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1.
Am J Emerg Med ; 80: 227.e7-227.e11, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38702221

RESUMEN

The tricuspid regurgitation pressure gradient (TRPG) reflects the difference in pressure between the right ventricle and right atrium (ΔPRV-RA). Its estimation by echocardiography correlates well with that obtained using right-heart catheterization. An elevated TRPG is an important marker for identifying right ventricular dysfunction in both the acute and chronic settings. However, in the "wide-open" variant of TR, the TRPG counterintuitively falls. Failure to recognize this potential pitfall and underlying pathophysiology can cause underestimation of the severity of right ventricular dysfunction. This could lead to erroneous fluid tolerance assessments, and potentially harmful resuscitative and airway management strategies. In this manuscript, we illustrate the pathophysiology and potential pitfall of wide-open TR through a series of cases in which emergency physicians made the diagnosis using cardiac point-of-care ultrasound. To our knowledge, this clinical series is the first to demonstrate recognition of the paradoxically-low TRPG of wide-open TR, which guided appropriate management of critically ill patients in the emergency department.


Asunto(s)
Ecocardiografía , Servicio de Urgencia en Hospital , Insuficiencia de la Válvula Tricúspide , Disfunción Ventricular Derecha , Humanos , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagen , Insuficiencia de la Válvula Tricúspide/fisiopatología , Insuficiencia de la Válvula Tricúspide/complicaciones , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/fisiopatología , Ecocardiografía/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Sistemas de Atención de Punto , Adulto
2.
Pharmacoepidemiol Drug Saf ; 31(9): 944-952, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35689299

RESUMEN

With availability of voluminous sets of observational data, an empirical paradigm to screen for drug repurposing opportunities (i.e., beneficial effects of drugs on nonindicated outcomes) is feasible. In this article, we use a linked claims and electronic health record database to comprehensively explore repurposing effects of antihypertensive drugs. We follow a target trial emulation framework for causal inference to emulate randomized controlled trials estimating confounding adjusted effects of antihypertensives on each of 262 outcomes of interest. We then fit hierarchical models to the results as a form of postprocessing to account for multiple comparisons and to sift through the results in a principled way. Our motivation is twofold. We seek both to surface genuinely intriguing drug repurposing opportunities and to elucidate through a real application some study design decisions and potential biases that arise in this context.


Asunto(s)
Antihipertensivos , Reposicionamiento de Medicamentos , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Causalidad , Bases de Datos Factuales , Registros Electrónicos de Salud , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
3.
Opt Express ; 27(10): 14457-14471, 2019 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-31163895

RESUMEN

Quantifying collagen fiber architecture has clinical and scientific relevance across a variety of tissue types and adds functionality to otherwise largely qualitative imaging modalities. Optical coherence tomography (OCT) is uniquely suited for this task due to its ability to capture the collagen microstructure over larger fields of view than traditional microscopy. Existing image processing techniques for quantifying fiber architecture, while accurate and effective, are very slow for processing large datasets and tend to lack structural specificity. We describe here a computationally efficient method for quantifying and visualizing collagen fiber organization. The algorithm is demonstrated on swine atria, bovine anterior cruciate ligament, and human cervical tissue samples. Additionally, we show an improved performance for images with crimped fiber textures and low signal to noise when compared to similar methods.

4.
Connect Tissue Res ; 58(5): 393-406, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27599801

RESUMEN

Osteoarthritis (OA) is a degenerative joint condition characterized by painful cartilage lesions that impair joint mobility. Current treatments such as lavage, microfracture, and osteochondral implantation fail to integrate newly formed tissue with host tissues and establish a stable transition to subchondral bone. Similarly, tissue-engineered grafts that facilitate cartilage and bone regeneration are challenged by how to integrate the graft seamlessly with surrounding host cartilage and/or bone. This review centers on current approaches to promote cartilage graft integration. It begins with an overview of articular cartilage structure and function, as well as degenerative changes to this relationship attributed to aging, disease, and trauma. A discussion of the current progress in integrative cartilage repair follows, focusing on graft or scaffold design strategies targeting cartilage-cartilage and/or cartilage-bone integration. It is emphasized that integrative repair is required to ensure long-term success of the cartilage graft and preserve the integrity of the newly engineered articular cartilage. Studies involving the use of enzymes, choice of cell source, biomaterial selection, growth factor incorporation, and stratified versus gradient scaffolds are therefore highlighted. Moreover, models that accurately evaluate the ability of cartilage grafts to enhance tissue integrity and prevent ectopic calcification are also discussed. A summary and future directions section concludes the review.


Asunto(s)
Cartílago Articular , Osteoartritis , Ingeniería de Tejidos , Envejecimiento/metabolismo , Envejecimiento/patología , Animales , Cartílago Articular/metabolismo , Cartílago Articular/patología , Cartílago Articular/cirugía , Humanos , Osteoartritis/metabolismo , Osteoartritis/patología , Osteoartritis/cirugía , Heridas y Lesiones/metabolismo , Heridas y Lesiones/patología , Heridas y Lesiones/cirugía
5.
Connect Tissue Res ; 57(6): 476-487, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27599920

RESUMEN

Currently, the mechanism governing the regeneration of the soft tissue-to-bone interface, such as the transition between the anterior cruciate ligament (ACL) and bone, is not known. Focusing on the ACL-to-bone insertion, this study tests the novel hypothesis that interactions between cells from the ligament (fibroblasts) and bone (osteoblasts) initiate interface regeneration. Specifically, these heterotypic cell interactions direct the fibrochondrogenic differentiation of interface-relevant cell populations, defined here as ligament fibroblasts and bone marrow stromal cells (BMSC). The objective of this study is to examine the effects of heterotypic cellular interactions on BMSC or fibroblast growth and biosynthesis, as well as expression of fibrocartilage-relevant markers in tri-culture. The effects of cell-cell physical contact and paracrine interactions between fibroblasts and osteoblasts were also determined. It was found that, in tri-culture with fibroblasts and osteoblasts, BMSC exhibited greater fibrochondrogenic potential than ligament fibroblasts. The growth of BMSC decreased while proteoglycan production and TGF-ß3 expression increased. Moreover, tri-culture regulated BMSC response via paracrine factors, and interestingly, fibroblast-osteoblast contact further promoted proteoglycan and TGF-ß1 synthesis as well as induced SOX9 expression in BMSC. Collectively, the findings of this study suggest that fibroblast-osteoblast interactions play an important role in regulating the stem cell niche for fibrocartilage regeneration, and the mechanisms of these interactions are directed by paracrine factors and augmented with direct cell-cell contact.


Asunto(s)
Comunicación Celular , Técnicas de Cultivo de Célula/métodos , Diferenciación Celular , Células Madre Mesenquimatosas/citología , Fosfatasa Alcalina/metabolismo , Animales , Biomarcadores/metabolismo , Bovinos , Proliferación Celular , Supervivencia Celular , Fibroblastos/citología , Fibroblastos/metabolismo , Glicosaminoglicanos/metabolismo , Osteoblastos/citología , Osteoblastos/metabolismo , Comunicación Paracrina , Factor de Transcripción SOX9/metabolismo
6.
Methods ; 84: 99-102, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25846397

RESUMEN

A significant challenge to orthopaedic soft tissue repair is the biological fixation of autologous or allogeneic grafts with bone, whereby the lack of functional integration between such grafts and host bone has limited the clinical success of anterior cruciate ligament (ACL) and other common soft tissue-based reconstructive grafts. The inability of current surgical reconstruction to restore the native fibrocartilaginous insertion between the ACL and the femur or tibia, which minimizes stress concentration and facilitates load transfer between the soft and hard tissues, compromises the long-term clinical functionality of these grafts. To enable integration, a stratified scaffold design that mimics the multiple tissue regions of the ACL interface (ligament-fibrocartilage-bone) represents a promising strategy for composite tissue formation. Moreover, distinct cellular organization and phase-specific matrix heterogeneity achieved through co- or tri-culture within the scaffold system can promote biomimetic multi-tissue regeneration. Here, we describe the methods for fabricating a tri-phasic scaffold intended for ligament-bone integration, as well as the tri-culture of fibroblasts, chondrocytes, and osteoblasts on the stratified scaffold for the formation of structurally contiguous and compositionally distinct regions of ligament, fibrocartilage and bone. The primary advantage of the tri-phasic scaffold is the recapitulation of the multi-tissue organization across the native interface through the layered design. Moreover, in addition to ease of fabrication, each scaffold phase is similar in polymer composition and therefore can be joined together by sintering, enabling the seamless integration of each region and avoiding delamination between scaffold layers.


Asunto(s)
Ingeniería de Tejidos/métodos , Andamios del Tejido , Animales , Ligamento Cruzado Anterior/citología , Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior , Bovinos , Técnicas de Cultivo de Célula , Condrocitos/citología , Fibroblastos/citología , Humanos , Oseointegración , Osteoblastos/citología
7.
Knee Surg Sports Traumatol Arthrosc ; 24(7): 2365-73, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25466277

RESUMEN

PURPOSE: The purpose of this study was to summarize the recent developments in the field of tissue engineering as they relate to multilayer scaffold designs in musculoskeletal regeneration. METHODS: Clinical and basic research studies that highlight the current knowledge and potential future applications of the multilayer scaffolds in orthopaedic tissue engineering were evaluated and the best evidence collected. Studies were divided into three main categories based on tissue types and interfaces for which multilayer scaffolds were used to regenerate: bone, osteochondral junction and tendon-to-bone interfaces. RESULTS: In vitro and in vivo studies indicate that the use of stratified scaffolds composed of multiple layers with distinct compositions for regeneration of distinct tissue types within the same scaffold and anatomic location is feasible. This emerging tissue engineering approach has potential applications in regeneration of bone defects, osteochondral lesions and tendon-to-bone interfaces with successful basic research findings that encourage clinical applications. CONCLUSIONS: Present data supporting the advantages of the use of multilayer scaffolds as an emerging strategy in musculoskeletal tissue engineering are promising, however, still limited. Positive impacts of the use of next generation scaffolds in orthopaedic tissue engineering can be expected in terms of decreasing the invasiveness of current grafting techniques used for reconstruction of bone and osteochondral defects, and tendon-to-bone interfaces in near future.


Asunto(s)
Huesos , Cartílago , Tendones , Andamios del Tejido , Humanos , Ortopedia , Regeneración , Ingeniería de Tejidos/métodos
8.
J Immunol ; 191(12): 6165-77, 2013 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-24244024

RESUMEN

TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1ß, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl(-/-)Mertk(-/-) double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.


Asunto(s)
Giro Dentado/patología , Microglía/fisiología , Neurogénesis/fisiología , Proteínas Proto-Oncogénicas/fisiología , Proteínas Tirosina Quinasas Receptoras/fisiología , Animales , Astrocitos/metabolismo , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Citocinas/biosíntesis , Citocinas/genética , Replicación del ADN , Encefalitis/inmunología , Encefalitis/patología , Regulación de la Expresión Génica , Indometacina/farmacología , Interleucina-6/antagonistas & inhibidores , Interleucina-6/deficiencia , Interleucina-6/genética , Interleucina-6/fisiología , Lipopolisacáridos/toxicidad , Sistema de Señalización de MAP Quinasas , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/inmunología , FN-kappa B/metabolismo , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , Neurogénesis/genética , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Óxido Nítrico Sintasa de Tipo II/genética , Proteínas Proto-Oncogénicas/deficiencia , Proteínas Proto-Oncogénicas/genética , Proteínas Tirosina Quinasas Receptoras/deficiencia , Proteínas Tirosina Quinasas Receptoras/genética , Receptores Toll-Like/inmunología , Tirosina Quinasa c-Mer , Tirosina Quinasa del Receptor Axl
9.
Annu Rev Biomed Eng ; 15: 201-26, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23642244

RESUMEN

Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge. This review begins with a description of the developmental processes and the resultant structure-function relationships that translate into the functional grading necessary for stress transfer between soft tissue and bone. It then discusses the interface healing response, with a focus on the influence of mechanical loading and the role of cell-cell interactions. The review continues with a description of current efforts in interface tissue engineering, highlighting key strategies for the regeneration of the soft tissue-to-bone interface, and concludes with a summary of challenges and future directions.


Asunto(s)
Desarrollo Óseo/fisiología , Huesos/patología , Ingeniería de Tejidos/métodos , Animales , Materiales Biocompatibles/química , Comunicación Celular , Humanos , Ligamentos/patología , Regeneración , Medicina Regenerativa/métodos , Estrés Mecánico , Tendones/patología , Cicatrización de Heridas
10.
medRxiv ; 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38260276

RESUMEN

Background: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the only bnAb HIV prevention efficacy studies to date, the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. Greater efficacy is required before passively administered bnAbs become a viable option for HIV prevention; furthermore subcutaneous (SC) or intramuscular (IM) administration may be preferred. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. Methods: Participants were recruited between 02 February 2018 and 09 October 2018. 124 healthy participants without HIV were randomized to receive five VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), SC (T4: 2.5 mg/kg, T5: 5 mg/kg) or IM (T6: 2.5 mg/kg or P6: placebo) routes at four-month intervals. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA after the first dose through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum pharmacokinetics. Neutralization activity was measured in a TZM-bl assay and anti-drug antibodies (ADA) were assayed using a tiered bridging assay testing strategy. Results: Injections were well-tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusions were generally well-tolerated, with infusion reactions reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals) following the first administration were 29.0 µg/mL (25.2, 33.4), 58.5 µg/mL (49.4, 69.3), and 257.2 µg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 µg/mL (8.8, 13.3) and 22.8 µg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 µg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM concentrations immediately prior to the second administration were 3.4 µg/mL (2.5, 4.6), 6.5 µg/mL (5.6, 7.5), and 27.2 µg/mL (23.9, 31.0) with IV dosing; 0.97 µg/mL (0.65, 1.4) and 3.1 µg/mL (2.2, 4.3) with SC dosing, and 2.6 µg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titres, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titre ADA at a lone timepoint. VRC07-523LS has an estimated mean half-life of 42 days (95% CI: 40.5, 43.5), approximately twice as long as VRC01. Conclusions: VRC07-523LS was safe and well-tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens.

11.
Optom Vis Sci ; 90(5): 439-47, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23538436

RESUMEN

PURPOSE: To investigate relationships between changes to corneal and ocular aberrations induced by orthokeratology (OK) and their influence on visual function. METHODS: Eighteen subjects (aged 20 to 23 years) were fitted with OK lenses (BE Enterprises Pty Ltd, Australia), manufactured in Boston XO material (Bausch & Lomb Boston, Wilmington, MA), and worn overnight for seven nights. Corneal and ocular aberrations were simultaneously captured (Discovery, Innovative Visual Systems, Elmhurst, IL), and contrast sensitivity function was measured on days 1 and 7, within 2 and 8 hours after lens removal on waking. Data from the eye achieving the higher myopic correction were analyzed for changes over time. RESULTS: There was a significant refractive effect at all visits. Orthokeratology induced an increase in corneal and ocular root mean square higher order aberrations (HOAs) and a positive shift in spherical aberration (SA) on day 1, with further increases by day 7. Increases in root mean square coma became significant by day 7. Changes to corneal and ocular SA were similar on day 1; however, by day 7, there was a greater increase in corneal than ocular SA, indicating a change in internal SA. Orthokeratology led to an overall decrease in contrast sensitivity function, which was isolated to spatial frequency changes on day 1 at 1 cycle per degree and on day 7 at 1 and 8 cycles per degree. CONCLUSIONS: A greater positive shift in corneal compared with ocular SA on day 7 suggests a negative shift in internal SA, which would be consistent with an increased accommodative response. Lack of any difference on day 1 indicates that this may be an ocular adaptation response toward neutralizing induced positive SA, rather than a direct effect of SA changes on the accommodation mechanism.


Asunto(s)
Lentes de Contacto , Córnea/patología , Miopía/fisiopatología , Miopía/terapia , Procedimientos de Ortoqueratología/métodos , Refracción Ocular , Córnea/fisiopatología , Topografía de la Córnea , Femenino , Estudios de Seguimiento , Humanos , Masculino , Miopía/patología , Resultado del Tratamiento , Adulto Joven
12.
Cogn Sci ; 47(9): e13344, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37718476

RESUMEN

Many events that humans and other species experience contain regularities in which certain elements within an event predict certain others. While some of these regularities involve tracking the co-occurrences between temporally adjacent stimuli, others involve tracking the co-occurrences between temporally distant stimuli (i.e., nonadjacent dependencies, NADs). Prior research shows robust learning of adjacent dependencies in humans and other species, whereas learning NADs is more difficult, and often requires support from properties of the stimulus to help learners notice the NADs. Here, we report on seven experiments that examined NAD learning from various types of visual stimuli, exploring the effects of dynamic motion on adults' NAD learning from visual sequences involving human and nonhuman agents. We tested adults' NAD learning from visual sequences of human actions, object transformations, static images of human postures, and static images of an object in different postures. We found that dynamic motion aids the acquisition of NADs. We also found that learning NADs in sequences involving human agents is more robust compared to sequences involving nonhuman objects. We propose that dynamic motion and human agents both independently result in richer representations that provide a stronger signal for NAD learning.


Asunto(s)
NAD , Aprendizaje Espacial , Adulto , Humanos , Dapsona , Movimiento (Física)
13.
POCUS J ; 8(1): 38-42, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37152343

RESUMEN

Bladder rupture is an uncommon injury that leads to significant morbidity and mortality. Though occurring mostly due to trauma, this life-threatening pathology may also occur spontaneously or after a procedure such as transurethral resection of bladder tumor (TURBT). Computed tomography (CT) cystography is the standard imaging modality for diagnosis. However, this test is unlikely to be ordered in a patient with undifferentiated abdominal pain unless there is specific suspicion for this diagnosis. In our emergency department, a 48 year-old male with history of bladder cancer and TURBT two weeks prior to arrival presented with severe abdominal pain and difficulty urinating for 3 days. Point of care ultrasound (POCUS) revealed an irregularly shaped bladder, likely site of bladder rupture, and large amount of abdominal free fluid with sediment. These findings prompted an expedited diagnostic CT scan with cystography. Emergent exploratory laparotomy ultimately confirmed a small bladder defect with 2.5 L of urinary ascites. The diagnosis of non-traumatic bladder rupture can be overlooked in patients presenting with a peritonitic abdominen. The typically ordered test for such patients is standard CT, which carries a high false-negative rate for bladder rupture. This case highlights the utility of POCUS in facilitating a rapid diagnosis.

14.
J Shoulder Elbow Surg ; 21(2): 266-77, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22244070

RESUMEN

Rotator cuff tears represent the most common shoulder injuries in the United States. The debilitating effect of this degenerative condition coupled with the high incidence of failure associated with existing graft choices underscores the clinical need for alternative grafting solutions. The 2 critical design criteria for the ideal tendon graft would require the graft to not only exhibit physiologically relevant mechanical properties but also be able to facilitate functional graft integration by promoting the regeneration of the native tendon-to-bone interface. Centered on these design goals, this review will highlight current approaches to functional and integrative tendon repair. In particular, the application of biomimetic design principles through the use of nanofiber- and nanocomposite-based scaffolds for tendon tissue engineering will be discussed. This review will begin with nanofiber-based approaches to functional tendon repair, followed by a section highlighting the exciting research on tendon-to-bone interface regeneration, with an emphasis on implementation of strategic biomimicry in nanofiber scaffold design and the concomitant formation of graded multi-tissue systems for integrative soft-tissue repair. This review will conclude with a summary and discussion of future directions.


Asunto(s)
Biomimética/métodos , Procedimientos Ortopédicos/métodos , Manguito de los Rotadores/cirugía , Traumatismos de los Tendones/cirugía , Andamios del Tejido , Humanos , Nanofibras/uso terapéutico , Diseño de Prótesis , Regeneración/fisiología , Lesiones del Manguito de los Rotadores , Resistencia a la Tracción , Cicatrización de Heridas/fisiología
15.
Front Bioeng Biotechnol ; 10: 925838, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36312546

RESUMEN

Connective tissue extracellular matrix (ECM) consists of an interwoven network of contiguous collagen fibers that regulate cell activity, direct biological function, and guide tissue homeostasis throughout life. Recently, ECM analogs have emerged as a unique ex vivo culture platform for studying healthy and diseased tissues and in the latter, enabling the screening for and development of therapeutic regimen. Since these tissue models can mitigate the concern that observations from animal models do not always translate clinically, the design and production of a collagenous ECM analogue with relevant chemistry and nano- to micro-scale architecture remains a frontier challenge in the field. Therefore, the objectives of this study are two-fold- first, to apply green electrospinning approaches to the fabrication of an ECM analog with nanoscale mimicry and second, to systematically optimize collagen crosslinking in order to produce a stable, collagen-like substrate with continuous fibrous architecture that supports human cell culture and phenotypic expression. Specifically, the "green" electrospinning solvent acetic acid was evaluated for biofabrication of gelatin-based meshes, followed by the optimization of glutaraldehyde (GTA) crosslinking under controlled ambient conditions. These efforts led to the production of a collagen-like mesh with nano- and micro-scale cues, fibrous continuity with little batch-to-batch variability, and proven stability in both dry and wet conditions. Moreover, the as-fabricated mesh architecture and native chemistry were preserved with augmented mechanical properties. These meshes supported the in vitro expansion of stem cells and the production of a mineralized matrix by human osteoblast-like cells. Collectively these findings demonstrate the potential of green fabrication in the production of a collagen-like ECM analog with physiological relevance. Future studies will explore the potential of this high-fidelity platform for elucidating cell-matrix interactions and their relevance in connective tissue healing.

16.
NPJ Digit Med ; 5(1): 12, 2022 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-35087180

RESUMEN

Current clinical note-taking approaches cannot capture the entirety of information available from patient encounters and detract from patient-clinician interactions. By surveying healthcare providers' current note-taking practices and attitudes toward new clinical technologies, we developed a patient-centered paradigm for clinical note-taking that makes use of hybrid tablet/keyboard devices and artificial intelligence (AI) technologies. PhenoPad is an intelligent clinical note-taking interface that captures free-form notes and standard phenotypic information via a variety of modalities, including speech and natural language processing techniques, handwriting recognition, and more. The output is unobtrusively presented on mobile devices to clinicians for real-time validation and can be automatically transformed into digital formats that would be compatible with integration into electronic health record systems. Semi-structured interviews and trials in clinical settings rendered positive feedback from both clinicians and patients, demonstrating that AI-enabled clinical note-taking under our design improves ease and breadth of information captured during clinical visits without compromising patient-clinician interactions. We open source a proof-of-concept implementation that can lay the foundation for broader clinical use cases.

17.
Orthop Traumatol Surg Res ; 108(4): 103157, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34856404

RESUMEN

BACKGROUND: The purpose of this study was to search for changes in functional outcomes of patients undergoing hip arthroscopy for femoroacetabular impingement (FAI) between short and medium-term follow-up. Secondary aims included reporting rates of revision surgery and total hip arthroplasty (THA) at medium-term follow-up. HYPOTHESIS: We hypothesised that patients' functional outcomes would improve between short and medium-term follow-up. PATIENTS AND METHODS: Consecutive patients undergoing hip arthroscopy with a diagnosis of femoroacetabular impingement with labral tears between February 2013 and June 2015 were included. Twelve item international hip outcome tool (iHOT-12) and EuroQol 5D-5L (EQ-5D) scores were collected preoperatively, at short-term and medium-term follow-up. Short-term scores were recorded at a minimum of one year postoperatively and medium-term scores at a minimum of five years postoperatively. Survivorship was assessed with Kaplan-Meier analysis. RESULTS: Short-term outcome data (at median follow-up 1.6 year, Interquartile range [IQR] 1-2.5) was available for 70 of 87 patients (80.5%) and medium-term outcome data (at median follow-up of 6.5 years, IQR 6-7.1) was available for 68 patients (78.2%). Median age at the time of surgery was 31 years (IQR 25-37). The median iHOT-12 scores at short and medium-term follow-up were 72 (IQR 48.75-91.25) and 85.8 (IQR 66.7-96.7) respectively (p<0.001). Medium-term survivorship was 91.2%. Survivorship following labral repair was 94.2%, and 81.3% following labral debridement (p=0.09). DISCUSSION: Patients undergoing hip arthroscopy for FAI reported continued improvement in iHOT-12 scores between short and medium-term follow-up. Medium-term survivorship following FAI surgery may be greater when the labrum is repaired, although comparisons are limited by their differing indications. Conversion to THA was low with just 4 patients (4.6%) undergoing or being listed for THA at final follow-up. LEVEL OF EVIDENCE: IV, Case series.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Pinzamiento Femoroacetabular , Artroscopía , Pinzamiento Femoroacetabular/diagnóstico , Pinzamiento Femoroacetabular/cirugía , Estudios de Seguimiento , Articulación de la Cadera/cirugía , Humanos , Reoperación , Resultado del Tratamiento
18.
PLoS One ; 17(8): e0267766, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35939422

RESUMEN

BACKGROUND: Widespread use of at-home rapid COVID-19 antigen tests has been proposed as an important public health intervention to interrupt chains of transmission. Antigen tests may be preferred over PCR because they provide on-demand results for relatively low cost and can identify people when they are most likely to be infectious, particularly when used daily. Yet the extent to which a frequent antigen testing intervention will result in a positive public health impact for COVID-19 will depend on high acceptability and high adherence to such regimens. METHODS: We conducted a mixed-methods study assessing acceptability of and adherence to a daily at-home mobile-app connected rapid antigen testing regimen among employees of a US-based media company. Acceptability was assessed across seven domains of the Theoretical Framework of Acceptability. RESULTS: Among 31 study participants, acceptability of the daily testing intervention was generally high, with participants reporting high perceived effectiveness, intervention coherence, and self-efficacy; positive affective attitude; acceptable degree of burden and opportunity cost; and assessing the intervention as ethical. 71% reported a preference to test daily using an at-home antigen test than weekly employment-based PCR. Mean adherence to the 21-day testing regimen was 88% with 43% of participants achieving 100% adherence, 48% testing at least every other day, and 10% testing less than every other day. CONCLUSIONS: Despite overall high acceptability and adherence, we identified three implementation challenges that must be addressed for frequent serial testing for COVID-19 to be implemented at scale and have a positive public health impact. First, users need guidance on how and when to adapt testing frequencies to different epidemiological conditions. Second, users and institutions need guidelines for how to safely store and share test results. Third, implementation of serial testing strategies must prioritize health equity and protect those most vulnerable to COVID-19.


Asunto(s)
COVID-19 , Aplicaciones Móviles , COVID-19/diagnóstico , COVID-19/epidemiología , Prueba de COVID-19 , Atención a la Salud , Humanos , Pandemias
19.
J Occup Environ Med ; 64(9): 742-747, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35121692

RESUMEN

OBJECTIVE: E-waste is rising globally. This is a follow up to our study reporting metals/polybrominated diphenyl ethers (PBDE's)/polychlorinated biphenyls (PCBs) in female e-waste recyclers. Here we report polybrominated, polychlorinated dioxins/furans, and dioxin-like polychlorinated biphenyls in these same workers. METHODS: Female Vietnamese recyclers and non-recyclers recruited; blood samples collected. Polybrominated, polychlorinated dioxins/furans, and dioxin-like polychlorinated biphenyls levels compared in recyclers, non-recyclers, and National Health and Nutrition Examination Surveys (NHANES). RESULTS: Recyclers >non-recyclers: 12378-PBDD, 2378-TBDF, 12378-PCDF, 123478-HxCDF, 123678-HxCDF, 1234678-HpCDF, PCB-126. Non-recyclers >NHANES: 123478-HxCDF, 123678-HxCDF, 234678- HxCDF, PCB-126, PCB-169. NHANES >non-recyclers: 12378-PCDD, 123478-HxCDD, 123678-HxCDD, 123789-HxCDD, 1234678-HpCDD, 123789-HxCDF, 1234678-HpCDF, 1234789-HpCDF, OCDF, PCB-81, PCB-114, PCB-156, PCB-157, PCB-167, PCB-189. Recyclers >NHANES: S: 2378-TeCDF, 12378-PCDF, 23478-PCDF, 123478-HxCDF, 123678- HxCDF, 234678-HxCDF, PCB-126. NHANES >recyclers: 12378-PCDD, 123478-HxCDD, 123678-HxCDD, 123789-HxCDD, 1234678-HpCDD, OCDD, 123789-HxCDF, 1234678-HpCDF, 1234789-HpCDF, OCDF, PCB- 81, PCB-114, PCB-156, PCB-157, PCB-189. CONCLUSION: 12378 PCDD, 2378-TCDD, PCB 126 makeup most total dioxin equivalences (TEQs) in AQ5 these workers, indicating increased exposure; remediation indicated.


Asunto(s)
Benzofuranos , Dioxinas , Residuos Electrónicos , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Pueblo Asiatico , Benzofuranos/análisis , Monitoreo Biológico , Dioxinas/análisis , Femenino , Furanos , Humanos , Encuestas Nutricionales
20.
Env Sci Adv ; 1(3): 276-284, 2022 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-35979328

RESUMEN

The synthesis and bottom-up assembly of nanocellulose by microbes offers unique advantages to tune and meet key design criteria-rapid renewability, low toxicity, scalability, performance, and degradability-for multi-functional, circular economy textiles. However, development of green processing methods that meet these criteria remains a major research challenge. Here, we harness microbial biofabrication of nanocellulose and draw inspiration from ancient textile techniques to engineer sustainable biotextiles with a circular life cycle. The unique molecular self-organization of microbial nanocellulose (MC) combined with bio-phosphorylation with a lecithin treatment yields a compostable material with superior mechanical and flame-retardant properties. Specifically, treatment of MC with a lecithin-phosphocholine emulsion makes sites available to modulate cellulose cross-linking through hydroxyl, phosphate and methylene groups, increasing the interaction between cellulose chains. The resultant bioleather exhibits enhanced tensile strength and high ductility. Bio-phosphorylation with lecithin also redirects the combustion pathway from levoglucosan production towards the formation of foaming char as an insulating oxygen barrier, for outstanding flame retardance. Controlled color modulation is demonstrated with natural dyes. Life cycle impact assessment reveals that MC bioleather has up to an order of magnitude lower carbon footprint than conventional textiles, and a thousandfold reduction in the carcinogenic impact of leather production. Eliminating the use of hazardous substances, these high performance materials disrupt linear production models and strategically eliminate its toxicity and negative climate impacts, with widespread application in fashion, interiors and construction. Importantly, the biotextile approach developed in this study demonstrates the potential of biofabrication coupled with green chemistry for a circular materials economy.

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