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BACKGROUND: Care partners of people with serious illness experience significant challenges and unmet needs during the patient's treatment period and after their death. Learning from others with shared experiences can be valuable, but opportunities are not consistently available. OBJECTIVE: This study aims to design and prototype a regional, facilitated, and web-based peer support network to help active and bereaved care partners of persons with serious illness be better prepared to cope with the surprises that arise during serious illness and in bereavement. METHODS: An 18-member co-design team included active care partners and those in bereavement, people who had experienced serious illness, regional health care and support partners, and clinicians. It was guided by facilitators and peer network subject-matter experts. We conducted design exercises to identify the functions and specifications of a peer support network. Co-design members independently prioritized network specifications, which were incorporated into an early iteration of the web-based network. RESULTS: The team prioritized two functions: (1) connecting care partners to information and (2) facilitating emotional support. The design process generated 24 potential network specifications to support these functions. The highest priorities included providing a supportive and respectful community; connecting people to trusted resources; reducing barriers to asking for help; and providing frequently asked questions and responses. The network platform had to be simple and intuitive, provide technical support for users, protect member privacy, provide publicly available information and a private discussion forum, and be easily accessible. It was feasible to enroll members in the ConnectShareCare web-based network over a 3-month period. CONCLUSIONS: A co-design process supported the identification of critical features of a peer support network for care partners of people with serious illnesses in a rural setting, as well as initial testing and use. Further testing is underway to assess the long-term viability and impact of the network.
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Internet , Grupo Paritario , Apoyo Social , Humanos , Cuidadores/psicología , Enfermedad Crítica/psicologíaRESUMEN
BACKGROUND: Shared decision making (SDM) in breast cancer care improves outcomes, but it is not routinely implemented. Results from the What Matters Most trial demonstrated that early-stage breast cancer surgery conversation aids, when used by surgeons after brief training, improved SDM and patient-reported outcomes. Trial surgeons and patients both encouraged using the conversation aids in routine care. We will develop and evaluate an online learning collaborative, called the SHared decision making Adoption Implementation Resource (SHAIR) Collaborative, to promote early-stage breast cancer surgery SDM by implementing the conversation aids into routine preoperative care. Learning collaboratives are known to be effective for quality improvement in clinical care, but no breast cancer learning collaborative currently exists. Our specific aims are to (1) provide the SHAIR Collaborative resources to clinical sites to use with eligible patients, (2) examine the relationship between the use of the SHAIR Collaborative resources and patient reach, and (3) promote the emergence of a sustained learning collaborative in this clinical field, building on a partnership with the American Society of Breast Surgeons (ASBrS). METHODS: We will conduct a two-phased implementation project: phase 1 pilot at five sites and phase 2 scale up at up to an additional 32 clinical sites across North America. The SHAIR Collaborative online platform will offer free access to conversation aids, training videos, electronic health record and patient portal integration guidance, a feedback dashboard, webinars, support center, and forum. We will use RE-AIM for data collection and evaluation. Our primary outcome is patient reach. Secondary data will include (1) patient-reported data from an optional, anonymous online survey, (2) number of active sites and interviews with site champions, (3) Normalization MeAsure Development questionnaire data from phase 1 sites, adaptations data utilizing the Framework for Reporting Adaptations and Modifications-Extended/-Implementation Strategies, and tracking implementation facilitating factors, and (4) progress on sustainability strategy and plans with ASBrS. DISCUSSION: The SHAIR Collaborative will reach early-stage breast cancer patients across North America, evaluate patient-reported outcomes, engage up to 37 active sites, and potentially inform engagement factors affecting implementation success and may be sustained by ASBrS.
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The relative source contribution (RSC) term has long been used by the US Environmental Protection Agency (USEPA) and state regulatory agencies in setting criteria in water. The RSC reflects the proportion of the total daily intake of a chemical that can be derived from water when all other sources of exposure (e.g., food, air) are considered. This term is applied by the USEPA and state regulatory agencies when deriving ambient water quality criteria, maximum contaminant level goals, and drinking water health advisories for noncarcinogenic and threshold carcinogenic compounds. The value assigned to the RSC term affects the calculated criteria directly, with the allowable concentration in water decreasing with a decreasing RSC. A default RSC value of 20%-applied by regulatory entities in the USA for more than 40 years-assumes that 80% of an individual's exposure to a chemical's reference dose is from nonwater sources. Although the RSC is a chemical-specific parameter, there are few instances where a value other than the default of 20% has been approved and used. In 2000, USEPA outlined the process for developing chemical-specific RSC values, yet primary use of the default RSC value has continued since then. This article reviews USEPA's methodology for deriving chemical-specific RSC values and provides a case example using perfluorooctanoic acid (PFOA) to explore how the USEPA and state regulatory agencies are applying USEPA's guidance. The case study highlights inconsistent derivation of the RSC term, rooted in limitations in the current methodology. We suggest additional clarification of and more thoughtful use of the available data that may not meet USEPA's current adequacy requirements. We also recommend that the USEPA discuss recommendations for using biomonitoring data to set RSCs. Integr Environ Assess Manag 2023;19:605-612. © 2022 SETAC.
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Agua Potable , Fluorocarburos , Contaminantes Químicos del Agua , Agua Potable/análisis , Calidad del Agua , Caprilatos/análisis , Fluorocarburos/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
BACKGROUND: Conversation aids can facilitate shared decision-making and improve patient-centered outcomes. However, few examples exist of sustained use of conversation aids in routine care due to numerous barriers at clinical and organizational levels. We explored factors that will promote the sustained use of two early-stage breast cancer conversation aids. We examined differences in opinions between the two conversation aids and across socioeconomic strata. METHODS: We nested this study within a randomized controlled trial that demonstrated the effectiveness of two early-stage breast cancer surgery conversation aids, one text-based and one picture-based. These conversation aids facilitated more shared decision-making and improved the decision process, among other outcomes, across four health systems with socioeconomically diverse patient populations. We conducted semi-structured interviews with a purposive sample of patient participants across conversation aid assignment and socioeconomic status (SES) and collected observations and field notes. We interviewed trial surgeons and other stakeholders. Two independent coders conducted framework analysis using the NOrmalization MeAsure Development through Normalization Process Theory. We also conducted an inductive analysis. We conducted additional sub-analyses based on conversation aid assignment and patient SES. RESULTS: We conducted 73 semi-structured interviews with 43 patients, 16 surgeons, and 14 stakeholders like nurses, cancer center directors, and electronic health record (EHR) experts. Patients and surgeons felt the conversation aids should be used in breast cancer care in the future and were open to various methods of giving and receiving the conversation aid (EHR, email, patient portal, before consultation). Patients of higher SES were more likely to note the conversation aids influenced their treatment discussion, while patients of lower SES noted more influence on their decision-making. Intervention surgeons reported using the conversation aids did not lengthen their typical consultation time. Most intervention surgeons felt using the conversation aids enhanced their usual care after using it a few times, and most patients felt it appeared part of their normal routine. CONCLUSIONS: Key factors that will guide the future sustained implementation of the conversation aids include adapting to existing clinical workflows, flexibility of use, patient characteristics, and communication preferences. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03136367 , registered on May 2, 2017.
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Neoplasias de la Mama , Neoplasias de la Mama/terapia , Comunicación , Toma de Decisiones , Toma de Decisiones Conjunta , Técnicas de Apoyo para la Decisión , Femenino , Humanos , Participación del PacienteRESUMEN
BACKGROUND: Women of lower socioeconomic status (SES) with early-stage breast cancer are more likely to report poorer physician-patient communication, lower satisfaction with surgery, lower involvement in decision making, and higher decision regret compared to women of higher SES. The objective of this study was to understand how to support women across socioeconomic strata in making breast cancer surgery choices. METHODS: We conducted a 3-arm (Option Grid, Picture Option Grid, and usual care), multisite, randomized controlled superiority trial with surgeon-level randomization. The Option Grid (text only) and Picture Option Grid (pictures plus text) conversation aids were evidence-based summaries of available breast cancer surgery options on paper. Decision quality (primary outcome), treatment choice, treatment intention, shared decision making (SDM), anxiety, quality of life, decision regret, and coordination of care were measured from T0 (pre-consultation) to T5 (1-year after surgery. RESULTS: Sixteen surgeons saw 571 of 622 consented patients. Patients in the Picture Option Grid arm (n = 248) had higher knowledge (immediately after the visit [T2] and 1 week after surgery or within 2 weeks of the first postoperative visit [T3]), an improved decision process (T2 and T3), lower decision regret (T3), and more SDM (observed and self-reported) compared to usual care (n = 257). Patients in the Option Grid arm (n = 66) had higher decision process scores (T2 and T3), better coordination of care (12 weeks after surgery or within 2 weeks of the second postoperative visit [T4]), and more observed SDM (during the surgical visit [T1]) compared to usual care arm. Subgroup analyses suggested that the Picture Option Grid had more impact among women of lower SES and health literacy. Neither intervention affected concordance, treatment choice, or anxiety. CONCLUSIONS: Paper-based conversation aids improved key outcomes over usual care. The Picture Option Grid had more impact among disadvantaged patients. LAY SUMMARY: The objective of this study was to understand how to help women with lower incomes or less formal education to make breast cancer surgery choices. Compared with usual care, a conversation aid with pictures and text led to higher knowledge. It improved the decision process and shared decision making (SDM) and lowered decision regret. A text-only conversation aid led to an improved decision process, more coordinated care, and higher SDM compared to usual care. The conversation aid with pictures was more helpful for women with lower income or less formal education. Conversation aids with pictures and text helped women make better breast cancer surgery choices.
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Neoplasias de la Mama/cirugía , Toma de Decisiones Conjunta , Adulto , Anciano , Comunicación , Técnicas de Apoyo para la Decisión , Femenino , Humanos , Persona de Mediana Edad , Participación del Paciente , Clase SocialRESUMEN
Academic medical centers rarely require all of their research faculty and staff to participate in educational programs on the responsible conduct of research (RCR). There is also little published evidence of RCR programs addressing high-profile, internal cases of misconduct as a way of promoting deliberation and learning. In the wake of major research misconduct, Duke University School of Medicine (DUSoM) expanded its RCR education activities to include all DUSoM faculty and staff engaged in research. The program included formal deliberation of the Translational Omics misconduct case, which occurred at Duke. Over 5,000 DUSoM faculty and staff participated in the first phase of this new program, with a 100% completion rate. The article reports on the program's development, challenges and successes, and future directions. This experience at Duke University illustrates that, although challenging and resource intensive, engagement with RCR activities can be integrated into programs for all research faculty and staff. Formal, participatory deliberation of recent cases of internal misconduct can add a novel dimension of reflection and openness to RCR educational activities.
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Curriculum , Facultades de Medicina , Mala Conducta Científica , North Carolina , Desarrollo de ProgramaRESUMEN
Introduction. Breast cancer is the second most common malignancy in women. The Decision Quality Instrument (DQI) measures the extent to which patients are informed and involved in breast surgery decisions and receive treatment that aligns with their preferences. There are limited data on the performance of the DQI in women of lower socioeconomic status (SES). Our aims were to 1) examine (and if necessary adapt) the readability, usability, and acceptability of the DQI and 2) explore whether it captures factors important to breast cancer surgery decisions among women of lower SES (relevance). Methods. We conducted semistructured cognitive interviews with women of lower SES (based on insurance status, income, and education) who had completed early-stage breast cancer treatments at three cancer centers. We used a two-step thematic analysis with dual independent coding. The study team (including Patient Partners and a Community Advisory Board) reviewed and refined suggested changes. The revised DQI was presented in two focus groups of breast cancer survivors. Results. We conducted 39 interviews. Participants found most parts of the DQI to be helpful and easy to understand. We made the following suggested changes: 1) added a glossary of key terms, 2) added two answer choices and an open text question in the goals and concerns subscale, 3) reworded the treatment intention question, and 4) revised the knowledge subscale instructions since several women disliked the wording and were unsure of what was expected. Discussion. The readability, usability, acceptability, and relevance of a measure that was primarily developed and validated in women of higher SES required adaptation for optimal use by women of lower SES. Further research will test these adaptations in lower SES populations.
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BACKGROUND: Breast cancer is the most commonly diagnosed malignancy in women. Mastectomy and breast-conserving surgery (BCS) have equivalent survival for early stage breast cancer. However, each surgery has different benefits and harms that women may value differently. Women of lower socioeconomic status (SES) diagnosed with early stage breast cancer are more likely to experience poorer doctor-patient communication, lower satisfaction with surgery and decision-making, and higher decision regret compared to women of higher SES. They often play a more passive role in decision-making and are less likely to undergo BCS. Our aim is to understand how best to support women of lower SES in making decisions about early stage breast cancer treatments and to reduce disparities in decision quality across socioeconomic strata. METHODS: We will conduct a three-arm, multi-site randomized controlled superiority trial with stratification by SES and clinician-level randomization. At four large cancer centers in the United States, 1100 patients (half higher SES and half lower SES) will be randomized to: (1) Option Grid, (2) Picture Option Grid, or (3) usual care. Interviews, field-notes, and observations will be used to explore strategies that promote the interventions' sustained use and dissemination. Community-Based Participatory Research will be used throughout. We will include women aged at least 18 years of age with a confirmed diagnosis of early stage breast cancer (I to IIIA) from both higher and lower SES, provided they speak English, Spanish, or Mandarin Chinese. Our primary outcome measure is the 16-item validated Decision Quality Instrument. We will use a regression framework, mediation analyses, and multiple informants analysis. Heterogeneity of treatment effects analyses for SES, age, ethnicity, race, literacy, language, and study site will be performed. DISCUSSION: Currently, women of lower SES are more likely to make treatment decisions based on incomplete or uninformed preferences, potentially leading to poorer decision quality, quality of life, and decision regret. This study hopes to identify solutions that effectively improve patient-centered care across socioeconomic strata and reduce disparities in decision and care quality. TRIAL REGISTRATION: NCT03136367 at ClinicalTrials.gov Protocol version: Manuscript based on study protocol version 2.2, 7 November 2017.
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Neoplasias de la Mama/cirugía , Técnicas de Apoyo para la Decisión , Disparidades en Atención de Salud , Relaciones Médico-Paciente , Clase Social , Adulto , Neoplasias de la Mama/patología , Protocolos Clínicos , Comunicación , Toma de Decisiones , Emociones , Femenino , Humanos , Estadificación de Neoplasias , Satisfacción del Paciente , Medición de RiesgoRESUMEN
Alpha-hexachlorocyclohexane (alpha-HCH) is one of eight structural isomers that have been used worldwide as insecticides. Although no longer produced or used agriculturally in the United States, exposure to HCH isomers is of continuing concern due to legacy usage and persistence in the environment. The U.S. Environmental Protection Agency (EPA) classifies alpha-HCH as a probable human carcinogen and provides a slope factor of 6.3 (mg/kg-day)(-1) for the compound, based on hepatic nodules and hepatocellular carcinomas observed in male mice and derived using a default linear approach for modeling carcinogens. EPA's evaluation, last updated in 1993, does not consider more recently available guidance that allows for the incorporation of mode of action (MOA) for determining a compound's dose-response. Contrary to the linear approach assumed by EPA, the available data indicate that alpha-HCH exhibits carcinogenicity via an MOA that yields a nonlinear, threshold dose-response. In our analysis, we conducted an MOA evaluation and dose-response analysis for alpha-HCH-induced liver carcinogenesis. We concluded that alpha-HCH causes liver tumors in rats and mice through an MOA involving increased promotion of cell growth, or mitogenesis. Based on these findings, we developed a threshold, cancer-based, reference dose (RfD) for alpha-HCH.
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Pruebas de Carcinogenicidad , Carcinoma Hepatocelular/inducido químicamente , Transformación Celular Neoplásica/inducido químicamente , Hexaclorociclohexano/toxicidad , Insecticidas/toxicidad , Neoplasias Hepáticas/inducido químicamente , Hígado/efectos de los fármacos , Animales , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Transformación Celular Neoplásica/patología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Modelos Lineales , Hígado/patología , Neoplasias Hepáticas/patología , Masculino , Ratones , Modelos Biológicos , Nivel sin Efectos Adversos Observados , Dinámicas no Lineales , Ratas , Medición de Riesgo , Factores Sexuales , Especificidad de la Especie , Factores de TiempoRESUMEN
Federal and other regulatory agencies often use or claim to use a weight of evidence (WoE) approach in chemical evaluation. Their approaches to the use of WoE, however, differ significantly, rely heavily on subjective professional judgment, and merit improvement. We review uses of WoE approaches in key articles in the peer-reviewed scientific literature, and find significant variations. We find that a hypothesis-based WoE approach, developed by Lorenz Rhomberg et al., can provide a stronger scientific basis for chemical assessment while improving transparency and preserving the appropriate scope of professional judgment. Their approach, while still evolving, relies on the explicit specification of the hypothesized basis for using the information at hand to infer the ability of an agent to cause human health impacts or, more broadly, affect other endpoints of concern. We describe and endorse such a hypothesis-based WoE approach to chemical evaluation.
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Scientists, activists, industry, and governments have raised concerns about health and environmental risks of nanoscale materials. The Society for Risk Analysis convened experts in September 2008 in Washington, DC to deliberate on issues relating to the unique attributes of nanoscale materials that raise novel concerns about health risks. This article reports on the overall themes and findings of the workshop, uncovering the underlying issues for each of these topics that become recurring themes. The attributes of nanoscale particles and other nanomaterials that present novel issues for risk analysis are evaluated in a risk analysis framework, identifying challenges and opportunities for risk analysts and others seeking to assess and manage the risks from emerging nanoscale materials and nanotechnologies. Workshop deliberations and recommendations for advancing the risk analysis and management of nanotechnologies are presented.
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Nanotecnología , Gestión de Riesgos , Exposición a Riesgos Ambientales , Tamaño de la PartículaRESUMEN
During the past decade, advances have been made in the identification, development, and application of alcohol biomarkers. This is important because of the unique functions that alcohol biomarkers can serve in various applied settings. To carry out these functions, biomarkers must display several features including validity, reliability, adequacy of temporal window of assessment, reasonable cost, and transportability. During the past two decades, several traditional alcohol biomarkers have been studied in multiple human studies. Meanwhile, several new, promising biomarkers, including various alcohol metabolites and alcohol biosensors, are being explored in human studies. In addition, researchers have explored using biomarkers in combination and using biomarkers in combination with self-reports, resulting in increased sensitivity with little sacrifice in specificity. Despite these advances, more research is needed to validate biomarkers, especially the new ones, in humans. Moreover, recent advances in high-throughput technologies for genomics, proteomics, and metabolomics offer unique opportunities to discover novel biomarkers, while additional research is needed to perfect newly developed alcohol sensors. Development of more accurate biomarkers will help practicing clinicians to more effectively screen and monitor individuals who suffer from alcohol use disorders.
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Consumo de Bebidas Alcohólicas/metabolismo , Trastornos Relacionados con Alcohol/metabolismo , Biomarcadores/metabolismo , Investigación Biomédica/tendencias , Trastornos Relacionados con Alcohol/diagnóstico , Derecho Penal , Humanos , Atención Primaria de Salud , Psicometría , Centros de Tratamiento de Abuso de Sustancias , Lugar de TrabajoRESUMEN
OBJECTIVES: Taxanes have reported response rates of 20% to 40% in recurrent ovarian cancer (ROC) but are less well studied as a later-line treatment. We reviewed our experience with taxanes in ROC to determine (1) if a taxane-free interval is associated with response rates in women with ROC and (2) if the use of intervening therapy (IT) affects subsequent response rates to taxanes. METHODS: We retrospectively identified women who received first- or second-line platinum-taxane therapy and later received a single-agent taxane. Demographics, intervening regimens, and follow-up and survival data were collected. Responses were characterized by cancer antigen 125 levels based on the Gynecologic Cancer InterGroup serologic response definitions. RESULTS: We identified 46 women who met the eligibility criteria. The median age was 57 years (range, 39-78 years). The median interval between taxanes was 25.8 months (range, 2.9-85.5 months), with 10 (21%) of the women were treated 12 months or less from their last taxane and 37 (79%) treated more than 12 months. The median number of IT was 2 (range, 0-5). Forty patients (87%) received paclitaxel; 6 (13%) received docetaxel. All patients treated 12 months or less from their last taxane responded (P = 0.02). The number of IT was associated with a better response; all women (100%) treated who had no IT, 7 (54%) of 13 women with 1 to 2 ITs, and 7 (39%) of 18 women with 3 ITs or more responded. The overall survival was 13.4 months in responders versus 10.6 months in nonresponders (P = 0.27). CONCLUSIONS: Taxanes maintain an activity as a later-line agent, even with 3 or more intervening therapies. However, the highest responses were seen if taxanes were used within 12 months of the last platinum-based combination. The lack of an increased response with aprolonged taxane-free interval is likely related to the number of IT, consistent with the emergence of multidrug resistance.
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Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Taxoides/uso terapéutico , Adulto , Anciano , Carcinoma Papilar/tratamiento farmacológico , Carcinoma Papilar/metabolismo , Carcinoma Papilar/secundario , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/secundario , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/secundario , Neoplasias de las Trompas Uterinas/metabolismo , Neoplasias de las Trompas Uterinas/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Peritoneales/metabolismo , Neoplasias Peritoneales/patología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Environmental factors likely contribute to the etiology of many progressive neurologic diseases. Such factors include putative neurotoxins that are often byproducts of commercial industries, potentially exposing corporations to liabilities when their products or activities are linked to the development of disease. Any hint of scientific data that support such a cause and effect relationship often encourages plaintiffs' attorneys to file suits against corporations alleging harm to their clients forcing corporations and employers to defend themselves. Both plaintiff and defendant teams hire expert witnesses who are frequently active investigators in relevant fields to bolster their positions. These legal proceedings can influence investigators and hamper research. Interactions with researchers can lead to personal financial or career gain that may bias research findings or impugn other investigators. Even researchers who have not been retained by either side of a legal dispute may be forced to respond to subpoenas for research data causing a substantial loss of research time for investigators and financial burdens on universities. Courts may require release of research records containing personal health information that could sully the trust research participants have in investigators. Litigation and its peripheral effects may bias investigators, impede research efforts, and harm research participants, thereby undermining efforts to understand the cause of neurologic disease.
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Investigación Biomédica/ética , Investigación Biomédica/legislación & jurisprudencia , Testimonio de Experto/legislación & jurisprudencia , Responsabilidad Legal , Neurología/ética , Neurología/legislación & jurisprudencia , Revelación de la Verdad , Testimonio de Experto/ética , Humanos , Estados UnidosRESUMEN
The function of adhesion receptors in both cell adhesion and migration depends critically on interactions with the cytoskeleton. During cell adhesion, cytoskeletal interactions stabilize receptors to strengthen adhesive contacts. In contrast, during cell migration, adhesion proteins are believed to interact with dynamic components of the cytoskeleton, permitting the transmission of traction forces through the receptor to the extracellular environment. The L1 cell adhesion molecule (L1CAM), a member of the Ig superfamily, plays a crucial role in both the migration of neuronal growth cones and the static adhesion between neighboring axons. To understand the basis of L1CAM function in adhesion and migration, we quantified directly the diffusion characteristics of L1CAM on the upper surface of ND-7 neuroblastoma hybrid cells as an indication of receptor-cytoskeleton interactions. We find that cell surface L1CAM engages in diffusion, retrograde movement, and stationary behavior, consistent with interactions between L1CAM and two populations of cytoskeleton proteins. We provide evidence that the cytoskeletal adaptor protein ankyrin mediates stationary behavior while inhibiting the actin-dependent retrograde movement of L1CAM. Moreover, inhibitors of L1CAM-ankyrin interactions promote L1CAM-mediated axon growth. Together, these results suggest that ankyrin binding plays a crucial role in the anti-coordinate regulation of L1CAM-mediated adhesion and migration.