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1.
Clin Lung Cancer ; 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38553325

RESUMO

INTRODUCTION: Lung cancer survival is improving in the United States. We investigated whether there was a similar trend within the Veterans Health Administration (VHA), the largest integrated healthcare system in the United States. MATERIALS AND METHODS: Data from the Veterans Affairs Central Cancer Registry were analyzed for temporal survival trends using Kaplan-Meier estimates and linear regression. RESULTS: A total number of 54,922 Veterans were identified with lung cancer diagnosed from 2010 to 2017. Histologies were classified as non-small-cell lung cancer (NSCLC) (64.2%), small cell lung cancer (SCLC) (12.9%), and 'other' (22.9%). The proportion with stage I increased from 18.1% to 30.4%, while stage IV decreased from 38.9% to 34.6% (both P < .001). The 3-year overall survival (OS) improved for stage I (58.6% to 68.4%, P < .001), stage II (35.5% to 48.4%, P < .001), stage III (18.7% to 29.4%, P < .001), and stage IV (3.4% to 7.8%, P < .001). For NSCLC, the median OS increased from 12 to 21 months (P < .001), and the 3-year OS increased from 24.1% to 38.3% (P < .001). For SCLC, the median OS remained unchanged (8 to 9 months, P = .10), while the 3-year OS increased from 9.1% to 12.3% (P = .014). Compared to White Veterans, Black Veterans with NSCLC had similar OS (P = .81), and those with SCLC had higher OS (P = .003). CONCLUSION: Lung cancer survival is improving within the VHA. Compared to White Veterans, Black Veterans had similar or higher survival rates. The observed racial equity in outcomes within a geographically and socioeconomically diverse population warrants further investigation to better understand and replicate this achievement in other healthcare systems.

2.
Adv Mater ; : e2310743, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38189562

RESUMO

An integrated design, modeling, and multi-material 3D printing platform for fabricating liquid crystal elastomer (LCE) lattices in both homogeneous and heterogeneous layouts with spatially programmable nematic director order and local composition is reported. Depending on their compositional topology, these lattices exhibit different reversible shape-morphing transformations upon cycling above and below their respective nematic-to-isotropic transition temperatures. Further, it is shown that there is good agreement between their experimentally observed deformation response and model predictions for all LCE lattice designs evaluated. Lastly, an inverse design model is established and the ability to print LCE lattices with the predicted deformation behavior is demonstrated. This work opens new avenues for creating architected LCE lattices that may find potential application in energy-dissipating structures, microfluidic pumping, mechanical logic, and soft robotics.

3.
J Cancer Policy ; 38: 100453, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37977216

RESUMO

INTRODUCTION: Lung cancer is a major cause of death in the United States. Social determinants of health (SDOH) are important factors that impact the treatment and prognosis of lung cancer. The social vulnerability index (SVI) is a validated measure of SDOH. This cross-sectional study aimed to investigate the impact of the SVI on lung cancer mortality using descriptive epidemiology. METHODS: Mortality data for lung malignancies from 2014 to 2018 was obtained from the CDC database and was age-adjusted and standardized to the population in the year 2000. The SVI for the same years was obtained from the CDC Agency for Toxic Substances and Disease Registry database. Age-adjusted mortality rates (AAMR) were estimated for each SVI quartile (SVI-Q) and demographic subgroup. RESULTS: We found that counties in SVI-Q4 (most vulnerable) had a higher cumulative AAMR compared to counties in SVI-Q1 (least vulnerable), accounting for a 4.48 excess death rate per 100,000 person-years. AAMR among males in SVI-Q4 was higher compared to SVI-Q1, accounting for a 9.96 excess death rate per 100,000 person-years, whereas no mortality differences were observed for female populations between SVI-Q4 and SVI-Q1. AAMR in SVI-Q4 was higher for both Hispanic and non-Hispanic populations, except for American Indian/Alaska Native populations. Similar trends were observed in both metropolitan and non-metropolitan counties. CONCLUSION: Our study suggests that the SVI may play a significant role in lung cancer mortality and highlights the need for interventions targeting vulnerable populations to improve outcomes.


Assuntos
Neoplasias Pulmonares , Masculino , Feminino , Humanos , Vulnerabilidade Social , Estudos Transversais , Populações Vulneráveis
4.
J Natl Compr Canc Netw ; 21(10): 1050-1057.e13, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37856197

RESUMO

BACKGROUND: More than 50% of patients with lung cancer are admitted to the hospital while receiving treatment, which is a burden to patients and the healthcare system. This study characterizes the risk factors and outcomes of patients with lung cancer who were admitted to the hospital. METHODS: A multidisciplinary oncology care team conducted a retrospective medical record review of patients with lung cancer admitted in 2018. Demographics, disease and admission characteristics, and end-of-life care utilization were recorded. Following a multidisciplinary consensus review process, admissions were determined to be either "avoidable" or "unavoidable." Generalized estimating equation logistic regression models assessed risks and outcomes associated with avoidable admissions. RESULTS: In all, 319 admissions for 188 patients with a median age of 66 years (IQR, 59-74 years) were included. Cancer-related symptoms accounted for 65% of hospitalizations. Common causes of unavoidable hospitalizations were unexpected disease progression causing symptoms, chronic obstructive pulmonary disease exacerbation, and infection. Of the 47 hospitalizations identified as avoidable (15%), the median overall survival was 1.6 months compared with 9.7 months (hazard ratio, 2.07; 95% CI, 1.34-3.19; P<.001) for unavoidable hospitalizations. Significant reasons for avoidable admissions included cancer-related pain (P=.02), hypervolemia (P=.03), patient desire to initiate hospice services (P=.01), and errors in medication reconciliation or distribution (P<.001). Errors in medication management caused 26% of the avoidable hospitalizations. Of admissions in patients receiving immunotherapy (n=102) or targeted therapy (n=44), 9% were due to adverse effects of treatment. Patients receiving immunotherapy and targeted therapy were at similar risk of avoidable hospitalizations compared with patients not receiving treatment (P=.3 and P=.1, respectively). CONCLUSIONS: We found that 15% of hospitalizations among patients with lung cancer were potentially avoidable. Uncontrolled symptoms, delayed implementation of end-of-life care, and errors in medication reconciliation were associated with avoidable inpatient admissions. Symptom management tools, palliative care integration, and medication reconciliations may mitigate hospitalization risk.


Assuntos
Neoplasias Pulmonares , Humanos , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Estudos Retrospectivos , Hospitalização , Cuidados Paliativos , Hospitais
5.
Front Health Serv ; 3: 1209720, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37674596

RESUMO

Introduction: To assess healthcare professionals' perceptions of rural barriers and facilitators of lung cancer screening program implementation in a Veterans Health Administration (VHA) setting through a series of one-on-one interviews with healthcare team members. Methods: Based on measures developed using Reach Effectiveness Adoption Implementation Maintenance (RE-AIM), we conducted a cross-sectional qualitative study consisting of one-on-one semi-structured telephone interviews with VHA healthcare team members at 10 Veterans Affairs medical centers (VAMCs) between December 2020 and September 2021. An iterative inductive and deductive approach was used for qualitative analysis of interview data, resulting in the development of a conceptual model to depict rural barriers and facilitators of lung cancer screening program implementation. Results: A total of 30 interviews were completed among staff, providers, and lung cancer screening program directors and a conceptual model of rural barriers and facilitators of lung cancer screening program implementation was developed. Major themes were categorized within institutional and patient environments. Within the institutional environment, participants identified systems-level (patient communication, resource availability, workload), provider-level (attitudes and beliefs, knowledge, skills and capabilities), and external (regional and national networks, incentives) barriers to and facilitators of lung cancer screening program implementation. Within the patient environment, participants revealed patient-level (modifiable vulnerabilities) barriers and facilitators as well as ecological modifiers (community) that influence screening behavior. Discussion: Understanding rural barriers to and facilitators of lung cancer screening program implementation as perceived by healthcare team members points to opportunities and approaches for improving lung cancer screening reach, implementation and effectiveness in VHA rural settings.

6.
Biofabrication ; 16(1)2023 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-37734324

RESUMO

Rete ridges consist of undulations between the epidermis and dermis that enhance the mechanical properties and biological function of human skin. However, most human skin models are fabricated with a flat interface between the epidermal and dermal layers. Here, we report a micro-stamping method for producing human skin models patterned with rete ridges of controlled geometry. To mitigate keratinocyte-induced matrix degradation, telocollagen-fibrin matrices with and without crosslinks enable these micropatterned features to persist during longitudinal culture. Our human skin model exhibits an epidermis that includes the following markers: cytokeratin 14, p63, and Ki67 in the basal layer, cytokeratin 10 in the suprabasal layer, and laminin and collagen IV in the basement membrane. We demonstrated that two keratinocyte cell lines, one from a neonatal donor and another from an adult diabetic donor, are compatible with this model. We tested this model using an irritation test and showed that the epidermis prevents rapid penetration of sodium dodecyl sulfate. Gene expression analysis revealed differences in keratinocytes obtained from the two donors as well as between 2D (control) and 3D culture conditions. Our human skin model may find potential application for drug and cosmetic testing, disease and wound healing modeling, and aging studies.


Assuntos
Biomimética , Pele , Adulto , Recém-Nascido , Humanos , Epiderme , Queratinócitos , Derme
7.
Proc Natl Acad Sci U S A ; 120(35): e2305322120, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37603766

RESUMO

T cell bispecific antibodies (TCBs) are the focus of intense development for cancer immunotherapy. Recently, peptide-MHC (major histocompatibility complex)-targeted TCBs have emerged as a new class of biotherapeutics with improved specificity. These TCBs simultaneously bind to target peptides presented by the polymorphic, species-specific MHC encoded by the human leukocyte antigen (HLA) allele present on target cells and to the CD3 coreceptor expressed by human T lymphocytes. Unfortunately, traditional models for assessing their effects on human tissues often lack predictive capability, particularly for "on-target, off-tumor" interactions. Here, we report an immune-infiltrated, kidney organoid-on-chip model in which peripheral blood mononuclear cells (PBMCs) along with nontargeting (control) or targeting TCB-based tool compounds are circulated under flow. The target consists of the RMF peptide derived from the intracellular tumor antigen Wilms' tumor 1 (WT1) presented on HLA-A2 via a bivalent T cell receptor-like binding domain. Using our model, we measured TCB-mediated CD8+ T cell activation and killing of RMF-HLA-A2-presenting cells in the presence of PBMCs and multiple tool compounds. DP47, a non-pMHC-targeting TCB that only binds to CD3 (negative control), does not promote T cell activation and killing. Conversely, the nonspecific ESK1-like TCB (positive control) promotes CD8+ T cell expansion accompanied by dose-dependent T cell-mediated killing of multiple cell types, while WT1-TCB* recognizing the RMF-HLA-A2 complex with high specificity, leads solely to selective killing of WT1-expressing cells within kidney organoids under flow. Our 3D kidney organoid model offers a platform for preclinical testing of cancer immunotherapies and investigating tissue-immune system interactions.


Assuntos
Anticorpos Biespecíficos , Humanos , Antígeno HLA-A2 , Leucócitos Mononucleares , Rim , Organoides
9.
Lab Chip ; 23(14): 3226-3237, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37341452

RESUMO

Modelling proximal tubule physiology and pharmacology is essential to understand tubular biology and guide drug discovery. To date, multiple models have been developed; however, their relevance to human disease has yet to be evaluated. Here, we report a 3D vascularized proximal tubule-on-a-multiplexed chip (3DvasPT-MC) device composed of co-localized cylindrical conduits lined with confluent epithelium and endothelium, embedded within a permeable matrix, and independently addressed by a closed-loop perfusion system. Each multiplexed chip contains six 3DvasPT models. We performed RNA-seq and compared the transcriptomic profile of proximal tubule epithelial cells (PTECs) and human glomerular endothelial cells (HGECs) seeded in our 3D vasPT-MCs and on 2D transwell controls with and without a gelatin-fibrin coating. Our results reveal that the transcriptional profile of PTECs is highly dependent on both the matrix and flow, while HGECs exhibit greater phenotypic plasticity and are affected by the matrix, PTECs, and flow. PTECs grown on non-coated Transwells display an enrichment of inflammatory markers, including TNF-a, IL-6, and CXCL6, resembling damaged tubules. However, this inflammatory response is not observed for 3D proximal tubules, which exhibit expression of kidney signature genes, including drug and solute transporters, akin to native tubular tissue. Likewise, the transcriptome of HGEC vessels resembled that of sc-RNAseq from glomerular endothelium when seeded on this matrix and subjected to flow. Our 3D vascularized tubule on chip model has utility for both renal physiology and pharmacology.


Assuntos
Células Endoteliais , Túbulos Renais Proximais , Humanos , Túbulos Renais Proximais/metabolismo , Epitélio , Rim , Células Epiteliais/metabolismo , Fenótipo
10.
Adv Mater ; 35(33): e2210748, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37163476

RESUMO

Embedded bioprinting enables the rapid design and fabrication of complex tissues that recapitulate in vivo microenvironments. However, few biological matrices enable good print fidelity, while simultaneously facilitate cell viability, proliferation, and migration. Here, a new microporogen-structured (µPOROS) matrix for embedded bioprinting is introduced, in which matrix rheology, printing behavior, and porosity are tailored by adding sacrificial microparticles composed of a gelatin-chitosan complex to a prepolymer collagen solution. To demonstrate its utility, a 3D tumor model is created via embedded printing of a murine melanoma cell ink within the µPOROS collagen matrix at 4 °C. The collagen matrix is subsequently crosslinked around the microparticles upon warming to 21 °C, followed by their melting and removal at 37 °C. This process results in a µPOROS matrix with a fibrillar collagen type-I network akin to that observed in vivo. Printed tumor cells remain viable and proliferate, while antigen-specific cytotoxic T cells incorporated in the matrix migrate to the tumor site, where they induce cell death. The integration of the µPOROS matrix with embedded bioprinting opens new avenues for creating complex tissue microenvironments in vitro that may find widespread use in drug discovery, disease modeling, and tissue engineering for therapeutic use.


Assuntos
Bioimpressão , Neoplasias , Camundongos , Animais , Bioimpressão/métodos , Impressão Tridimensional , Colágeno , Engenharia Tecidual/métodos , Gelatina , Hidrogéis , Tecidos Suporte , Microambiente Tumoral
11.
Am J Prev Med ; 65(5): 901-905, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37169315

RESUMO

INTRODUCTION: Lung cancer screening can save lives through the early detection of lung cancer, and professional societies recommend key lung cancer screening program components to ensure high-quality screening. Yet, little is known about the key components that comprise the various screening program models in routine clinical settings. The objective was to compare the utilization of these key components across centralized, hybrid, and decentralized lung cancer screening programs. METHODS: The survey was designed to identify current structures and processes of lung cancer screening programs. It was administered electronically to Veterans Health Administration facilities nationally (N=122) between August and December 2021. Results were analyzed between March and August 2022 and stratified by self-identified lung cancer screening program type, and we tested the hypothesis that centralized screening programs would be more likely to have implemented practices that support lung cancer screening, followed by hybrid and decentralized programs, using the Cochran-Armitage trend test. RESULTS: Overall, 69 (56.6%) facilities completed the survey, and respondents were lung cancer screening coordinators (39.1%), pulmonologists (33.3%), and oncologists (10.1%). Facilities most frequently self-identified as having a centralized (37.7%) program model, followed by identifying as having hybrid (30.4%) and decentralized (20.3%) programs. There was varying implementation of practices to support lung cancer screening, with hybrid and decentralized programs less likely to have lung cancer screening registries, lung cancer screening steering committees, or dedicated lung cancer screening coordinators. CONCLUSIONS: Although there is overlap between the components of various lung cancer screening program types, centralized programs more frequently implemented practices before the initial screening to support lung cancer screening. This work provides a path for future investigations to identify which lung cancer screening practices are effective to improve lung cancer screening outcomes, which could help inform implementation in settings with limited resources.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Saúde dos Veteranos , Detecção Precoce de Câncer/métodos , Inquéritos e Questionários
12.
Am J Prev Med ; 65(5): 844-853, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37224985

RESUMO

INTRODUCTION: Lung cancer screening is widely underutilized. Organizational factors, such as readiness for change and belief in the value of change (change valence), may contribute to underutilization. The aim of this study was to evaluate the association between healthcare organizations' preparedness and lung cancer screening utilization. METHODS: Investigators cross-sectionally surveyed clinicians, staff, and leaders at10 Veterans Affairs from November 2018 to February 2021 to assess organizational readiness to implement change. In 2022, investigators used simple and multivariable linear regression to evaluate the associations between facility-level organizational readiness to implement change and change valence with lung cancer screening utilization. Organizational readiness to implement change and change valence were calculated from individual surveys. The primary outcome was the proportion of eligible Veterans screened using low-dose computed tomography. Secondary analyses assessed scores by healthcare role. RESULTS: The overall response rate was 27.4% (n=1,049), with 956 complete surveys analyzed: median age of 49 years, 70.3% female, 67.6% White, 34.6% clinicians, 61.1% staff, and 4.3% leaders. For each 1-point increase in median organizational readiness to implement change and change valence, there was an associated 8.4-percentage point (95% CI=0.2, 16.6) and a 6.3-percentage point increase in utilization (95% CI= -3.9, 16.5), respectively. Higher clinician and staff median scores were associated with increased utilization, whereas leader scores were associated with decreased utilization after adjusting for other roles. CONCLUSIONS: Healthcare organizations with higher readiness and change valence utilized more lung cancer screening. These results are hypothesis generating. Future interventions to increase organizations' preparedness, especially among clinicians and staff, may increase lung cancer screening utilization.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Inovação Organizacional , Neoplasias Pulmonares/diagnóstico , Atenção à Saúde , Modelos Lineares
13.
Sci Transl Med ; 15(690): eadd9779, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-37018418

RESUMO

Implantable tubes, shunts, and other medical conduits are crucial for treating a wide range of conditions from ears and eyes to brain and liver but often impose serious risks of device infection, obstruction, migration, unreliable function, and tissue damage. Efforts to alleviate these complications remain at an impasse because of fundamentally conflicting design requirements: Millimeter-scale size is required to minimize invasiveness but exacerbates occlusion and malfunction. Here, we present a rational design strategy that reconciles these trade-offs in an implantable tube that is even smaller than the current standard of care. Using tympanostomy tubes (ear tubes) as an exemplary case, we developed an iterative screening algorithm and show how unique curved lumen geometries of the liquid-infused conduit can be designed to co-optimize drug delivery, effusion drainage, water resistance, and biocontamination/ingrowth prevention in a single subcapillary-length-scale device. Through extensive in vitro studies, we demonstrate that the engineered tubes enabled selective uni- and bidirectional fluid transport; nearly eliminated adhesion and growth of common pathogenic bacteria, blood, and cells; and prevented tissue ingrowth. The engineered tubes also enabled complete eardrum healing and hearing preservation and exhibited more efficient and rapid antibiotic delivery to the middle ear in healthy chinchillas compared with current tympanostomy tubes, without resulting in ototoxicity at up to 24 weeks. The design principle and optimization algorithm presented here may enable tubes to be customized for a wide range of patient needs.


Assuntos
Otite Média com Derrame , Humanos , Otite Média com Derrame/diagnóstico , Ventilação da Orelha Média/métodos , Orelha Média/patologia , Próteses e Implantes , Antibacterianos
14.
J Am Coll Radiol ; 20(3): 314-323, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36922105

RESUMO

PURPOSE: The aim of this study was to gather the perspectives of Black women on breast cancer risk assessment through a series of one-on-one interviews. METHODS: The authors conducted a cross-sectional qualitative study consisting of one-on-one semistructured telephone interviews with Black women in Tennessee between September 2020 and November 2020. Guided by the Health Belief Model, qualitative analysis of interview data was performed in an iterative inductive and deductive approach and resulted in the development of a conceptual framework to depict influences on a woman's decision to engage with breast cancer risk assessment. RESULTS: A total of 37 interviews were completed, and a framework of influences on a woman's decision to engage in breast cancer risk assessment was developed. Study participants identified several emerging themes regarding women's perspectives on breast cancer risk assessment and potential influences on women's decisions to engage with risk assessment. Much of women's decision context was based on risk appraisal (perceived severity of cancer and susceptibility of cancer), emotions (fear and trust), and perceived risks and benefits of having risk assessment. The decision was further influenced by modifiers such as communication, the risk assessment protocol, access to health care, knowledge, and health status. Perceived challenges to follow-up if identified as high risk also influenced women's decisions to pursue risk assessment. CONCLUSIONS: Black women in this study identified several barriers to engagement with breast cancer risk assessment. Efforts to overcome these barriers and increase the use of breast cancer risk assessment can potentially serve as a catalyst to address existing breast cancer disparities. Continued work is needed to develop patient-centric strategies to overcome identified barriers.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Estudos Transversais , Medição de Risco , Emoções , Tomada de Decisões , Pesquisa Qualitativa
15.
J Am Coll Radiol ; 20(3): 342-351, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36922108

RESUMO

PURPOSE: To assess health care professionals' perceptions of barriers to the utilization of breast cancer risk assessment tools in the public health setting through a series of one-on-one interviews with health care team members. METHODS: We conducted a cross-sectional qualitative study consisting of one-on-one semistructured telephone interviews with health care team members in the public health setting in the state of Tennessee between May 2020 and October 2020. An iterative inductive-deductive approach was used for qualitative analysis of interview data, resulting in the development of a conceptual framework to depict influences of provider behavior in the utilization of breast cancer risk assessment. RESULTS: A total of 24 interviews were completed, and a framework of influences of provider behavior in the utilization of breast cancer risk assessment was developed. Participants identified barriers to the utilization of breast cancer risk assessment (knowledge and understanding of risk assessment tools, workflow challenges, and availability of personnel); patient-level barriers as perceived by health care team members (psychological, economic, educational, and environmental); and strategies to increase the utilization of breast cancer risk assessment at the provider level (leadership buy-in, training, supportive policies, and incentives) and patient level (improved communication and better understanding of patients' perceived cancer risk and severity of cancer). CONCLUSIONS: Understanding barriers to implementation of breast cancer risk assessment and strategies to overcome these barriers as perceived by health care team members offers an opportunity to improve implementation of risk assessment and to identify a racially, geographically, and socioeconomically diverse population of young women at high risk for breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Estudos Transversais , Motivação , Medição de Risco , Equipe de Assistência ao Paciente , Pesquisa Qualitativa , Pessoal de Saúde
16.
Am J Physiol Cell Physiol ; 324(3): C757-C768, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36745528

RESUMO

Kidney organoids cultured on adherent matrices in the presence of superfusate flow generate vascular networks and exhibit more mature podocyte and tubular compartments compared with static controls (Homan KA, Gupta N, Kroll KT, Kolesky DB, Skylar-Scott M, Miyoshi T, Mau D, Valerius MT, Ferrante T, Bonventre JV, Lewis JA, Morizane R. Nat Methods 16: 255-262, 2019; Takasato M, Er PX, Chiu HS, Maier B, Baillie GJ, Ferguson C, Parton RG, Wolvetang EJ, Roost MS, Chuva de Sousa Lopes SM, Little MH. Nature 526: 564-568, 2015.). However, their physiological function has yet to be systematically investigated. Here, we measured mechano-induced changes in intracellular Ca2+ concentration ([Ca2+]i) in tubules isolated from organoids cultured for 21-64 days, microperfused in vitro or affixed to the base of a specimen chamber, and loaded with fura-2 to measure [Ca2+]i. A rapid >2.5-fold increase in [Ca2+]i from a baseline of 195.0 ± 22.1 nM (n = 9; P ≤ 0.001) was observed when microperfused tubules from organoids >40 days in culture were subjected to luminal flow. In contrast, no response was detected in tubules isolated from organoids <30 days in culture. Nonperfused tubules (41 days) subjected to a 10-fold increase in bath flow rate also exhibited a threefold increase in [Ca2+]i from baseline (P < 0.001). Mechanosensitive PIEZO1 channels contribute to the flow-induced [Ca2+]i response in mouse distal tubule (Carrisoza-Gaytan R, Dalghi MG, Apodaca GL, Kleyman TR, Satlin LM. The FASEB J 33: 824.25, 2019.). Immunodetectable apical and basolateral PIEZO1 was identified in tubular structures by 21 days in culture. Basolateral PIEZO1 appeared to be functional as basolateral exposure of nonperfused tubules to the PIEZO1 activator Yoda 1 increased [Ca2+]i (P ≤ 0.001) in segments from organoids cultured for >30 days, with peak [Ca2+]i increasing with advancing days in culture. These results are consistent with a maturational increase in number and/or activity of flow/stretch-sensitive Ca2+ channels, including PIEZO1, in tubules of static organoids in culture.


Assuntos
Sinalização do Cálcio , Cálcio , Túbulos Renais , Animais , Camundongos , Cálcio/metabolismo , Fura-2 , Canais Iônicos/metabolismo , Rim/metabolismo , Túbulos Renais/metabolismo
17.
Adv Mater ; 35(15): e2209270, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36658462

RESUMO

Light- and ink-based 3D printing methods have vastly expanded the design space and geometric complexity of architected ceramics. However, light-based methods are typically confined to a relatively narrow range of preceramic and particle-laden resins, while ink-based methods are limited in geometric complexity due to layerwise assembly. Here, embedded 3D printing is combined with microwave-activated curing to generate architected ceramics with spatially controlled composition in freeform shapes. Aqueous colloidal inks are printed within a support matrix, rapidly cured via microwave-activated polymerization, and subsequently dried and sintered into dense architectures composed of one or more oxide materials. This integrated manufacturing method opens new avenues for the design and fabrication of complex ceramic architectures with programmed composition, density, and form for myriad applications.

18.
Implement Sci Commun ; 4(1): 5, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635719

RESUMO

BACKGROUND: Lung cancer screening is a complex clinical process that includes identification of eligible individuals, shared decision-making, tobacco cessation, and management of screening results. Adaptations to the delivery process for lung cancer screening in situ are understudied and underreported, with the potential loss of important considerations for improved implementation. The Framework for Reporting Adaptations and Modifications-Expanded (FRAME) allows for a systematic enumeration of adaptations to implementation of evidence-based practices. We applied FRAME to study adaptations in lung cancer screening delivery processes implemented by lung cancer screening programs in a Veterans Health Administration (VHA) Enterprise-Wide Initiative. METHODS: We prospectively conducted semi-structured interviews at baseline and 1-year intervals with lung cancer screening program navigators at 10 Veterans Affairs Medical Centers (VAMCs) between 2019 and 2021. Using this data, we developed baseline (1st) process maps for each program. In subsequent years (year 1 and year 2), each program navigator reviewed the process maps. Adaptations in screening processes were identified, documented, and mapped to FRAME categories. RESULTS: We conducted a total of 16 interviews across 10 VHA lung cancer screening programs (n=6 in year 1, n=10 in year 2) to collect adaptations. In year 1 (2020), six programs were operational and eligible. Of these, three reported adaptations to their screening process that were planned or in response to COVID-19. In year 2 (2021), all 10 programs were operational and eligible. Programs reported 14 adaptations in year 2. These adaptations were planned and unplanned and often triggered by increased workload; 57% of year 2 adaptations were related to the identification and eligibility of Veterans and 43% were related to follow-up with Veterans for screening results. Throughout the 2 years, adaptations related to data management and patient tracking occurred in 60% of programs to improve the data collection and tracking of Veterans in the screening process. CONCLUSIONS: Using FRAME, we found that adaptations occurred primarily in the areas of patient identification and communication of results due to increased workload. These findings highlight navigator time and resource considerations for sustainability and scalability of existing and future lung cancer screening programs as well as potential areas for future intervention.

19.
Nature ; 613(7945): 682-688, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36653452

RESUMO

Helical structures are ubiquitous in nature and impart unique mechanical properties and multifunctionality1. So far, synthetic architectures that mimic these natural systems have been fabricated by winding, twisting and braiding of individual filaments1-7, microfluidics8,9, self-shaping1,10-13 and printing methods14-17. However, those fabrication methods are unable to simultaneously create and pattern multimaterial, helically architected filaments with subvoxel control in arbitrary two-dimensional (2D) and three-dimensional (3D) motifs from a broad range of materials. Towards this goal, both multimaterial18-23 and rotational24 3D printing of architected filaments have recently been reported; however, the integration of these two capabilities has yet to be realized. Here we report a rotational multimaterial 3D printing (RM-3DP) platform that enables subvoxel control over the local orientation of azimuthally heterogeneous architected filaments. By continuously rotating a multimaterial nozzle with a controlled ratio of angular-to-translational velocity, we have created helical filaments with programmable helix angle, layer thickness and interfacial area between several materials within a given cylindrical voxel. Using this integrated method, we have fabricated functional artificial muscles composed of helical dielectric elastomer actuators with high fidelity and individually addressable conductive helical channels embedded within a dielectric elastomer matrix. We have also fabricated hierarchical lattices comprising architected helical struts containing stiff springs within a compliant matrix. Our additive-manufacturing platform opens new avenues to generating multifunctional architected matter in bioinspired motifs.


Assuntos
Órgãos Artificiais , Materiais Biomiméticos , Biomimética , Elastômeros/química , Condutividade Elétrica , Impressão Tridimensional , Biomimética/métodos , Materiais Biomiméticos/química , Rotação , Músculos/química
20.
Child Care Health Dev ; 49(4): 760-768, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36513964

RESUMO

AIM: The aim of this study is to describe the individualized occupational performance issues identified by parents/carers and children prior to selective dorsal rhizotomy (SDR) surgery and analyse change up to 2 years post surgery in goal attainment and quality of life (QoL). METHOD: The Australian SDR Research Registry (trial registration: ACTRN12618000985280) was used to extract data for individualized goals, goal attainment and QoL based on the Canadian Occupational Performance Measure (COPM) and the Cerebral Palsy Quality of Life Questionnaire for Children (CP QOL-Child parent-proxy) at baseline and 1 and 2 years following SDR. Change in mean scores was analysed using linear mixed models. RESULTS: Fifty-two children had COPM scores at baseline and 1 and/or 2 years post, of which 28 had two QoL scores. COPM problem areas included leisure (n = 39), productivity (n = 37) and self-care (n = 173). The most common goals were walking (26.1%), participation in physical activities (17.7%) and transitions (14.1%). Mean COPM scores improved significantly between baseline to 1 year and baseline to 2 years (P < 0.001). Mean QoL scores improved between baseline to 1 year for functional QoL domains: participation and physical health (P = 0.003) and pain and impact of disability (P = 0.011). CONCLUSIONS: Collaborative goal setting is an integral part of family-centred rehabilitation practice. The COPM was an appropriate individualized outcome measure in identifying meaningful goals for our SDR cohort. Results demonstrate improved scores in goal attainment and improvement in functional QoL domains. This paper highlights the need to include outcomes that measure daily life experiences.


Assuntos
Paralisia Cerebral , Rizotomia , Humanos , Rizotomia/métodos , Qualidade de Vida , Objetivos , Austrália , Canadá , Paralisia Cerebral/reabilitação , Resultado do Tratamento
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