM domains were "organizational characteristics" and "implementation and sustainability infrastructure." Themes included a disconnect between primary care and hospital inpatient teams, concerns about work duplication, and concerns that one nurse could not meet the demand for the program. These themes informed TNP implementation. CONCLUSIONS: The use of PRISM for pre-implementation site assessments yielded important findings that guided adaptations to our implementation approach. Further, barriers and facilitators to TNP implementation may be common to other care coordination interventions. Generating a common language of barriers and facilitators in care coordination initiatives will enhance generalizability and establish best practices. IMPACT STATEMENTS: TNP is a national intensive care coordination program targeting rural Veterans. We operationalized PRISM to guide implementation efforts. We effectively elucidated facilitators, barriers, and unique contextual factors at diverse VHA facilities. The use of PRISM enhances the generalizability of findings across care settings and may optimize implementation of care coordination interventions in the VHA.


Assuntos
Continuidade da Assistência ao Paciente/organização & administração , Implementação de Plano de Saúde/organização & administração , População Rural , Veteranos , Continuidade da Assistência ao Paciente/legislação & jurisprudência , Implementação de Plano de Saúde/legislação & jurisprudência , Humanos , Pesquisa Qualitativa , Estados Unidos , United States Department of Veterans Affairs/legislação & jurisprudência
17.
J Gen Intern Med ; 34(Suppl 1): 67-74, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31098974

RESUMO

BACKGROUND: Transitions of care are high risk for vulnerable populations such as rural Veterans, and adequate care coordination can alleviate many risks. Single-center care coordination programs have shown promise in improving transitional care practices. However, best practices for implementing effective transitional care interventions are unknown, and a common pitfall is lack of understanding of the current process at different sites. The rural Transitions Nurse Program (TNP) is a Veterans Health Administration (VA) intervention that addresses the unique transitional care coordination needs of rural Veterans, and it is currently being implemented in five VA facilities. OBJECTIVE: We sought to employ and study process mapping as a tool for assessing site context prior to implementation of TNP, a new care coordination program. DESIGN AND PARTICIPANTS: Observational qualitative study guided by the Lean Six Sigma approach. Data were collected in January-March 2017 through interviews, direct observations, and group sessions with front-line staff, including VA providers, nurses, and administrative staff from five VA Medical Centers and nine rural Patient-Aligned Care Teams. KEY RESULTS: We integrated key informant interviews, observational data, and group sessions to create ten process maps depicting the care coordination process prior to TNP implementation at each expansion site. These maps were used to adapt implementation through informing the unique role of the Transitions Nurse at each site and will be used in evaluating the program, which is essential to understanding the program's impact. CONCLUSIONS: Process mapping can be a valuable and practical approach to accurately assess site processes before implementation of care coordination programs in complex systems. The process mapping activities were useful in engaging the local staff and simultaneously guided adaptations to the TNP intervention to meet local needs. Our approach-combining multiple data sources while adapting Lean Six Sigma principles into practical use-may be generalizable to other care coordination programs.


Assuntos
Continuidade da Assistência ao Paciente/organização & administração , Implementação de Plano de Saúde/organização & administração , População Rural , Veteranos , Humanos , Pesquisa Qualitativa , Estados Unidos , United States Department of Veterans Affairs/organização & administração
18.
J Gen Intern Med ; 34(Suppl 1): 11-17, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31098966

RESUMO

Delivering well-coordinated care is essential for optimizing clinical outcomes, enhancing patient care experiences, minimizing costs, and increasing provider satisfaction. The Veterans Health Administration (VA) has built a strong foundation for internally coordinating care. However, VA faces mounting internal care coordination challenges due to growth in the number of Veterans using VA care, high complexity in Veterans' care needs, the breadth and depth of VA services, and increasing use of virtual care. VA's Health Services Research and Development service with the Office of Research and Development held a conference assessing the state-of-the-art (SOTA) on care coordination. One workgroup within the SOTA focused on coordination between VA providers for high-need Veterans, including (1) Veterans with multiple chronic conditions; (2) Veterans with high-intensity, focused, specialty care needs; (3) Veterans experiencing care transitions; (4) Veterans with severe mental illness; (5) and Veterans with homelessness and/or substance use disorders. We report on this workgroup's recommendations for policy and organizational initiatives and identify questions for further research. Recommendations from a separate workgroup on coordinating VA and non-VA care are contained in a companion paper. Leaders from research, clinical services, and VA policy will need to partner closely as they develop, implement, assess, and spread effective practices if VA is to fully realize its potential for delivering highly coordinated care to every Veteran.


Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Avaliação das Necessidades , Pesquisa/organização & administração , Congressos como Assunto , Humanos , Estados Unidos , United States Department of Veterans Affairs/organização & administração , Veteranos
19.
Catheter Cardiovasc Interv ; 94(6): 886-892, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31454157

RESUMO

Patients presenting with hemodynamic instability attributable to left ventricular systolic dysfunction and concomitant severe mitral regurgitation (MR) are increasingly recognized and pose complex management challenges. Surgical therapy is typically precluded owing to prohibitive mortality. The role of percutaneous mechanical circulatory support in such cases is well established; however, such interventions may be neither sufficient to achieve optimal stability nor prove definitive. The advent of novel catheter-based mitral repair modalities now offers primary decisive therapeutic intervention. Three cases of cardiogenic shock with severe MR illustrate the salutary hemodynamic and clinical responses to percutaneous mechanical support and valve repair by mitral clip.


Assuntos
Cateterismo Cardíaco , Implante de Prótese de Valva Cardíaca , Coração Auxiliar , Hemodinâmica , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Choque Cardiogênico/terapia , Disfunção Ventricular Esquerda/terapia , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco/instrumentação , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/instrumentação , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Choque Cardiogênico/diagnóstico por imagem , Choque Cardiogênico/fisiopatologia , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia
20.
Nano Lett ; 18(4): 2351-2357, 2018 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-29558623

RESUMO

Transition metal dichalcogenides (TMDs) are particularly sensitive to mechanical strain because they are capable of experiencing high atomic displacements without nucleating defects to release excess energy. Being promising for photonic applications, it has been shown that as certain phases of layered TMDs MX2 (M = Mo or W; X = S, Se, or Te) are scaled to a thickness of one monolayer, the photoluminescence response is dramatically enhanced due to the emergence of a direct electronic band gap compared with their multilayer or bulk counterparts, which typically exhibit indirect band gaps. Recently, mechanical strain has also been predicted to enable direct excitonic recombination in these materials, in which large changes in the photoluminescence response will occur during an indirect-to-direct band gap transition brought on by elastic tensile strain. Here, we demonstrate an enhancement of 2 orders of magnitude in the photoluminescence emission intensity in uniaxially strained single crystalline WSe2 bilayers. Through a theoretical model that includes experimentally relevant system conditions, we determine this amplification to arise from a significant increase in direct excitonic recombination. Adding confidence to the high levels of elastic strain achieved in this report, we observe strain-independent, mode-dependent Grüneisen parameters over the entire range of tensile strain (1-3.59%), which were obtained as 1.149 ± 0.027, 0.307 ± 0.061, and 0.357 ± 0.103 for the E2g, A1g, and A21g optical phonon modes, respectively. These results can inform the predictive strain-engineered design of other atomically thin indirect semiconductors, in which a decrease in out-of-plane bonding strength may lead to an increase in the strength of strain-coupled optoelectronic effects.

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