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1.
Environ Monit Assess ; 195(2): 345, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36715872

RESUMEN

Regulating the fuel consumption of small-scale fishing vessels could help to keep global warming well below 1.5 °C and lead to effective management in small-scale fisheries (SSF) of developing countries like India. In this regard, a bottom-up approach was carried out to collect the requisite data to explore the fuel consumption of small-scale fishing vessels along India's southeast coast. Consequently, twenty-four fishing vessels (type A to type X) were grouped into seven categories based on fishing methods. The estimated numerical value of fuel use intensity (FUI) ranging from 0.08 to 0.80 was used to examine the fuel-efficient fishing vessel and engine type. In addition, the estimated revenue on fuel ranging from ₹5625.06/l to ₹218.07/l and annual greenhouse gas (GHG) emissions using the Tier 1 method were used to understand the economic efficiency and GHG emission trend, respectively. The total annual GHG emissions from all the fishing vessels at the selected sites were about 1.25E + 08 t CO2-eq year-1. The result shows that longline-cum-gillnetters, seine-netters, longliners and drift-gillnetters largely contributed to 65% of the annual GHG emissions. By recognizing the factors influencing the fuel consumption of fishing vessels in SSF, this sector could be understood, effectively managed, and performed well. Therefore, the possible reasons were extensively discussed through a comparative approach, and potential recommendations for effective management were made.


Asunto(s)
Efecto Invernadero , Gases de Efecto Invernadero , Caza , Monitoreo del Ambiente , India
2.
Wound Repair Regen ; 30(1): 24-33, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34698428

RESUMEN

Australia has the second highest rate of non-traumatic lower extremity amputation (LEA) globally. Australia's large geographical size is one of the biggest challenges facing limb preservation services and may be contributing to LEA. The aim of this study was to determine what factors contribute to the likelihood of LEA in people with active foot ulceration in regional Australia. This retrospective cohort study audited patients with active foot ulceration in a multidisciplinary high risk foot service (HRFS) in regional Australia. Neurological, vascular and wound characteristics were systematically extracted, along with demographic information. Participants were followed for at least 12 months until healing or LEA occurred. Correlations between LEA and clinical and demographic characteristics were assessed using the Pearson's product moment correlation coefficient and chi squared test for independence. Significant variables (p < 0.05) were included in the model. Direct logistic regression assessed the independent contribution of significantly correlated variables on the likelihood of LEA. Of note, 1876 records were hand screened with 476 participants (25%) meeting the inclusion criteria. Geographical distance from the HRFS, toe systolic pressure (TSP), diabetes and infection were all significantly correlated with LEA and included in the logistic regression model. TSP decrease of 1 mmHg (OR 1.02, 95% CI 1.01-1.03), increased geographical distance (1 km) from HRFS (OR 1.006, 95% CI 1.001-1.01) infection (OR 2.08, 95% CI 1.06-4.07) and presence of diabetes (OR 3.77, 95% CI 1.12-12.65) were all significantly associated with increased likelihood of LEA. HRFS should account for the disparity in outcomes between patients living in close proximity to their service, compared to those in rural areas. Optimal management of diabetes, vascular perfusion and control of infection may also contribute to preventing LEA in people with active foot ulceration.


Asunto(s)
Pie Diabético , Amputación Quirúrgica , Pie Diabético/epidemiología , Pie Diabético/cirugía , Humanos , Extremidad Inferior/cirugía , Estudios Retrospectivos , Factores de Riesgo , Cicatrización de Heridas
3.
Vasc Med ; 23(2): 116-125, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29432708

RESUMEN

The postexercise ankle-brachial index (ABI) is recommended in patients with normal resting ABI when peripheral artery disease (PAD) is suspected. The aims of this study were to determine the comparative diagnostic accuracy of the resting and postexercise ABI for detecting PAD, and, the effect of the presence of diabetes on these. Three methods of interpretation currently in use were also investigated: a reduction in postexercise ABI by >20% compared to resting ABI, an ABI value of ≤0.90 postexercise, or a reduction in systolic ankle pressure of >30 mmHg postexercise. This retrospective study used colour duplex ultrasound (CDU) as the reference standard. In 278 limbs (whole group), the resting ABI had an overall area under the curve (AUC) of 0.71, with the postexercise ABI yielding a similar diagnostic accuracy of AUC 0.72. In the non-diabetes group ( n=171), the resting ABI had an overall AUC of 0.74 and the postexercise ABI had a similar AUC of 0.76. In the diabetes group ( n=107), overall accuracy was reduced compared to the non-diabetes group, with the resting ABI having an overall AUC of 0.65 and the postexercise ABI yielding a similar accuracy with an AUC of 0.64. The overall diagnostic accuracy of the postexercise ABI for diagnosing PAD was not greatly improved compared to resting ABI. Given the lower overall diagnostic accuracy in the diabetes group, both the resting and the postexercise ABI results in diabetes populations should be interpreted with caution. There is a risk of undiagnosed disease if relying on these results alone to determine lower limb vascular status.


Asunto(s)
Índice Tobillo Braquial , Arteria Braquial/diagnóstico por imagen , Extremidad Inferior/fisiopatología , Enfermedad Arterial Periférica/diagnóstico , Anciano , Anciano de 80 o más Años , Tobillo/irrigación sanguínea , Presión Sanguínea/fisiología , Diabetes Mellitus/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/fisiopatología , Descanso/fisiología , Estudios Retrospectivos
4.
J Immunol ; 196(1): 144-55, 2016 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-26582951

RESUMEN

A subpopulation (60-70%) of Foxp3(+) regulatory T cells (Tregs) in both mouse and man expresses the transcription factor Helios, but its role in Treg function is still unknown. We generated Treg-specific Helios-deficient mice to examine the function of Helios in Tregs. We show that the selective deletion of Helios in Tregs leads to slow, progressive systemic immune activation, hypergammaglobulinemia, and enhanced germinal center formation in the absence of organ-specific autoimmunity. Helios-deficient Treg suppressor function was normal in vitro, as well as in an in vivo inflammatory bowel disease model. However, Helios-deficient Tregs failed to control the expansion of pathogenic T cells derived from scurfy mice, failed to mediate T follicular regulatory cell function, and failed to control both T follicular helper cell and Th1 effector cell responses. In competitive settings, Helios-deficient Tregs, particularly effector Tregs, were at a disadvantage, indicating that Helios regulates effector Treg fitness. Thus, we demonstrate that Helios controls certain aspects of Treg-suppressive function, differentiation, and survival.


Asunto(s)
Enfermedades Autoinmunes/genética , Proteínas de Unión al ADN/genética , Factores de Transcripción Forkhead/genética , Linfocitos T Reguladores/inmunología , Factores de Transcripción/genética , Animales , Enfermedades Autoinmunes/inmunología , Autoinmunidad/genética , Autoinmunidad/inmunología , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Proteínas de Unión al ADN/inmunología , Modelos Animales de Enfermedad , Femenino , Factores de Transcripción Forkhead/inmunología , Centro Germinal/inmunología , Hipergammaglobulinemia/genética , Hipergammaglobulinemia/inmunología , Factor de Transcripción Ikaros/inmunología , Enfermedades Inflamatorias del Intestino/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Linfocitos T Reguladores/citología , Células TH1/inmunología , Factores de Transcripción/inmunología
6.
Am Nat ; 184 Suppl 1: S77-90, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25061679

RESUMEN

Parasite prevalence shows tremendous spatiotemporal variation. Theory indicates that this variation might stem from life-history characteristics of parasites and key ecological factors. Here, we illustrate how the interaction of an important predator and the schedule of transmission potential of two parasites can explain parasite abundance. A field survey showed that a noncastrating fungus (Metschnikowia bicuspidata) commonly infected a dominant zooplankton host (Daphnia dentifera), while a castrating bacterial parasite (Pasteuria ramosa) was rare. This result seemed surprising given that the bacterium produces many more infectious propagules (spores) than the fungus upon host death. The fungus's dominance can be explained by the schedule of within-host growth of parasites (i.e., how transmission potential changes over the course of infection) and the release of spores from "sloppy" predators (Chaoborus spp., who consume Daphnia prey whole and then later regurgitate the carapace and parasite spores). In essence, sloppy predators create a niche that the faster-schedule fungus currently occupies. However, a selection experiment showed that the slower-schedule bacterium can evolve into this faster-schedule, predator-mediated niche (but pays a cost in maximal spore yield to do so). Hence, our study shows how parasite life history can interact with predation to strongly influence the ecology, epidemiology, and evolution of infectious disease.


Asunto(s)
Evolución Biológica , Daphnia/microbiología , Daphnia/parasitología , Ecología , Interacciones Huésped-Patógeno/genética , Pasteuria/patogenicidad , Animales , Chironomidae , Indiana , Estadios del Ciclo de Vida , Metschnikowia/fisiología , Michigan , Pasteuria/genética , Conducta Predatoria
7.
Cancer Immunol Res ; 12(10): 1340-1360, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39051633

RESUMEN

Immunotherapy has limited efficacy in glioblastoma (GBM) due to the blood-brain barrier and the immunosuppressed or "cold" tumor microenvironment (TME) of GBM, which is dominated by immune-inhibitory cells and depleted of CTL and dendritic cells (DC). Here, we report the development and application of a machine learning precision method to identify cell fate determinants (CFD) that specifically reprogram GBM cells into induced antigen-presenting cells with DC-like functions (iDC-APC). In murine GBM models, iDC-APCs acquired DC-like morphology, regulatory gene expression profile, and functions comparable to natural DCs. Among these acquired functions were phagocytosis, direct presentation of endogenous antigens, and cross-presentation of exogenous antigens. The latter endowed the iDC-APCs with the ability to prime naïve CD8+ CTLs, a hallmark DC function critical for antitumor immunity. Intratumor iDC-APCs reduced tumor growth and improved survival only in immunocompetent animals, which coincided with extensive infiltration of CD4+ T cells and activated CD8+ CTLs in the TME. The reactivated TME synergized with an intratumor soluble PD1 decoy immunotherapy and a DC-based GBM vaccine, resulting in robust killing of highly resistant GBM cells by tumor-specific CD8+ CTLs and significantly extended survival. Lastly, we defined a unique CFD combination specifically for the human GBM to iDC-APC conversion of both glioma stem-like cells and non-stem-like cell GBM cells, confirming the clinical utility of a computationally directed, tumor-specific conversion immunotherapy for GBM and potentially other solid tumors.


Asunto(s)
Células Dendríticas , Glioblastoma , Inmunoterapia , Aprendizaje Automático , Glioblastoma/inmunología , Glioblastoma/terapia , Glioblastoma/patología , Animales , Células Dendríticas/inmunología , Humanos , Ratones , Inmunoterapia/métodos , Microambiente Tumoral/inmunología , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Células Presentadoras de Antígenos/inmunología , Línea Celular Tumoral , Ratones Endogámicos C57BL
8.
J Immunother Cancer ; 11(2)2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36750252

RESUMEN

BACKGROUND: Glioma-induced immune dysregulation of the hematopoietic system has been described in a limited number of studies. In this study, our group further demonstrates that gliomas interrupt the cellular differentiation programming and outcomes of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. HSPCs from glioma-bearing mice are reprogrammed and driven towards expansion of myeloid lineage precursors and myeloid-derived suppressor cells (MDSCs) in secondary lymphoid organs. However, we found this expansion is reversed by immunotherapy. Adoptive cellular therapy (ACT) has been demonstrably efficacious in multiple preclinical models of central nervous system (CNS) malignancies, and here we describe how glioma-induced dysfunction is reversed by this immunotherapeutic platform. METHODS: The impact of orthotopic KR158B-luc glioma on HSPCs was evaluated in an unbiased fashion using single cell RNAseq (scRNAseq) of lineage- cells and phenotypically using flow cytometry. Mature myeloid cell frequencies and function were also evaluated using flow cytometry. Finally, ACT containing total body irradiation, tumor RNA-pulsed dendritic cells, tumor-reactive T cells and HSPCs isolated from glioma-bearing or non-tumor-bearing mice were used to evaluate cell fate differentiation and survival. RESULTS: Using scRNAseq, we observed an altered HSPC landscape in glioma-bearing versus non-tumor-bearing mice . In addition, an expansion of myeloid lineage subsets, including granulocyte macrophage precursors (GMPs) and MDSCs, were observed in glioma-bearing mice relative to non-tumor-bearing controls. Furthermore, MDSCs from glioma-bearing mice demonstrated increased suppressive capacity toward tumor-specific T cells as compared with MDSCs from non-tumor-bearing hosts. Interestingly, treatment with ACT overcame these suppressive properties. When HSPCs from glioma-bearing mice were transferred in the context of ACT, we observed significant survival benefit and long-term cures in orthotopic glioma models compared with mice treated with ACT using non-glioma-bearing HSPCs.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Glioma , Ratones , Animales , Línea Celular Tumoral , Glioma/patología , Inmunoterapia , Células Madre Hematopoyéticas , Linfocitos T
9.
J Clin Invest ; 132(8)2022 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-35199647

RESUMEN

Tumor Treating Fields (TTFields), an approved therapy for glioblastoma (GBM) and malignant mesothelioma, employ noninvasive application of low-intensity, intermediate-frequency, alternating electric fields to disrupt the mitotic spindle, leading to chromosome missegregation and apoptosis. Emerging evidence suggests that TTFields may also induce inflammation. However, the mechanism underlying this property and whether it can be harnessed therapeutically are unclear. Here, we report that TTFields induced focal disruption of the nuclear envelope, leading to cytosolic release of large micronuclei clusters that intensely recruited and activated 2 major DNA sensors - cyclic GMP-AMP synthase (cGAS) and absent in melanoma 2 (AIM2) - and their cognate cGAS/stimulator of interferon genes (STING) and AIM2/caspase 1 inflammasomes to produce proinflammatory cytokines, type 1 interferons (T1IFNs), and T1IFN-responsive genes. In syngeneic murine GBM models, TTFields-treated GBM cells induced antitumor memory immunity and a cure rate of 42% to 66% in a STING- and AIM2-dependent manner. Using single-cell and bulk RNA sequencing of peripheral blood mononuclear cells, we detected robust post-TTFields activation of adaptive immunity in patients with GBM via a T1IFN-based trajectory and identified a gene panel signature of TTFields effects on T cell activation and clonal expansion. Collectively, these studies defined a therapeutic strategy using TTFields as cancer immunotherapy in GBM and potentially other solid tumors.


Asunto(s)
Proteínas de Unión al ADN , Glioblastoma , Melanoma , Proteínas de la Membrana , Animales , Proteínas de Unión al ADN/genética , Glioblastoma/patología , Glioblastoma/terapia , Humanos , Inflamasomas , Leucocitos Mononucleares/patología , Proteínas de la Membrana/genética , Ratones , Nucleotidiltransferasas/genética
10.
Am J Kidney Dis ; 57(6): 917-20, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21435763

RESUMEN

Angiosarcoma of the dialysis fistula is a rare occurrence. Of the 8 cases of angiosarcoma of the dialysis fistula reported in the literature, all occurred after kidney transplant and long-term immunosuppression therapy. We report 2 cases of disseminated angiosarcoma of the dialysis fistula in hemodialysis patients without concurrent kidney transplants or immunosuppression. Both patients presented with symptoms of pain and bleeding at the site of the thrombosed fistula. Clinicians should be aware that angiosarcoma of the dialysis fistula can occur in patients without kidney transplants.


Asunto(s)
Derivación Arteriovenosa Quirúrgica/efectos adversos , Hemangiosarcoma/etiología , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Neoplasias Vasculares/etiología , Diagnóstico Diferencial , Hemangiosarcoma/diagnóstico , Humanos , Trasplante de Riñón , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias Vasculares/diagnóstico
11.
Ann Vasc Surg ; 25(3): 386.e1-5, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21269801

RESUMEN

Primary aortoenteric fistula (PAEF) is a potentially fatal condition which poses a considerable diagnostic challenge because of its infrequency and the nonspecific presentation. We report the case of a 61-year old woman who presented to her general practitioner with nonspecific and intermittent rectal bleeding, hematemesis, and weight loss. Four days later, she presented to the emergency department with worsening symptoms. The investigations revealed a new small 3.8-cm abdominal aortic aneurysm on computed axial tomography (CT), however, no evidence of a fistula was observed either on CT scan or endoscopy. Two days later, she became unstable requiring an emergency laparotomy and was taken to the operation theater for an en bloc resection of a segment of the aorta and duodenum with exclusion of the duodenum with an inline reconstruction of the aorta using a Dacron graft for a PAEF. The published data were reviewed to address the issues of optimal diagnostic methods and management of PAEF.


Asunto(s)
Enfermedades de la Aorta/diagnóstico , Enfermedades de la Aorta/cirugía , Enfermedades Duodenales/diagnóstico , Enfermedades Duodenales/cirugía , Fístula Intestinal/diagnóstico , Fístula Intestinal/cirugía , Fístula Vascular/diagnóstico , Fístula Vascular/cirugía , Procedimientos Quirúrgicos Vasculares , Enfermedades de la Aorta/complicaciones , Aortografía/métodos , Enfermedades Duodenales/complicaciones , Femenino , Hemorragia Gastrointestinal/etiología , Hematemesis/etiología , Humanos , Fístula Intestinal/complicaciones , Persona de Mediana Edad , Recto , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Fístula Vascular/complicaciones , Pérdida de Peso
12.
Diab Vasc Dis Res ; 17(3): 1479164120928868, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32538155

RESUMEN

PURPOSE OF STUDY: To investigate toe systolic blood pressure and/or toe-brachial pressure index in predicting healing post minor diabetic foot amputations. KEY METHODS: A systematic search of EMBASE and PubMed (including Medline and The Cochrane Library) was conducted from database inception to 9 March 2020. Two authors independently reviewed and selected relevant studies. Quality was assessed with a modified Critical Appraisal Skill Programme checklist. MAIN RESULTS: Ten studies met the inclusion criteria. Nine studies investigating toe systolic blood pressure reported healing occurred at mean toe systolic blood pressure values ⩾30 mmHg, ranging between 30 and 83.6 mmHg. The meta-analysis (four studies) found toe systolic blood pressure <30 mmHg had 2.09 times the relative risk of non-healing post amputation, compared to toe systolic blood pressure ⩾30 mmHg (relative risk = 2.09, 95% confidence interval: 1.37-3.20, p = 0.001). Two studies investigating toe-brachial pressure index report successful healing where toe-brachial pressure index >0.2, with one study reporting a higher value of 0.8. MAIN CONCLUSIONS: Successful post-amputation healing outcomes were reported at mean toe systolic blood pressure ⩾30 mmHg, and the results varied considerably between the studies. Further research should identify whether variables, including amputation level, method of wound closure and length of post-operative follow-up periods, affect the values of toe systolic blood pressure and toe-brachial pressure index observed in this review.


Asunto(s)
Amputación Quirúrgica , Índice Tobillo Braquial , Presión Sanguínea , Pie Diabético/cirugía , Dedos del Pie/irrigación sanguínea , Dedos del Pie/cirugía , Cicatrización de Heridas , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica/efectos adversos , Pie Diabético/diagnóstico , Pie Diabético/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Flujo Sanguíneo Regional , Factores de Riesgo , Resultado del Tratamiento
13.
JCI Insight ; 5(9)2020 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-32376795

RESUMEN

BACKGROUNDObesity has been associated with attenuated vaccine responses and an increased risk of contracting pneumococcal pneumonia, but no study to our knowledge has assessed the impact of obesity and genetics on 23-valent pneumococcal vaccine (PPSV23) efficacy. We assessed the relationship of obesity (primary analysis) and stimulator of interferon genes (STING1) genotype (secondary analysis) on PPSV23 efficacy.METHODSNonobese (BMI 22-25 kg/m2) and obese participants (BMI ≥30 kg/m2) were given a single dose of PPSV23. Blood was drawn immediately prior to and 4-6 weeks after vaccination. Serum samples were used to assess PPSV23-specific antibodies. STING1 genotypes were identified using PCR on DNA extracted from peripheral blood samples.RESULTSForty-six participants were categorized as nonobese (n = 23; 56.5% women; mean BMI 23.3 kg/m2) or obese (n = 23; 65.2% women; mean BMI 36.3 kg/m2). Obese participants had an elevated fold change in vaccine-specific responses compared with nonobese participants (P < 0.0001). The WT STING1 group (R232/R232) had a significantly higher PPSV23 response than individuals with a single copy of HAQ-STING1 regardless of BMI (P = 0.0025). When WT was assessed alone, obese participants had a higher fold serotype-specific response compared with nonobese participants (P < 0.0001), but no difference was observed between obese and nonobese individuals with 1 HAQ allele (P = 0.693).CONCLUSIONSThese observations demonstrate a positive association between obesity and PPSV23 efficacy specifically in participants with the WT STING1 genotype.TRIAL REGISTRATIONClinicalTrials.gov NCT02471014.FUNDINGThis research was supported by the NIH and the University of Florida MD-PhD Training Program.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Proteínas de la Membrana , Obesidad/inmunología , Infecciones Neumocócicas , Vacunas Neumococicas/administración & dosificación , Adolescente , Adulto , Femenino , Humanos , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Adulto Joven
14.
J Clin Transl Sci ; 3(6): 316-324, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31827905

RESUMEN

INTRODUCTION: MD-PhD training programs train physician-scientists to pursue careers involving both clinical care and research, but decreasing numbers of physician-scientists stay engaged in clinical research. We sought to identify current clinical research training methods utilized by MD-PhD programs and to assess how effective they are in promoting self-efficacy for clinical research. METHODS: The US MD-PhD students were surveyed in April-May 2018. Students identified the clinical research training methods they participated in, and self-efficacy in clinical research was determined using a modified 12-item Clinical Research Appraisal Inventory. RESULTS: Responses were received from 61 of 108 MD-PhD institutions. Responses were obtained from 647 MD-PhD students in all years of training. The primary methods of clinical research training included no clinical research training, and various combinations of didactics, mentored clinical research, and a clinical research practicum. Students with didactics plus mentored clinical research had similar self-efficacy as those with didactics plus clinical research practicum. Training activities that differentiated students who did and did not have the clinical research practicum experience and were associated with higher self-efficacy included exposure to Institutional Review Boards and participation in human subject recruitment. CONCLUSIONS: A clinical research practicum was found to be an effective option for MD-PhD students conducting basic science research to gain experience in clinical research skills. Clinical research self-efficacy was correlated with the amount of clinical research training and specific clinical research tasks, which may inform curriculum development for a variety of clinical and translational research training programs, for example, MD-PhD, TL1, and KL2.

15.
ACS Nano ; 13(12): 13884-13898, 2019 12 24.
Artículo en Inglés | MEDLINE | ID: mdl-31730332

RESUMEN

Cancer vaccines initiate antitumor responses in a subset of patients, but the lack of clinically meaningful biomarkers to predict treatment response limits their development. Here, we design multifunctional RNA-loaded magnetic liposomes to initiate potent antitumor immunity and function as an early biomarker of treatment response. These particles activate dendritic cells (DCs) more effectively than electroporation, leading to superior inhibition of tumor growth in treatment models. Inclusion of iron oxide enhances DC transfection and enables tracking of DC migration with magnetic resonance imaging (MRI). We show that T2*-weighted MRI intensity in lymph nodes is a strong correlation of DC trafficking and is an early predictor of antitumor response. In preclinical tumor models, MRI-predicted "responders" identified 2 days after vaccination had significantly smaller tumors 2-5 weeks after treatment and lived 73% longer than MRI-predicted "nonresponders". These studies therefore provide a simple, scalable nanoparticle formulation to generate robust antitumor immune responses and predict individual treatment outcome with MRI.


Asunto(s)
Antineoplásicos/farmacología , Células Dendríticas/metabolismo , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/química , Animales , Biomarcadores de Tumor/metabolismo , Vacunas contra el Cáncer/inmunología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Rastreo Celular , Células Dendríticas/efectos de los fármacos , Electroporación , Compuestos Férricos/química , Nanopartículas de Magnetita/ultraestructura , Ratones Endogámicos C57BL , Transfección
16.
Nat Commun ; 10(1): 3029, 2019 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-31292444

RESUMEN

With improving biofabrication technology, 3D bioprinted constructs increasingly resemble real tissues. However, the fundamental principles describing how cell-generated forces within these constructs drive deformations, mechanical instabilities, and structural failures have not been established, even for basic biofabricated building blocks. Here we investigate mechanical behaviours of 3D printed microbeams made from living cells and extracellular matrix, bioprinting these simple structural elements into a 3D culture medium made from packed microgels, creating a mechanically controlled environment that allows the beams to evolve under cell-generated forces. By varying the properties of the beams and the surrounding microgel medium, we explore the mechanical behaviours exhibited by these structures. We observe buckling, axial contraction, failure, and total static stability, and we develop mechanical models of cell-ECM microbeam mechanics. We envision these models and their generalizations to other fundamental 3D shapes to facilitate the predictable design of biofabricated structures using simple building blocks in the future.


Asunto(s)
Bioimpresión/métodos , Técnicas de Cultivo de Célula/métodos , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Resinas Acrílicas/química , Animales , Materiales Biocompatibles , Línea Celular Tumoral , Matriz Extracelular , Geles/química , Ensayo de Materiales , Metacrilatos/química , Ratones , Células 3T3 NIH
17.
Diab Vasc Dis Res ; 15(5): 396-401, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29923420

RESUMEN

BACKGROUND: Continuous-wave Doppler is frequently used for detecting peripheral arterial disease in patients with diabetes; however, there is limited evidence investigating diagnostic accuracy. This study aimed to determine sensitivity and specificity of continuous-wave Doppler for detecting peripheral arterial disease in populations with, and without, diabetes and to investigate the influence of disease severity on sensitivity of continuous-wave Doppler for detecting peripheral arterial disease. RESULTS: Data from 396 participants were included. Using colour Duplex ultrasound as reference standard (N=66), printed continuous-wave Doppler waveform analysis sensitivity was 81.75% (95% confidence interval: 76.75 to 85.88) and specificity 89.34% (95% confidence interval: 82.62 to 93.67). Printed continuous-wave Doppler waveform analysis sensitivity for peripheral arterial disease was comparable to sensitivity calculated using angiography as the reference standard (81.67%; 95% confidence interval: 69.56 to 90.48). Sensitivity and specificity were unaffected by diabetes diagnosis (n = 176), sensitivity 82.76% (95% confidence interval: 74.86 to 88.55), and specificity 88.33% (95% confidence interval: 77.82 to 94.23). CONCLUSION: Continuous-wave Doppler is a fair assessment tool for peripheral arterial disease in a community-based sample with suspected peripheral arterial disease. Diagnostic accuracy of continuous-wave Doppler for peripheral arterial disease is unaffected by the presence of diabetes.


Asunto(s)
Diabetes Mellitus , Enfermedad Arterial Periférica/diagnóstico por imagen , Ultrasonografía Doppler , Adulto , Anciano , Anciano de 80 o más Años , Angiografía , Estudios Transversales , Diabetes Mellitus/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Ultrasonografía Doppler en Color
18.
J Foot Ankle Res ; 10: 58, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29270232

RESUMEN

BACKGROUND: The resting systolic toe pressure (TP) is a measure of small arterial function in the periphery. TP is used in addition to the ankle-brachial index when screening for peripheral arterial disease (PAD) of the lower limb in those with diabetes, particularly in the presence of lower limb medial arterial calcification. It may be used as an adjunct assessment of lower limb vascular function and as a predictor of wound healing. The aim of this study was to determine the diagnostic accuracy of TP for detecting PAD in people with and without diabetes. METHODS: This was a retrospective case-control study. Two researchers extracted information from consecutive patient records, including TP measurements, colour Duplex ultrasound results, demographic information, and medical history. Measures of diagnostic accuracy were determined by receiver operating curve (ROC) analysis, and calculation of sensitivity, specificity, and positive and negative likelihood ratios. RESULTS: Three hundred and nintey-four participants with suspected PAD were included. In the diabetes group (n = 176), ROC analysis of TP for detecting PAD was 0.78 (95%CI: 0.69 to 0.84). In the control group (n = 218), the ROC of TP was 0.73 (95%CI: 0.70 to 0.80). TP had highest sensitivity when anatomical distribution of disease was both proximal and distal (diabetes group: 79.49%, the control group: 82.61%). TP yielded highest sensitivity in mild disease (50-75% stenosis) in diabetes group, (81.82%) and moderate disease (>75% stenosis) in control group (80.77%). CONCLUSIONS: Our findings indicate that TPs are useful to assist in diagnosing PAD in clinical practice, however, results should be interpreted with caution due to the small probability of PAD being present with a negative test.


Asunto(s)
Determinación de la Presión Sanguínea/métodos , Angiopatías Diabéticas/diagnóstico , Enfermedad Arterial Periférica/diagnóstico , Anciano , Anciano de 80 o más Años , Presión Sanguínea/fisiología , Estudios de Casos y Controles , Estudios Transversales , Diabetes Mellitus/fisiopatología , Femenino , Humanos , Funciones de Verosimilitud , Masculino , Persona de Mediana Edad , Curva ROC , Descanso/fisiología , Estudios Retrospectivos , Sensibilidad y Especificidad , Dedos del Pie/fisiopatología , Ultrasonografía Doppler Dúplex , Calcificación Vascular/diagnóstico
19.
Asian J Surg ; 26(3): 159-62, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12925291

RESUMEN

BACKGROUND: Early and accurate diagnosis of post-surgical deep vein thrombosis (DVT) can be difficult and time-consuming, even with duplex ultrasonography. Portable continuous-wave Doppler ultrasonography may be useful in screening patients for postoperative DVT. Further confirmation of Doppler-positive cases by duplex ultrasound might then be more cost-effective. METHODS: All major post-surgical patients from the departments of general surgery, orthopaedic surgery and colorectal surgery were screened on the third postoperative day for DVT by assessing the quality of the flow signal ("whoosh") obtained by placing the probe over the femoral vein and subsequently over the popliteal vein, both with a distal squeeze, as well as assessment of phasic flow with respiration. An absent or attenuated "whoosh" was judged to be suspicious for DVT and required formal duplex ultrasonography. The first 800 consecutive patients were studied to determine the sensitivity, specificity and accuracy of portable Doppler ultrasonography for DVT screening. RESULTS: Twenty-four cases of DVT were diagnosed, comprising seven cases in the proximal veins and 17 cases in the calf veins. The sensitivity of Doppler ultrasonography was 12.5% and the specificity was 96.8%. The positive and negative predictive values were 10.7% and 97.3%, respectively. CONCLUSIONS: Portable Doppler ultrasonography does not have adequate accuracy to be used as a quick screening tool for DVT.


Asunto(s)
Complicaciones Posoperatorias/diagnóstico por imagen , Ultrasonografía Doppler/métodos , Trombosis de la Vena/diagnóstico por imagen , Estudios de Cohortes , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Monitoreo Fisiológico/métodos , Periodo Posoperatorio , Medición de Riesgo , Sensibilidad y Especificidad , Ultrasonografía Doppler/estadística & datos numéricos
20.
Singapore Med J ; 54(5): 271-4, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23716153

RESUMEN

INTRODUCTION: The gold standard for evaluation of the lower extremity arterial tree is catheter angiography. Duplex arterial-occlusive imaging or duplex ultrasonography arteriography, a noninvasive technique, is used as the first-line investigation in patients with peripheral vascular disease at our centre. Based on the results of duplex imaging, patients who require angiographic intervention then proceed with simultaneous catheter arteriography and intervention. This study aimed to compare the results of duplex imaging alone as the first-line investigation against the eventual results of catheter angiography, and to assess the impact of the former on patients' clinical outcomes. METHODS: All cases involving patients who underwent duplex imaging followed by angiographic intervention, from May 2008 to February 2009, were discussed at weekly interdisciplinary meetings. Only patients who underwent lower limb imaging were included in the study. Those who were involved in grafts and stent surveillance studies, as well as those with incomplete duplex images were excluded. RESULTS: During the study period, 113 duplex imaging studies of the lower limb followed by percutaneous transluminal angioplasty were performed at our hospital for peripheral vascular disease. The iliac artery was visualised in 40 images, but could not be visualised in 73 images. There was a potential change in management in three cases due to radiological differences between the duplex images and angiography films. CONCLUSION: In our series, duplex imaging was found to be accurate enough to guide initial clinical management of patients with peripheral vascular disease. This modality is the preferred first-line investigation for such patients at our centre.


Asunto(s)
Angiografía/métodos , Pierna/diagnóstico por imagen , Enfermedades Vasculares Periféricas/diagnóstico por imagen , Enfermedades Vasculares Periféricas/diagnóstico , Ultrasonografía Doppler Dúplex/métodos , Ultrasonografía/métodos , Angioplastia/métodos , Arteriopatías Oclusivas/diagnóstico , Arteriopatías Oclusivas/diagnóstico por imagen , Humanos , Pierna/irrigación sanguínea , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados
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