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1.
J Microsc ; 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37727897

RESUMO

The 'Bridging Imaging Users to Imaging Analysis' survey was conducted in 2022 by the Center for Open Bioimage Analysis (COBA), BioImaging North America (BINA) and the Royal Microscopical Society Data Analysis in Imaging Section (RMS DAIM) to understand the needs of the imaging community. Through multichoice and open-ended questions, the survey inquired about demographics, image analysis experiences, future needs and suggestions on the role of tool developers and users. Participants of the survey were from diverse roles and domains of the life and physical sciences. To our knowledge, this is the first attempt to survey cross-community to bridge knowledge gaps between physical and life sciences imaging. Survey results indicate that respondents' overarching needs are documentation, detailed tutorials on the usage of image analysis tools, user-friendly intuitive software, and better solutions for segmentation, ideally in a format tailored to their specific use cases. The tool creators suggested the users familiarise themselves with the fundamentals of image analysis, provide constant feedback and report the issues faced during image analysis while the users would like more documentation and an emphasis on tool friendliness. Regardless of the computational experience, there is a strong preference for 'written tutorials' to acquire knowledge on image analysis. We also observed that the interest in having 'office hours' to get an expert opinion on their image analysis methods has increased over the years. The results also showed less-than-expected usage of online discussion forums in the imaging community for solving image analysis problems. Surprisingly, we also observed a decreased interest among the survey respondents in deep/machine learning despite the increasing adoption of artificial intelligence in biology. In addition, the community suggests the need for a common repository for the available image analysis tools and their applications. The opinions and suggestions of the community, released here in full, will help the image analysis tool creation and education communities to design and deliver the resources accordingly.

2.
J Ultrasound Med ; 41(8): 1993-2002, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34792209

RESUMO

OBJECTIVES: Breast lymphedema has supplanted upper extremity lymphedema as a common and debilitating sequela of breast cancer treatment, but has no objective measurement. We assessed the utility of ultrasound-measured difference in dermal thickness between affected and unaffected breasts as a measure of breast lymphedema. We associated this measure with patient characteristics, treatment parameters, and patient-reported impact on quality of life. METHODS: We enrolled 30 invasive breast carcinoma patients treated with breast-conserving surgery, sentinel lymph node biopsy, and radiotherapy, and 10 control patients evaluated for benign breast conditions without prior breast surgery or radiotherapy. Patient and treatment variables were ascertained from medical records and radiotherapy instruments. Impacts on quality of life were measured with a modified Disability of the Arm, Shoulder, and Hand questionnaire. We characterized breast lymphedema by calculating the difference in ultrasound-measured dermal thickness between affected and unaffected breasts. Associations with patient characteristics, treatment, and quality of life were quantified with log-binomial regression models. RESULTS: Breast lymphedema was defined as a dermal thickness difference of >0.3 mm. Nineteen patients in the invasive group (63%) had breast lymphedema by this definition. We observed positive associations between ultrasound-defined breast lymphedema and surgical factors (size of primary tumor, number of lymph nodes removed), radiotherapy factors (breast volume irradiated, receipt of radiation boost), and patient-reported outcomes (sleep quality and overall confidence). CONCLUSIONS: Difference in dermal thickness is an easy and inexpensive measurement for quantifying breast lymphedema, and correlates with treatment parameters and patient-reported impacts on quality of life.


Assuntos
Neoplasias da Mama , Linfedema , Braço , Axila/patologia , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Linfedema/diagnóstico por imagem , Linfedema/etiologia , Qualidade de Vida , Biópsia de Linfonodo Sentinela/efeitos adversos
3.
Clin Sci (Lond) ; 135(24): 2729-2748, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34918742

RESUMO

Low-grade inflammation is often an underlying cause of several chronic diseases such as asthma, obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). Defining the mediators of such chronic low-grade inflammation often appears dependent on which disease is being investigated. However, downstream systemic inflammatory cytokine responses in these diseases often overlap, noting there is no doubt more than one factor at play to heighten the inflammatory response. Furthermore, it is increasingly believed that diet and an altered gut microbiota may play an important role in the pathology of such diverse diseases. More specifically, the inflammatory mediator endotoxin, which is a complex lipopolysaccharide (LPS) derived from the outer membrane cell wall of Gram-negative bacteria and is abundant within the gut microbiota, and may play a direct role alongside inhaled allergens in eliciting an inflammatory response in asthma. Endotoxin has immunogenic effects and is sufficiently microscopic to traverse the gut mucosa and enter the systemic circulation to act as a mediator of chronic low-grade inflammation in disease. Whilst the role of endotoxin has been considered in conditions of obesity, cardiovascular disease and T2DM, endotoxin as an inflammatory trigger in asthma is less well understood. This review has sought to examine the current evidence for the role of endotoxin in asthma, and whether the gut microbiota could be a dietary target to improve disease management. This may expand our understanding of endotoxin as a mediator of further low-grade inflammatory diseases, and how endotoxin may represent yet another insult to add to injury.


Assuntos
Asma/etiologia , Endotoxinas , Inflamação/fisiopatologia , Adipocinas , Asma/fisiopatologia , Dieta/efeitos adversos , Microbioma Gastrointestinal , Humanos , Obesidade
4.
Methods ; 173: 3-15, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31176770

RESUMO

Quantification and modelling of curvilinear structures in 2D and 3D images is a common challenge in a wide range of biomedical applications. Image enhancement is a crucial pre-processing step for curvilinear structure quantification. Many of the existing state-of-the-art enhancement approaches still suffer from contrast variations and noise. In this paper, we propose to address such problems via the use of a multiscale image processing approach, called Multiscale Top-Hat Tensor (MTHT). MTHT produces a better quality enhancement of curvilinear structures in low contrast and noisy images compared with other approaches in a range of 2D and 3D biomedical images. The proposed approach combines multiscale morphological filtering with a local tensor representation of curvilinear structure. The MTHT approach is validated on 2D and 3D synthetic and real images, and is also compared to the state-of-the-art curvilinear structure enhancement approaches. The obtained results demonstrate that the proposed approach provides high-quality curvilinear structure enhancement, allowing high accuracy segmentation and quantification in a wide range of 2D and 3D image datasets.


Assuntos
Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Algoritmos , Humanos
5.
Surg Innov ; 28(5): 600-610, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33745371

RESUMO

Background: Medical devices are becoming more complex, and doctors need to learn quickly how to use new medical tools. However, it is challenging to objectively assess the fundamental laparoscopic surgical skill level and determine skill readiness for advancement. There is a lack of objective models to compare performance between medical trainees and experienced doctors. Methods: This article discusses the use of similarity network models for individual tasks and a combination of tasks to show the level of similarity between residents and medical students while performing each task and their overall laparoscopic surgical skill level using a medical device (eg laparoscopic instruments). When a medical student is connected to most residents, that student is competent to the next training level. Performance of sixteen participants (5 residents and 11 students) while performing 3 tasks in 3 different training schedules is used in this study. Results: The promising result shows the general positive progression of students over 4 training sessions. Our results also indicate that students with different training schedules have different performance levels. Students' progress in performing a task is quicker if the training sessions are held more closely compared to when the training sessions are far apart in time. Conclusions: This study provides a graph-based framework for evaluating new learners' performance on medical devices and their readiness for advancement. This similarity network method could be used to classify students' performance using similarity thresholds, facilitating decision-making related to training and progression through curricula.


Assuntos
Laparoscopia , Estudantes de Medicina , Competência Clínica , Currículo , Humanos , Projetos Piloto
6.
J Exp Biol ; 223(Pt 12)2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32591339

RESUMO

The human foot serves numerous functional roles during walking, including shock absorption and energy return. Here, we investigated walking with added mass to determine how the foot would alter its mechanical work production in response to a greater force demand. Twenty-one healthy young adults walked with varying levels of added body mass: 0%, +15% and +30% (relative to their body mass). We quantified mechanical work performed by the foot using a unified deformable segment analysis and a multi-segment foot model. We found that walking with added mass tended to magnify certain features of the foot's functions. Magnitudes of both positive and negative mechanical work, during stance in the foot, increased when walking with added mass. Yet, the foot preserved similar amounts of net negative work, indicating that the foot dissipates energy overall. Furthermore, walking with added mass increased the foot's negative work during early stance phase, highlighting the foot's role as a shock-absorber. During mid to late stance, the foot produced greater positive work when walking with added mass, which coincided with greater work from the structures spanning the midtarsal joint (i.e. arch). While this study captured the overall behavior of the foot when walking with varying force demands, future studies are needed to further determine the relative contribution of active muscles and elastic tissues to the foot's overall energy.


Assuntos
, Caminhada , Fenômenos Biomecânicos , Marcha , Humanos , Adulto Jovem
7.
Surg Innov ; 25(1): 81-87, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29115184

RESUMO

Providing computer-based laparoscopic surgical training has several advantages that enhance the training process. Self-evaluation and real-time performance feedback are 2 of these advantages, which avoid dependency of trainees on expert feedback. The goal of this study was to investigate the use of a visual time indicator as real-time feedback correlated with the laparoscopic surgical training. Twenty novices participated in this study working with (and without) different presentations of time indicators. They performed a standard peg transfer task, and their completion times and muscle activity were recorded and compared. Also of interest was whether the use of this type of feedback induced any side effect in terms of motivation or muscle fatigue. RESULTS: Of the 20 participants, 15 (75%) preferred using a time indicator in the training process rather than having no feedback. However, time to task completion showed no significant difference in performance with the time indicator; furthermore, no significant differences in muscle activity or muscle fatigue were detected with/without time feedback. CONCLUSION: The absence of significant difference between task performance with/without time feedback shows that using visual real-time feedback can be included in surgical training based on user preference. Trainees may benefit from this type of feedback in the form of increased motivation. The extent to which this can influence training frequency leading to performance improvement is a question for further study.


Assuntos
Instrução por Computador , Laparoscopia/educação , Realidade Virtual , Competência Clínica , Retroalimentação , Feminino , Humanos , Masculino , Inquéritos e Questionários
8.
Surg Innov ; 25(4): 364-373, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29909731

RESUMO

Natural orifice transluminal endoscopic surgery (NOTES) has gained attention as a revolutionary technique with its potential advantages in eliminating skin incisions, shortening recovery time, and decreasing postoperative complications; however, its practical application is still constrained by the complexity of navigation through the surgical field and paucity of available instruments. Current progress on NOTES focuses on designing flexible articulated robots or fully inserted bimanual robots to address the limitations. However, the lack of multitasking tools, trade-offs between size and power, and lack of sufficient surgical force are too often neglected. The authors designed a bimanual robot with a multifunctional manipulator, which can realize on-site instrument-change according to surgeon needs. An articulated drive mechanism with 2 independent curvature sections was designed to deliver the robot to the surgical site. A corresponding reconfiguration operation sequence was formulated to ease insertion and thereby decrease the design trade-off between size and power. This article presents 3 benchtop and animal tests to evaluate the robotic surgery approach and demonstrate the effectiveness of the robot.


Assuntos
Cirurgia Endoscópica por Orifício Natural/instrumentação , Procedimentos Cirúrgicos Robóticos/instrumentação , Animais , Galinhas , Desenho de Equipamento , Modelos Biológicos , Cirurgia Endoscópica por Orifício Natural/métodos , Procedimentos Cirúrgicos Robóticos/métodos
9.
J Biomech Eng ; 139(8)2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28462423

RESUMO

We have proposed a long-term, noninvasive, nonrestrictive method of delivering and implanting a biosensor within the body via a swallowable implantation capsule robot (ICR). The design and preliminary validation of the ICR's primary subsystem-the sensor deployment system-is discussed and evidence is provided for major design choices. The purpose of the sensor deployment system is to adhere a small biosensor to the mucosa of the intestine long-term, and the modality was inspired by tapeworms and other organisms that employ a strategy of mechanical adhesion to soft tissue via the combined use of hooks or needles and suckers. Testing was performed to refine the design of the suction and needle attachment as well as the sensor ejection features of the ICR. An experiment was conducted in which needle sharpness, needle length, and vacuum volume were varied, and no statistically significant difference was observed. Finally, preliminary testing, coupled with prior work within a live porcine model, provided evidence that this is a promising approach for implanting a biosensor within the small intestine.


Assuntos
Técnicas Biossensoriais/instrumentação , Próteses e Implantes , Robótica/instrumentação , Animais , Cápsulas , Desenho de Equipamento , Suínos
10.
Am J Physiol Cell Physiol ; 309(3): C179-89, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25972452

RESUMO

Prolonged vasoconstrictor-stimulated phospholipase C activity can induce arterial constriction, hypertension, and smooth muscle hypertrophy/hyperplasia. Arrestin proteins are recruited by agonist-occupied G protein-coupled receptors to terminate signaling and counteract changes in vascular tone. Here we determine whether the development of hypertension affects arrestin expression in resistance arteries and how such changes alter arterial contractile signaling and function. Arrestin2/3 expression was increased in mesenteric arteries of 12-wk-old spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto (WKY) controls, while no differences in arrestin expression were observed between 6-wk-old SHR and WKY animals. In mesenteric artery myography experiments, high extracellular K(+)-stimulated contractions were increased in both 6- and 12-wk-old SHR animals. Concentration-response experiments for uridine 5'-triphosphate (UTP) acting through P2Y receptors displayed a leftward shift in 12-wk, but not 6-wk-old animals. Desensitization of UTP-stimulated vessel contractions was increased in 12-wk-old (but not 6-wk-old) SHR animals. Dual IP3/Ca(2+) imaging in mesenteric arterial cells showed that desensitization of UTP and endothelin-1 (ET1) responses was enhanced in 12-wk-old (but not 6-wk-old) SHR compared with WKY rats. siRNA-mediated depletion of arrestin2 for UTP and arrestin3 for ET1, reversed the desensitization of PLC signaling. In conclusion, arrestin2 and 3 expression is elevated in resistance arteries during the emergence of the early hypertensive phenotype, which underlies an enhanced ability to desensitize vasoconstrictor signaling and vessel contraction. Such regulatory changes may act to compensate for increased vasoconstrictor-induced vessel contraction.


Assuntos
Arrestinas/fisiologia , Hipertensão/metabolismo , Vasoconstrição/fisiologia , Animais , Relação Dose-Resposta a Droga , Hipertensão/patologia , Masculino , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/patologia , Técnicas de Cultura de Órgãos , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia , beta-Arrestinas
11.
Breast J ; 21(4): 387-94, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25919123

RESUMO

There is a paucity of data regarding factors affecting enrollment onto radiation oncology clinical trials. The purpose of this study was to determine patients and tumor characteristics that influenced enrollment of breast cancer patients onto hypofractionated breast radiotherapy trials (HBRTs) at a single institution. In this retrospective cohort study, patients enrolled on HBRTs at the Rutgers Cancer Institute of New Jersey (n = 132) were compared with a cohort of breast cancer patients eligible for, but not enrolled onto HBRTs treated during the same time period (n = 132). Charts were retrospectively reviewed to determine patients' demographics, clinico-pathologic factors, and treatment characteristics. Statistical analysis was performed to analyze variables affecting enrollment onto HBRTs between the two groups. Over a 42-month time period, 132 patients treated on HBRTs received 2,475-4,995 cGy over 3 to 15 fractions. When compared with patients treated off trial, there was no statistically significant effect of age, family history, lymph node positivity, tumor grade, estrogen or Her-2 receptor status, use of chemotherapy or hormones, use of brachytherapy, or the site of initial consultation on HBRT enrollment. Non-White women were less likely to enroll in HBRT's when compared with White women (25.7% versus 40.1%, p = 0.0129), though this was found to be a nonsignificant trend when taking stage into consideration on multivariate analysis (OR for lower T-stage: 0.281, p = 0.003, OR 1.839 for white race, p = 0.076). Consistent with previous studies, non-White women were less likely to enroll in HBRTs than White women. However, disease stage accounted for these racial disparities. Further studies must be performed to determine if race is an independent factor determining radiation oncology clinical trial enrollment.


Assuntos
Neoplasias da Mama/radioterapia , Ensaios Clínicos como Assunto , Etnicidade/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Participação do Paciente/estatística & dados numéricos , Hipofracionamento da Dose de Radiação , Adulto , Neoplasias da Mama/patologia , Estudos de Coortes , Tomada de Decisões , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia/métodos
14.
Respir Res ; 14: 77, 2013 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-23890215

RESUMO

BACKGROUND: Meta-analyses of genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) spanning the 5-hydroxytryptamine receptor 4 (5-HT4R) gene (HTR4) associated with lung function. The aims of this study were to i) investigate the expression profile of HTR4 in adult and fetal lung tissue and cultured airway cells, ii) further define HTR4 gene structure and iii) explore the potential functional implications of key SNPs using a bioinformatic approach. METHODS: Following reverse transcription (RT)-PCR in human brain, 5' rapid amplification of cDNA ends (5' RACE) was used to examine the exonic structure of HTR4 at the 5' end. Quantitative (Q)-PCR was used to quantify HTR4 mRNA expression in total RNA from cultured airway cells and whole lung tissue. Publically available gene microarray data on fetal samples of estimated gestational age 7-22 weeks were mined for HTR4 expression. Immunohistochemistry (IHC; in adult and fetal lung tissue) and a radioligand binding assay (in cultured airway cells) were used to analyze 5-HT4R protein expression. RESULTS: IHC in adult lung, irrespective of the presence of chronic obstructive pulmonary disease (COPD), suggested low level expression of 5-HT4R protein, which was most prominent in alveolar pneumocytes. There was evidence of differential 5-HT4R protein levels during gestation in fetal lung, which was also evident in gene expression microarray data. HTR4 mRNA expression, assessed by Q-PCR, was <0.5% relative to brain in total adult lung tissue and in human airway smooth muscle (HASM) and bronchial epithelial cells (HBEC) derived from adult donors. Radioligand binding experiments also indicated that HBEC and HASM cells did not express a significant 5-HT4R population. 5' RACE in brain identified a novel N-terminal variant, containing an extended N-terminal sequence. The functional significance of key HTR4 SNPs was investigated using the encyclopedia of DNA elements consortium (ENCODE) dataset. These analyses identified multiple alterations in regulatory motifs for transcription factors implicated in lung development, including Foxp1. CONCLUSIONS: Taken together, these data suggest a role for HTR4 in lung development, which may at least in part explain the genetic association with lung function.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/genética , Pulmão/embriologia , Pulmão/fisiologia , Receptores de Serotonina/genética , Feminino , Humanos , Masculino
15.
Surg Endosc ; 27(9): 3474-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23572222

RESUMO

BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) has many potential advantages over other minimally invasive surgical techniques, but it presents a number of challenges introduced by the restrictive natural access points. Fully insertable dexterous in vivo robots have been developed that eliminate the spatial restrictions of the entry point, but they also are isolated within the abdomen. A material handling system (MHS) developed to bridge the gap between the in vivo robots and the surgical team promises a number of improvements over other current technologies. METHODS: The MHS was implemented with two different nonsurvival swine models to validate the utility and benefits of the system. The first procedure was attempted transgastrically but proved too difficult because the geometry of the esophagus was prohibitively small. The system was instead inserted via a 50-mm GelPort and tested for robustness. The second procedure used a transvaginal insertion via a custom 25-mm trocar. Throughout both procedures, the practitioners were asked for qualitative feedback regarding the effectiveness of the device and its long-term efficiencies. RESULTS: The MHS was able to deliver a standard surgical staple securely to the peritoneal cavity. The practitioner was able to use the laparoscopic grasper both to insert and to remove the staple from the MHS. The system also proved capable of maintaining insufflation pressure throughout a procedure. It was cycled a total of five times in both the insertion and the retraction directions. Visualization from the MHS camera was poor at times because the lighting on the system was somewhat inadequate. No excessive bleeding or collateral damage to surrounding tissues was observed during the procedure. CONCLUSIONS: This study demonstrated that the MHS is fully capable of achieving payload transport during a NOTES operation. The system is intuitive and easy to use. It dramatically decreases collateral trauma in the natural access point and can advantageously reduce the overall duration of a procedure.


Assuntos
Cirurgia Endoscópica por Orifício Natural/instrumentação , Robótica/instrumentação , Animais , Desenho de Equipamento , Feminino , Modelos Animais , Grampeamento Cirúrgico , Suínos , Vagina
16.
bioRxiv ; 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37333353

RESUMO

The "Bridging Imaging Users to Imaging Analysis" survey was conducted in 2022 by the Center for Open Bioimage Analysis (COBA), Bioimaging North America (BINA), and the Royal Microscopical Society Data Analysis in Imaging Section (RMS DAIM) to understand the needs of the imaging community. Through multi-choice and open-ended questions, the survey inquired about demographics, image analysis experiences, future needs, and suggestions on the role of tool developers and users. Participants of the survey were from diverse roles and domains of the life and physical sciences. To our knowledge, this is the first attempt to survey cross-community to bridge knowledge gaps between physical and life sciences imaging. Survey results indicate that respondents' overarching needs are documentation, detailed tutorials on the usage of image analysis tools, user-friendly intuitive software, and better solutions for segmentation, ideally in a format tailored to their specific use cases. The tool creators suggested the users familiarize themselves with the fundamentals of image analysis, provide constant feedback, and report the issues faced during image analysis while the users would like more documentation and an emphasis on tool friendliness. Regardless of the computational experience, there is a strong preference for 'written tutorials' to acquire knowledge on image analysis. We also observed that the interest in having 'office hours' to get an expert opinion on their image analysis methods has increased over the years. In addition, the community suggests the need for a common repository for the available image analysis tools and their applications. The opinions and suggestions of the community, released here in full, will help the image analysis tool creation and education communities to design and deliver the resources accordingly.

17.
Am J Physiol Cell Physiol ; 302(5): C723-34, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22159081

RESUMO

Overstimulation of endothelin type A (ET(A)) and nucleotide (P2Y) Gα(q)-coupled receptors in vascular smooth muscle causes vasoconstriction, hypertension, and, eventually, hypertrophy and vascular occlusion. G protein-coupled receptor kinases (GRKs) and arrestin proteins are sequentially recruited by agonist-occupied Gα(q)-coupled receptors to terminate phospholipase C signaling, preventing prolonged/inappropriate contractile signaling. However, these proteins also play roles in the regulation of several mitogen-activated protein kinase (MAPK) signaling cascades known to be essential for vascular remodeling. Here we investigated whether different arrestin isoforms regulate endothelin and nucleotide receptor MAPK signaling in rat aortic smooth muscle cells (ASMCs). When intracellular Ca(2+) levels were assessed in isolated ASMCs loaded with Ca(2+)-sensitive dyes, P2Y(2) and ET(A) receptor desensitization was attenuated by selective small-interfering (si)RNA-mediated depletion of G protein-coupled receptor kinase 2 (GRK2). Using similar siRNA techniques, knockdown of arrestin2 prevented P2Y(2) receptor desensitization and enhanced and prolonged p38 and ERK MAPK signals, while arrestin3 depletion was ineffective. Conversely, arrestin3 knockdown prevented ET(A) receptor desensitization and attenuated ET1-stimulated p38 and ERK signals, while arrestin2 depletion had no effect. Using Transwell assays to assess agonist-stimulated ASMC migration, we found that UTP-stimulated migration was markedly attenuated following arrestin2 depletion, while ET1-stimulated migration was attenuated following knockdown of either arrestin. These data highlight a differential arrestin-dependent regulation of ET(A) and P2Y(2) receptor-stimulated MAPK signaling. GRK2 and arrestin expression are essential for agonist-stimulated ASMC migration, which, as a key process in vascular remodeling, highlights the potential roles of GRK2 and arrestin proteins in the progression of vascular disease.


Assuntos
Arrestinas/metabolismo , Hipertensão/metabolismo , Músculo Liso Vascular/metabolismo , Receptor de Endotelina A/metabolismo , Receptores Purinérgicos P2Y2/metabolismo , Animais , Arrestinas/antagonistas & inibidores , Arrestinas/genética , Artérias/metabolismo , Cálcio/análise , Movimento Celular/fisiologia , Fura-2/análogos & derivados , Fura-2/análise , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Técnicas de Silenciamento de Genes , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miócitos de Músculo Liso/química , Miócitos de Músculo Liso/metabolismo , Fosforilação , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais , Fosfolipases Tipo C/metabolismo
18.
Curr Eye Res ; 47(2): 304-311, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34894934

RESUMO

PURPOSE: The lamina cribrosa (LC) is a layer of fenestrated connective tissue tethered to the posterior sclera across the scleral canal in the optic nerve head (ONH). It is located at the interface of intracranial and intraocular compartments and is exposed to intraocular pressure (IOP) anteriorly and intracranial pressure (ICP) or Cerebrospinal fluid (CSF) pressure (CSFP) posteriorly. We hypothesize that the pressure difference across LC will determine LC position and meridional diameter of scleral canal (also called Bruch's membrane opening diameter; BMOD). METHODS: We enrolled 19 human subjects undergoing a medically necessary lumbar puncture (LP) to lower CSFP and 6 anesthetized pigs, whose ICP was increased in 5 mm Hg increments using a lumbar catheter. We imaged ONH using optical coherence tomography and measured IOP and CSFP/ICP at baseline and after each intervention. Radial tomographic ONH scans were analyzed by two independent graders using ImageJ, an open-source software. The following ONH morphological parameters were obtained: BMOD, anterior LC depth and retinal thickness. We modeled effects of acute CSFP/ICP changes on ONH morphological parameters using ANOVA (human study) and generalized linear model (pig study). RESULTS: For 19 human subjects, CSFP ranged from 5 to 42 mm Hg before LP and 2 to 19.4 mm Hg after LP. For the six pigs, baseline ICP ranged from 1.5 to 9 mm Hg and maximum stable ICP ranged from 18 to 40 mm Hg. Our models showed that acute CSFP/ICP changes had no significant effect on ONH morphological parameters in both humans and pigs. CONCLUSION: We conclude that ONH does not show measurable morphological changes in response to acute changes of CSFP/ICP. Proposed mechanisms include compensatory and opposing changes in IOP and CSFP/ICP and nonlinear or nonmonotonic effects of IOP and CSFP/ICP across LC.


Assuntos
Disco Óptico , Animais , Humanos , Pressão Intracraniana/fisiologia , Pressão Intraocular , Suínos , Tomografia de Coerência Óptica , Tonometria Ocular
19.
Adv Radiat Oncol ; 7(5): 100897, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36148379

RESUMO

Cyberattacks on health care facilities are increasing and significantly affecting health care delivery throughout the world. The recent cyberattack on our hospital-based radiation facility exposed vulnerabilities of radiation oncology systems and highlighted the dependence of radiation treatment on integrated and complex radiation planning, delivery and verification systems. After the cyberattack on our health care facility, radiation oncology staff reconstructed patient information, schedules, and radiation plans from existing paper records and physicians developed a system to triage patients requiring immediate transfer of radiation treatment to nearby facilities. Medical physics and hospital information technology collaborated to restore services without access to the system backup or network connectivity. Ultimately, radiation treatments resumed incrementally as systems were restored and rebuilt. The experiences and lessons learned from this response were reviewed. The successes and shortcomings were incorporated into recommendations to provide guidance to other radiation facilities in preparation for a possible cyberattack. Our response and recommendations are intended to serve as a starting point to assist other facilities in cybersecurity preparedness planning. Because there is no one-size-fits-all response, each department should determine its specific vulnerabilities, risks, and available resources to create an individualized plan.

20.
Cancer ; 117(18): 4116-24, 2011 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-21365631

RESUMO

BACKGROUND: Radiation-induced fatigue is a common side effect of breast cancer radiotherapy (RT). This study compares the induction and persistence of radiation-induced fatigue in accelerated partial breast irradiation (APBI), accelerated hypofractionated RT, and standard whole breast RT. METHODS: Eighty patients were treated with a novel, 3-week accelerated regimen with 333 centigrays (cGy) for 15 fractions to 4995 cGy; of these, 45 were treated using APBI, whereas 35 patients were treated using accelerated hypofractionated RT. These patients were matched with patients receiving 200 cGy for 30 fractions using standard whole breast irradiation. Fatigue score, using Common Terminology Criteria for Adverse Events version 4.0, was obtained at 5 time points: consultation before RT, first on-treatment visit, halfway through treatment, last on-treatment visit, and first follow-up. RESULTS: Maximum fatigue and average fatigue since treatment were calculated. Maximum fatigue was 1.5, 2.4, and 2.3, and average fatigue was 0.46, 0.81, and 0.92 for the APBI, accelerated hypofractionated RT, and standard whole breast RT groups, respectively. The accelerated schedules did not have significantly less fatigue than standard whole breast RT at first on-treatment visit. Maximum fatigue in APBI was reduced compared with standard whole breast RT. Accelerated hypofractionated RT had fatigue trajectory similar to standard whole breast RT. Multivariate analysis found that increased age and whole breast treatment are associated with more fatigue. Chemotherapy, hormone therapy, race, and T stage were not significant predictors of maximum fatigue. Results were similar for average fatigue, except that magnitudes were smaller. CONCLUSIONS: Field sizes and age in breast RT were positively associated with maximum radiation-induced fatigue. Accelerated hypofractionated RT and standard whole breast RT had similar fatigue trajectories compared with APBI, which reduced fatigue at all times.


Assuntos
Neoplasias da Mama/radioterapia , Fadiga/etiologia , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Feminino , Humanos , Pessoa de Meia-Idade
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