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1.
Proc Natl Acad Sci U S A ; 119(12): e2116870119, 2022 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-35302889

RESUMEN

SignificanceRecent political events show that members of extreme political groups support partisan violence, and survey evidence supposedly shows widespread public support. We show, however, that, after accounting for survey-based measurement error, support for partisan violence is far more limited. Prior estimates overstate support for political violence because of random responding by disengaged respondents and because of a reliance on hypothetical questions about violence in general instead of questions on specific acts of political violence. These same issues also cause the magnitude of the relationship between previously identified correlates and partisan violence to be overstated. As policy makers consider interventions designed to dampen support for violence, our results provide critical information about the magnitude of the problem.


Asunto(s)
Política , Violencia , Encuestas y Cuestionarios , Estados Unidos
2.
Phys Rev Lett ; 131(22): 220803, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38101374

RESUMEN

Dynamical decoupling techniques constitute an integral part of many quantum sensing platforms, often leading to orders-of-magnitude improvements in coherence time and sensitivity. Most ac sensing sequences involve a periodic echolike structure, in which the target signal is synchronized with the echo period. We show that for strongly interacting systems, this construction leads to a fundamental sensitivity limit associated with imperfect interaction decoupling. We present a simple physical picture demonstrating the origin of this limitation, and further formalize these considerations in terms of concise higher-order decoupling rules. We then show how these limitations can be surpassed by identifying a novel sequence building block, in which the signal period matches twice the echo period. Using these decoupling rules and the resulting sequence building block, we experimentally demonstrate significant improvements in dynamical decoupling timescales and magnetic field sensitivity, opening the door for new applications in quantum sensing and quantum many-body physics.

3.
Phys Rev Lett ; 130(21): 210403, 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37295118

RESUMEN

Understanding the microscopic mechanisms of thermalization in closed quantum systems is among the key challenges in modern quantum many-body physics. We demonstrate a method to probe local thermalization in a large-scale many-body system by exploiting its inherent disorder and use this to uncover the thermalization mechanisms in a three-dimensional, dipolar-interacting spin system with tunable interactions. Utilizing advanced Hamiltonian engineering techniques to explore a range of spin Hamiltonians, we observe a striking change in the characteristic shape and timescale of local correlation decay as we vary the engineered exchange anisotropy. We show that these observations originate from the system's intrinsic many-body dynamics and reveal the signatures of conservation laws within localized clusters of spins, which do not readily manifest using global probes. Our method provides an exquisite lens into the tunable nature of local thermalization dynamics and enables detailed studies of scrambling, thermalization, and hydrodynamics in strongly interacting quantum systems.


Asunto(s)
Hidrodinámica , Física , Anisotropía
6.
BMC Public Health ; 17(1): 413, 2017 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-28482868

RESUMEN

BACKGROUND: According to the World Health Organization, drowning is the 3rd leading cause of unintentional injury-related deaths worldwide, accounting for 370,000 annual deaths and 7% of all injury-related deaths. Low- and middle-income countries are the most affected, accounting for 91% of unintentional drowning deaths. METHODS: The authors performed a systematic review of literature indexed in EMBASE, PubMed, Web of Science, Cochrane Library, and Traumatology journals formerly indexed in PubMed in January 2014 and again in September 2016. Abstracts were limited to human studies in English, conducted in low- and middle-income countries, and containing quantitative data on drowning epidemiology. RESULTS: A total of 62 articles met inclusion criteria. The majority of articles originate from Asia (56%) and Africa (26%). Risk factors for drowning included young age (<17-20 years old), male gender (75% vs. 25% female), rural environment (84% vs. 16% urban), occurring in the daytime (95% vs. 5% night time), lack of adult supervision (76% vs. 18% supervised), and limited swimming ability (86% vs. 10% with swimming ability). There was almost equal risk of drowning in a small body of water versus a large body of water (42% ponds, ditches, streams, wells; 46% lakes, rivers, sea, ocean). CONCLUSION: Drowning is a significant cause of injury-related deaths, especially in LMICs. Young males who are unsupervised in rural areas and have limited formal swimming instruction are at greatest risk of drowning in small bodies of water around their homes. Preventative strategies include covering wells and cisterns, fencing off ditches and small ponds, establishing community daycares, providing formal swimming lessons, and increasing awareness of the risks of drowning.


Asunto(s)
Ahogamiento/epidemiología , Distribución por Edad , Países en Desarrollo/estadística & datos numéricos , Humanos , Ríos , Distribución por Sexo , Pozos de Agua
7.
Qual Health Res ; 26(14): 1949-1960, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26481944

RESUMEN

The purpose of this study was to investigate perceptions of health and health behaviors among Indigenous Australian men. Using a participatory action research (PAR) framework, we conducted two focus groups and 40 individual semi-structured interviews with men between the ages of 18 and 35 years in each of three locations across Australia. We used the health beliefs model to provide a framework for the analyses. Participants recognized that their Indigenous status placed them in a vulnerable position with regard to health, and that there might be serious consequences of failing to follow a good diet and engage in appropriate exercise. However, they delineated a number of barriers to engaging in such health behaviors. These perceived barriers require addressing at a range of policy levels within government, with a focus on social structures and institutionalized discrimination, as well as unemployment, poverty, dispossession, and cultural oppression.


Asunto(s)
Conductas Relacionadas con la Salud , Estado de Salud , Adolescente , Adulto , Australia , Grupos Focales , Humanos , Masculino , Nativos de Hawái y Otras Islas del Pacífico , Adulto Joven
8.
Ann Otol Rhinol Laryngol ; 133(3): 261-267, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37800544

RESUMEN

INTRODUCTION: Maxillomandibular advancement (MMA) remains an effective procedure for the management of obstructive sleep apnea (OSA). Maxillary advancement may lead to anatomical changes that impair paranasal sinus drainage, leading to chronic sinus inflammation. The aim of this study was to describe the clinical features and outcomes of patients suffering from chronic rhinosinusitis (CRS) following MMA. METHODS: This is a retrospective case series study. Our study included subjects diagnosed with CRS following MMA from January 1992 to October 2018 at Stanford Hospital. We screened 730 patients undergoing MMA and identified a total of 57 with CRS after MMA. A descriptive analysis was performed using clinical data including patient demographics, comorbidities, prior surgical history, physical exam manifestations, CT findings, and quality of life outcomes (SNOT-22). RESULTS: Out of 730 patients undergoing MMA, 57(7.8%) were found to have CRS after orthognathic surgery. Presenting symptoms included facial pain (92.5%), nasal drainage (75%), nasal obstruction (67.5%), and hyposmia (20%). Endoscopic examination revealed recirculation (30.5%), purulent discharge (27.7%), polypoid changes (22.2%), and scarring (13.8%). Preoperative CT prior to undergoing endoscopic sinus surgery (ESS) demonstrated mucosal thickening in maxillary (64.2%), anterior ethmoid (39.2%), frontal (14.2%), posterior ethmoid (10.7%), sphenoid sinus (14.2%), and ostiomeatal complex (55.3%). Average Lund-Mackay score was 5.5(±3.8). Additional CT findings included secondary ostium in the inferior meatus (42.8%). Forty patients (70.1%) underwent ESS at a mean of 4.6 years after MMA. Patients undergoing ESS experienced significant improvement in SNOT-22 scores at 12-months post-surgery (P = .018). CONCLUSION: Patients undergoing maxillary advancement surgery are at risk of developing CRS postoperatively and should be advised of the risk of CRS associated with this procedure. Surgical treatment can be an option for medically refractory CRS related to MMA surgery.


Asunto(s)
Cirugía Ortognática , Rinitis , Rinosinusitis , Sinusitis , Humanos , Estudios Retrospectivos , Calidad de Vida , Sinusitis/diagnóstico , Sinusitis/cirugía , Enfermedad Crónica , Endoscopía/efectos adversos , Endoscopía/métodos , Inflamación , Rinitis/diagnóstico , Rinitis/cirugía , Resultado del Tratamiento
9.
Laryngoscope ; 134(3): 1096-1099, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37578267

RESUMEN

OBJECTIVE: The anterior ethmoidal artery (AEA) is an important structure to identify during endoscopic sinus surgery. Although identification on imaging is easily taught, a consistent endoscopic landmark for the AEA, independent of anatomic ethmoid cell variation, is lacking, leaving many surgeons unclear about the exact location without dependence on navigation. Here, we describe a consistent endoscopic landmark, regardless of anatomical ethmoid variation. METHODS: We prospectively enrolled adult patients undergoing endoscopic surgery involving frontal and ethmoid sinuses in this observational study. The AEA landmark was defined simply as the septation or ridge one step back along the ethmoid skull base from the posterior table of the frontal sinus. The gold standard to calculate the sensitivity of our endoscopic landmark was an image-navigation system, registered to within 1.5 mm accuracy, locating the AEA within three planes. Both endoscopic and computerized tomography (CT) images of the pointer at the landmark were taken simultaneously. The concordance of endoscopic to navigation images was independently assessed by three blinded rhinologists. RESULTS: Forty patients were included in our study with 73 sides analyzed. Diagnoses included chronic rhinosinusitis without polyps (52.5%), with polyps (22.5%), recurrent acute sinusitis (15%), sinonasal tumors (7.5%), and odontogenic sinusitis (2.5%). The AEA was accurately identified using our endoscopic landmark in 97.3% of the cases (71/73). Of the two cases in which the AEA was not found within the landmark, the artery was located ≤1 mm posteriorly. CONCLUSION: We describe a consistent endoscopic landmark to identify the AEA, conserved across various clinical diagnoses and anatomic variations in sinus structure. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1096-1099, 2024.


Asunto(s)
Sinusitis , Base del Cráneo , Adulto , Humanos , Base del Cráneo/cirugía , Arterias/cirugía , Hueso Etmoides , Senos Etmoidales/diagnóstico por imagen , Senos Etmoidales/cirugía , Senos Etmoidales/irrigación sanguínea , Endoscopía/métodos
10.
Ann Otol Rhinol Laryngol ; 133(5): 476-484, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38345045

RESUMEN

OBJECTIVES: Variations in management of sinusitis in primary care settings can be associated with inappropriate antibiotic prescriptions and delays in treatment. The objective of this study was to identify patient and provider characteristics associated with possible inaccurate diagnosis and management of sinusitis. METHODS: We performed a cross-sectional retrospective analysis using an established regional healthcare database of patients who received a diagnosis of sinusitis between 2011 and 2022 from a non-otolaryngologist provider. Patient's comorbidities, insurance status, chronicity of sinusitis, and prescriptions were included. We noted if patients were referred to an otolaryngology practice and if they received a diagnosis of sinusitis from an otolaryngologist. RESULTS: We analyzed 99 581 unique patients and 168 137 unique encounters. The mean age was 41.5 (±20.4 years) and 35.7% were male. Most patients had private insurance (88.5%), acute sinusitis (81.2%), and were seen at a primary care office (97.8%). Approximately 30% of patients were referred to an otolaryngology practice for sinusitis. Of referred patients, 50.6% did not receive a diagnosis of sinusitis from an otolaryngology practice. Patients without a sinusitis diagnosis by an otolaryngology practice received significantly more mean courses of antibiotics (5.04 vs 2.39, P < .0001) and oral steroids (3.53 vs 2.08, P < .0001). CONCLUSIONS: Over half of the patients referred to an otolaryngology practice from primary care for sinusitis did not receive a diagnosis of sinusitis from an otolaryngology practice. Further research should investigate implications for increased healthcare costs and inappropriate prescription trends associated with the management of sinusitis.


Asunto(s)
Otolaringología , Sinusitis , Humanos , Masculino , Adulto , Femenino , Estudios Transversales , Estudios Retrospectivos , Pautas de la Práctica en Medicina , Sinusitis/terapia , Sinusitis/tratamiento farmacológico , Atención Primaria de Salud , Antibacterianos/uso terapéutico
11.
Int Forum Allergy Rhinol ; 14(1): 78-85, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37389470

RESUMEN

BACKGROUND: Budesonide irrigations (BIs) are commonly used to control inflammation in chronic rhinosinusitis (CRS). In 2016 we reported an analysis of long-term BI with regard to hypothalamic-pituitary-adrenal axis function. We present a follow-up analysis in a larger cohort of patients with longer follow-up. METHODS: Patients were candidates for stimulated cortisol testing after regularly performing BI for CRS at least daily for ≥6 months. We retrospectively evaluated all patients who received stimulated cortisol testing at our center between 2012 and 2022. We correlated cortisol levels with the use of BI and other forms of corticosteroids. RESULTS: We analyzed 401 cortisol test results in 285 patients. The mean duration of use was 34 months. Overall, 21.8% of patients were hypocortisolemic (<18 ug/dL) at first test. In patients who used only BI, the rate of hypocortisolemia was 7.5%, whereas in patients who also used concurrent oral and inhaled corticosteroids, the rate was 40% to 50%. Lower cortisol levels were associated with male sex (p < 0.0001) and concomitant use of oral and inhaled steroids (p < 0.0001). Duration of BI use was not significantly associated with lower cortisol levels (p = 0.701), nor was greater dosing frequency (p = 0.289). CONCLUSION: Prolonged use of BI alone is not likely to cause hypocortisolemia in the majority of patients. However, concomitant use of inhaled and oral steroids and male sex may be associated with hypocortisolemia. Surveillance of cortisol levels may be considered in vulnerable populations who use BI regularly, particularly in patients using other forms of corticosteroids with known systemic absorption.


Asunto(s)
Rinosinusitis , Sinusitis , Humanos , Masculino , Budesonida/efectos adversos , Hidrocortisona , Sistema Hipotálamo-Hipofisario , Incidencia , Estudios Retrospectivos , Sistema Hipófiso-Suprarrenal , Corticoesteroides/efectos adversos , Sinusitis/tratamiento farmacológico , Sinusitis/epidemiología , Sinusitis/inducido químicamente , Administración por Inhalación
13.
World Neurosurg ; 173: e132-e139, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36773809

RESUMEN

OBJECTIVE: To examine the demographics, tumor characteristics, treatments, and clinical outcomes of a large adult craniopharyngioma population. METHODS: The 2004-2018 National Cancer Database was queried to investigate adult patients with craniopharyngioma. Univariable and multivariable Cox hazard ratio analysis was conducted to analyze the overall survival (OS) impact of demographic and clinical variables. RESULTS: A total of 666 adult patients with craniopharyngioma were identified with a mean age of 51 years (standard deviation 16 years). On multivariable analysis, independent of demographic and clinical variables, increased age, uninsured status, Medicaid, Medicare, Charlson-Deyo Comorbidity Index of 2, and tumor size greater than 40 mm were independently associated with worse OS. There was no significant difference in survival between histologic subtypes. Gross total resection (GTR) (hazard ratio [HR] 0.602, 95% confidence interval [CI] 0.384-0.942, P = 0.026) and subtotal resection (STR) with adjuvant radiotherapy (HR 0.316, 95% CI 0.140-0.710, P = 0.005) were independently associated with improved OS. GTR with radiotherapy trended towards improved OS (HR 0.601, 95% CI 0.334-1.083, P =0.090), but STR alone and radiotherapy alone demonstrated no significant difference in survival compared with no treatment on multivariable analysis. Kaplan-Meier survival models demonstrated improved survival with GTR, GTR + radiation therapy, and STR + radiation therapy. Patients undergoing endoscopic resection had significantly lower GTR rates and greater rates of adjuvant radiotherapy compared with open approaches but no difference in OS. CONCLUSION: Adult patients with craniopharyngioma who underwent GTR or STR with adjuvant radiotherapy had significantly improved overall survival. Endoscopic approaches had lower rates of GTR but no difference in OS.


Asunto(s)
Craneofaringioma , Neoplasias Hipofisarias , Adulto , Humanos , Anciano , Estados Unidos/epidemiología , Persona de Mediana Edad , Craneofaringioma/cirugía , Craneofaringioma/patología , Resultado del Tratamiento , Pronóstico , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Medicare , Radioterapia Adyuvante , Estudios Retrospectivos
15.
BMC Public Health ; 12: 28, 2012 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-22236166

RESUMEN

BACKGROUND: Overall the physical health of Indigenous men is among the worst in Australia. Research has indicated that modifiable lifestyle factors, such as poor nutrition and physical inactivity, appear to contribute strongly to these poor health conditions. To effectively develop and implement strategies to improve the health of Australia's Indigenous peoples, a greater understanding is needed of how Indigenous men perceive health, and how they view and care for their bodies. Further, a more systematic understanding of how sociocultural factors affect their health attitudes and behaviours is needed. This article presents the study protocol of a community-based investigation into the factors surrounding the health and body image of Indigenous Australian men. METHODS AND DESIGN: The study will be conducted in a collaborative manner with Indigenous Australian men using a participatory action research framework. Men will be recruited from three locations around Australia (metropolitan, regional, and rural) and interviewed to understand their experiences and perspectives on a number of issues related to health and health behaviour. The information that is collected will be analysed using modified grounded theory and thematic analysis. The results will then be used to develop and implement community events in each location to provide feedback on the findings to the community, promote health enhancing strategies, and determine future action and collaboration. DISCUSSION: This study will explore both risk and protective factors that affect the health of Indigenous Australian men. This knowledge will be disseminated to the wider Indigenous community and can be used to inform future health promotion strategies. The expected outcome of this study is therefore an increased understanding of health and health change in Indigenous Australian men, the development of strategies that promote healthy eating and positive patterns of physical activity and, in the longer term, more effective and culturally-appropriate interventions to improve health.


Asunto(s)
Conductas Relacionadas con la Salud/etnología , Conocimientos, Actitudes y Práctica en Salud/etnología , Promoción de la Salud/métodos , Servicios de Salud del Indígena/organización & administración , Nativos de Hawái y Otras Islas del Pacífico/psicología , Aptitud Física , Aculturación , Adolescente , Adulto , Australia , Imagen Corporal , Dieta/etnología , Identidad de Género , Estado de Salud , Humanos , Masculino , Actividad Motora , Investigación Cualitativa , Proyectos de Investigación , Factores de Riesgo , Adulto Joven
16.
J Neurol Surg B Skull Base ; 83(Suppl 2): e152-e159, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35832980

RESUMEN

Background Pituitary apoplexy after resection of giant pituitary adenomas is a rare but often cited morbidity associated with devastating outcomes. It presents as hemorrhage and/or infarction of residual tumor in the postoperative period. Because of its rarity, its incidence and consequences remain ill defined. Objective The aim of this study is to estimate the rate of postoperative pituitary apoplexy after resection of giant pituitary adenomas and assess the morbidity and mortality associated with apoplexy. Methods A systematic review of literature was performed to examine extent of resection in giant pituitary adenomas based on surgical approach, rate of postoperative apoplexy, morbidities, and mortality. Advantages and disadvantages of each approach were compared. Results Seventeen studies were included in quantitative analysis describing 1,031 cases of resection of giant pituitary adenomas. The overall rate of subtotal resection (<90%) for all surgical approaches combined was 35.6% (95% confidence interval: 28.0-43.1). Postoperative pituitary apoplexy developed in 5.65% ( n = 19) of subtotal resections, often within 24 hours and with a mortality of 42.1% ( n = 8). Resulting morbidities included visual deficits, altered consciousness, cranial nerve palsies, and convulsions. Conclusion Postoperative pituitary apoplexy is uncommon but is associated with high rates of morbidity and mortality in subtotal resection cases. These findings highlight the importance in achieving a maximal resection in a time sensitive fashion to mitigate the severe consequences of postoperative apoplexy.

17.
Oral Oncol ; 134: 106127, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36155359

RESUMEN

OBJECTIVES: We sought to determine overall survival (OS), prognostic factors, cost, and functional outcomes after surgery for locally recurrent oral cavity squamous cell carcinoma (OCSCC). MATERIALS AND METHODS: We retrospectively reviewed 399 cases of locally recurrent OCSCC from 1997 to 2011, of which 259 patients were treated with salvage surgery. Survival and prognostic factors were evaluated using univariable and multivariable Cox regression, the Kaplan-Meier method, and the log-rank test. RESULTS: The 5-year OS for patients undergoing surgical salvage, nonsurgical therapy, or supportive care was 44.2%, 1.5%, and 0%, respectively. For patients who underwent surgical salvage, 133 (51%) patients experienced a second recurrence at a median of 17 months. Factors associated with OS included disease-free interval ≤ 6 months (P =.0001), recurrent stage III-IV disease (P <.0001), and prior radiation (P =.0001). Patients with both advanced stage and prior radiation had a 23% 5-year OS, compared with 70% for those with neither risk (P <.001). Functionally, 85% of patients had > 80% speech intelligibility and 81% were able to eat by mouth following salvage surgery. Of the patients who required tracheostomy, 78% were decannulated. The adjusted median hospital and professional charges for patients were $129,696 (range $9,238-$956,818). CONCLUSIONS: Patients with recurrent OCSCC who underwent salvage surgery have favorable functional outcomes with half of alive at 5 years but poorer OS for advanced disease, disease-free interval ≤ 6 months, and prior radiation. Additionally, treatment is associated with high cost, and about half of patients ultimately develop another recurrence.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Carcinoma de Células Escamosas/cirugía , Humanos , Neoplasias de la Boca/cirugía , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Terapia Recuperativa/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello , Tasa de Supervivencia
18.
Mol Pharm ; 8(5): 1559-72, 2011 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-21718006

RESUMEN

Glioblastoma multiforme is a primary malignancy of the central nervous system that is universally fatal due to its disseminated nature. Recent investigations have focused on the unique tumor-tropic properties of stem cells as a novel platform for targeted delivery of anticancer agents to the brain. Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) both have the potential to function as cell carriers for targeted delivery of a glioma restricted oncolytic virus to disseminated tumor due to their reported tumor tropism. In this study, we evaluated NSCs and MSCs as cellular delivery vehicles for an oncolytic adenovirus in the context of human glioma. We report the first preclinical comparison of the two cell lines and show that, while both stem cell lines are able to support therapeutic adenoviral replication intracellularly, the amount of virus released from NSCs was a log higher than the MSC (p < 0.001). Moreover, only virus loaded NSCs that were administered intracranially in an orthotopic glioma model significantly prolonged the survival of tumor bearing animals (median survival for NSCs 68.5 days vs 44 days for MSCs, p < 0.002). Loading oncolytic adenovirus into NSCs and MSCs also led to expression of both pro- and anti-inflammatory genes and decreased vector-mediated neuroinflammation. Our results indicate that, despite possessing a comparable migratory capacity, NSCs display superior therapeutic efficacy in the context of intracranial tumors. Taken together, these findings argue in favor of NSCs as an effective cell carrier for antiglioma oncolytic virotherapy.


Asunto(s)
Adenoviridae/fisiología , Neoplasias Encefálicas/terapia , Glioma/terapia , Trasplante de Células Madre Mesenquimatosas , Células-Madre Neurales/trasplante , Viroterapia Oncolítica/métodos , Virus Oncolíticos/fisiología , Adenoviridae/patogenicidad , Infecciones por Adenoviridae/inmunología , Infecciones por Adenoviridae/fisiopatología , Infecciones por Adenoviridae/virología , Animales , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Encefalitis Viral/inmunología , Encefalitis Viral/fisiopatología , Encefalitis Viral/virología , Glioma/inmunología , Glioma/patología , Humanos , Masculino , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/virología , Ratones , Ratones Desnudos , Células-Madre Neurales/virología , Viroterapia Oncolítica/efectos adversos , Virus Oncolíticos/patogenicidad , Distribución Aleatoria , Análisis de Supervivencia , Células Tumorales Cultivadas , Liberación del Virus , Replicación Viral , Ensayos Antitumor por Modelo de Xenoinjerto
19.
Mol Ther ; 18(10): 1846-56, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20588259

RESUMEN

Oncolytic adenoviral virotherapy is an attractive treatment modality for cancer. However, following intratumoral injections, oncolytic viruses fail to efficiently migrate away from the injection site and are rapidly cleared by the immune system. We have previously demonstrated enhanced viral delivery and replicative persistence in vivo using human bone marrow-derived mesenchymal stem cells (MSCs) as delivery vehicles. In this study, we evaluated the immune response to adenovirus (Ad)-loaded MSCs using the semipermissive cotton rat (CR) model. First, we isolated MSCs from CR bone marrow aspirates. Real-time quantitative PCR analysis revealed that CR MSCs supported the replication of Ads in vitro. Moreover, we observed similar levels of suppression of T-cell proliferation in response to mitogenic stimulation, by MSCs alone and virus-loaded MSCs. Additionally, we found that MSCs suppressed the production of interferon-γ (IFN-γ) by activated T cells. In our in vivo model, CR MSCs enhanced the dissemination and persistence of Ad, compared to virus injection alone. Collectively, our data suggest that the use of MSCs as a delivery strategy for oncolytic Ad potentially offers a myriad of benefits, including improved delivery, enhanced dissemination, and increased persistence of viruses via suppression of the antiviral immune response.


Asunto(s)
Adenoviridae/inmunología , Células Madre Mesenquimatosas/inmunología , Viroterapia Oncolítica/métodos , Adenoviridae/genética , Animales , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/metabolismo , Proliferación Celular , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Humanos , Interferón gamma/metabolismo , Activación de Linfocitos/inmunología , Masculino , Células Madre Mesenquimatosas/metabolismo , Ratas , Sigmodontinae
20.
Crit Care Explor ; 3(5): e0413, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33977277

RESUMEN

Advance directives can help guide care in the ICU. As a healthcare quality improvement initiative, we sought to increase the percentage of patients with a healthcare power of attorney and/or practitioner orders for life-sustaining treatment in our ICU and to increase medical resident experience with advance directives through routine screening and documentation of advance directives in the ICU. DESIGN: Prospective analysis. SETTING: Urban U.S. community teaching hospital. PATIENTS: All patients admitted to the ICU from September 2018 to February 2019. INTERVENTIONS: Internal medicine residents in the ICU received a lecture about advance directives and instructions to screen their patients for advance directives. For willing and decisional patients, residents facilitated the creation of a healthcare power of attorney and/or practitioner orders for life-sustaining treatment. Residents were anonymously surveyed at the beginning and end of the ICU rotation about their experience and level of comfort with healthcare power of attorney and practitioner orders for life-sustaining treatment completion. MEASUREMENTS AND MAIN RESULTS: Three-hundred seventy-five patients were admitted to the ICU during the study period. Healthcare power of attorney documents were generated by 34% of all ICU patients without a prior healthcare power of attorney, increased from a baseline rate of 10% (p < 0.001). The number of practitioner orders for life-sustaining treatment documents for patients with code status of "no cardiopulmonary resuscitation" did not increase significantly. The percentage of residents who facilitated completion of a healthcare power of attorney document increased significantly from 56% to 100% (p < 0.001), whereas their practitioner orders for life-sustaining treatment experience did not change significantly by the end of their ICU rotation. On a Likert scale of 0-10, mean resident comfort increased significantly both with healthcare power of attorney documentation, rising from 6.14 to 8.84 (p = 0.005) and with practitioner orders for life-sustaining treatment form completion, increasing from 6.00 to 7.84 (p = 0.008). CONCLUSIONS: Training ICU medical residents to routinely screen for and facilitate completion of advance directives significantly increased the percentage of ICU patients with a healthcare power of attorney and significantly improved medical resident comfort with healthcare power of attorney and practitioner orders for life-sustaining treatment form completion.

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