RESUMO
STUDY OBJECTIVE: The primary objective of this study was to examine the common usage patterns of droperidol in the relatively unrestricted environment of an urban, academic medical center. We focused specifically on the most common use of droperidol in our department: patients with a chief complaint of abdominal pain, nausea, and/or vomiting. METHODS: For this retrospective, observational, single-center study, we extracted records of all administrations of droperidol from August 2019 to August 2020. Patients with a chief complaint of abdominal pain, nausea, or vomiting, or any combination thereof, were included in data analysis. RESULTS: Between April 2019 to August 2020, 830 discrete patient visits involving droperidol administration were identified, comprising 706 patients. The average age was 39 years old with a range of 15 to 80. Seven patients (0.08%) were younger than 18, and 35 (4%) were older than 65. Five hundred sixty-five patients (68%) were female. Droperidol doses ranged from 0.625 mg to 5 mg intravenous (IV), with a median dose of 0.625 mg (interquartile range 0.625-1.25 mg), with 590 patients (71%) receiving a dose of 0.625 mg. Only 19 patients (2.3%) had a documented adverse event. Seven had akathisia or restlessness, 7 had anxiety or agitation, 3 had dystonia or stiffness, 1 had fatigue, and 1 had dizziness. For the entire cohort, there were no cardiac dysrhythmias, syncope, seizures, other major adverse events, or fatalities recorded. CONCLUSION: At one institution, droperidol is being used commonly for the chief complaints of abdominal pain, nausea, and/or vomiting. The preferred dosing is nearly universally below the 2.5 mg IV dose for which the FDA warning applies. Similar to previous studies, identification of adverse events was rare, and no major adverse outcomes such as dysrhythmia or death were identified.
Assuntos
Dor Abdominal , Antieméticos , Droperidol , Serviço Hospitalar de Emergência , Náusea , Vômito , Humanos , Droperidol/administração & dosagem , Droperidol/efeitos adversos , Droperidol/uso terapêutico , Feminino , Masculino , Adulto , Estudos Retrospectivos , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Vômito/induzido quimicamente , Pessoa de Meia-Idade , Dor Abdominal/tratamento farmacológico , Antieméticos/administração & dosagem , Antieméticos/efeitos adversos , Antieméticos/uso terapêutico , Adolescente , Idoso , Adulto Jovem , Idoso de 80 Anos ou maisRESUMO
Immunodeficient mice bearing human immune systems, or "humanized" chimeric mice, are widely used in basic research, along with the preclinical stages of drug development. Nonobese diabetic-severe combined immunodeficiency (NOD-SCID) IL2Rγnull (NSG) mice expressing human stem cell factor, granulocyte-macrophage colony stimulating factor, and interleukin-3 (NSG-SGM3) support robust development of human myeloid cells and T cells but have reduced longevity due to the development of fatal hemophagocytic lymphohistiocytosis (HLH). Here, we describe an optimized protocol for development of human immune chimerism in NSG-SGM3 mice. We demonstrate that efficient human CD45+ reconstitution can be achieved and HLH delayed by engraftment of neonatal NSG-SGM3 with low numbers of human umbilical cord-derived CD34+ hematopoietic stem cells in the absence of preconditioning irradiation.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfo-Histiocitose Hemofagocítica , Camundongos , Humanos , Animais , Recém-Nascido , Linfo-Histiocitose Hemofagocítica/terapia , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Hematopoéticas , Antígenos CD34 , Linfócitos TRESUMO
BACKGROUND: The United States faces a nursing shortage driven by a burnout epidemic among nurses and nursing students. Nursing students are an integral population to fuel the nursing workforce at high risk of burnout and increased rates of perceived stress. OBJECTIVE: The aim of this paper is to describe WellNurse, a holistic, interdisciplinary, multidimensional longitudinal research study that examines evidence-based interventions intended to reduce burnout and increase resilience among graduate and undergraduate nursing students. METHODS: Graduate and undergraduate nursing students matriculated at a large public university in the northeastern United States are eligible to enroll in this ongoing, longitudinal cohort study beginning in March 2021. Participants complete a battery of health measurements twice each semester during the fourth week and the week before final examinations. The measures include the Perceived Stress Scale, the Satisfaction with Life Scale, the Oldenburg Burnout Inventory, the Brief Resilience Scale, and the Pittsburgh Sleep Quality Index. Participants are eligible to enroll in a variety of interventions, including mindfulness-based stress reduction, mindful eating, fitness training, and massage therapy. Those who enroll in specific, targeted interventions complete additional measures designed to target the aim of the intervention. All participants receive a free Fitbit device. Additional environmental changes are being implemented to further promote a culture that supports academic well-being, including recruiting a diverse student population through evidence-based holistic admissions, inclusive teaching design, targeted resilience and stress reduction workshops, and cultural shifts within classrooms and curricula. The study design protocol is registered at Open Science Framework (DOI 10.17605/OSF.IO/NCBPE). RESULTS: The project was funded on January 1, 2022. Data collection started in March 2022. A total of 267 participants have been recruited. Results will be published after each semester starting in December 2023. WellNurse evaluation follows the Rapid Cycle Quality Improvement framework to continuously monitor ongoing project processes, activity outcomes, and progress toward reducing burnout and increasing resilience. Rapid Cycle Quality Improvement promotes the ability to alter WellNurse interventions, examine multiple interventions, and test their effectiveness among the nursing education population to identify the most effective interventions. CONCLUSIONS: Academic nursing organizations must address student burnout risk and increase resilience to produce a future workforce that provides high-quality patient care to a diverse population. Findings from WellNurse will support evidence-based implementations for public baccalaureate and master's nursing programs in the United States. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49020.
RESUMO
Psychiatric and metabolic disorders are highly comorbid and the relationship between these disorders is bidirectional. The mechanisms underlying the association between psychiatric and metabolic disorders are presently unclear, which warrants investigation into the dynamics of the interplay between metabolism, substrate utilization, and energy expenditure in psychiatric populations, and how these constructs compare to those in healthy controls. Indirect calorimetry (IC) methods are a reliable, minimally invasive means for assessing metabolic rate and substrate utilization in humans. This review synthesizes the extant literature on the use of IC on resting metabolism in psychiatric populations to investigate the interaction between psychiatric and metabolic functioning. Consistently, resting energy expenditures and/or substrate utilization values were significantly different between psychiatric and healthy populations in the studies contained in this review. Furthermore, resting energy expenditure values were systematically overestimated when derived from predictive equations, compared to when measured by IC, in psychiatric populations. High heterogeneity between study populations (e.g., differing diagnoses and drug regimens) and methodologies (e.g., differing posture, time of day, and fasting status at measurement) impeded the synthesis of results. Standardized IC protocols would benefit this line of research by enabling meta-analyses, revealing trends within and between different psychiatric disorders.
Assuntos
Metabolismo Energético , Transtornos Mentais , Humanos , Calorimetria Indireta/métodos , Calorimetria , Descanso , Metabolismo BasalRESUMO
With few curative treatments and a global yearly death rate of over 800,000, hepatocellular carcinoma (HCC) desperately needs new therapies. Although wild-type p53 gene therapy has been shown to be safe in HCC patients, it has not shown enough efficacy to merit approval. This work aims to show how p53 can be re-engineered through fusion to the pro-apoptotic BH3 protein Bcl-2 antagonist of cell death (Bad) to improve anti-HCC activity and potentially lead to a novel HCC therapeutic, p53-Bad*. p53-Bad* is a fusion of p53 and Bad, with two mutations, S112A and S136A. We determined mitochondrial localization of p53-Bad* in liver cancer cell lines with varying p53 mutation statuses via fluorescence microscopy. We defined the apoptotic activity of p53-Bad* in four liver cancer cell lines using flow cytometry. To determine the effects of p53-Bad* in vivo, we generated and analyzed transgenic zebrafish expressing hepatocyte-specific p53-Bad*. p53-Bad* localized to the mitochondria regardless of the p53 mutation status and demonstrated superior apoptotic activity over WT p53 in early, middle, and late apoptosis assays. Tumor burden in zebrafish HCC was reduced by p53-Bad* as measured by the liver-to-body mass ratio and histopathology. p53-Bad* induced significant apoptosis in zebrafish HCC as measured by TUNEL staining but did not induce apoptosis in non-HCC fish. p53-Bad* can induce apoptosis in a panel of liver cancer cell lines with varying p53 mutation statuses and induce apoptosis/reduce HCC tumor burden in vivo in zebrafish. p53-Bad* warrants further investigation as a potential new HCC therapeutic.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Peixe-Zebra/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Carga Tumoral , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Terapia Genética , Linhagem Celular TumoralRESUMO
Ischemic preconditioning (IPC) has been reported to augment exercise performance, but there is considerable heterogeneity in the magnitude and frequency of performance improvements. Despite a burgeoning interest in IPC as an ergogenic aid, much is still unknown about the physiological mechanisms that mediate the observed performance enhancing effects. This narrative review collates those physiological responses to IPC reported in the IPC literature and discusses how these responses may contribute to the ergogenic effects of IPC. Specifically, this review discusses documented central and peripheral cardiovascular responses, as well as selected metabolic, neurological, and perceptual effects of IPC that have been reported in the literature.
RESUMO
Aim: Little is known about whether pain can be effectively managed in pregnant women with opioid use disorder (OUD) during delivery hospitalization, particularly those undergoing surgery and taking buprenorphine as medication for OUD (MOUD). To address this question, we compared pain scores and opioid analgesic utilization during delivery hospitalization in women taking their pre-hospital dose of buprenorphine who delivered by cesarean section to matched controls. To inform future research efforts, we also began to explore opioid analgesic utilization and pain scores by type of anesthesia as this variable is often not included in related literature. Methods: Retrospective matched cohort study of 46 women prescribed buprenorphine during pregnancy who delivered by cesarean section during a 7-year period. Results: When compared to matched controls, women taking their pre-hospital dose of buprenorphine undergoing cesarean section utilized more opioid analgesics as measured by morphine milligram equivalents (MME) (mean MME first 48 hours 153.0 mg vs 175.1 mg, respectively, P < .01) but had similar pain scores during delivery hospitalization. There was no difference in MME utilization by maternal dose of buprenorphine though sample sizes were small. Women on buprenorphine who received spinal anesthesia with morphine had mean pain scores that were 1.4 points lower (P = .01) during the first 48 hours than women on buprenorphine receiving other methods of anesthesia. Discussion And Conclusions: Pregnant women taking their pre-hospital dose of buprenorphine throughout their surgical delivery hospitalization were able to achieve pain relief similar to women not on MOUD but had higher MME requirements. Our results add to the emerging body of evidence suggesting that individuals on MOUD can achieve adequate post-surgical pain management without adjusting their pre-hospital dose of buprenorphine. Further research is required to fully understand the optimal buprenorphine dosing regimen during surgical hospitalizations. Our results also provide important preliminary evidence that spinal anesthesia containing opioids can be used effectively in individuals with OUD requiring surgical intervention.
RESUMO
One-dimensional strings of local excitations are a fascinating feature of the physical behavior of strongly correlated topological quantum matter. Here we study strings of local excitations in a classical system of interacting nanomagnets, the Santa Fe Ice geometry of artificial spin ice. We measured the moment configuration of the nanomagnets, both after annealing near the ferromagnetic Curie point and in a thermally dynamic state. While the Santa Fe Ice lattice structure is complex, we demonstrate that its disordered magnetic state is naturally described within a framework of emergent strings. We show experimentally that the string length follows a simple Boltzmann distribution with an energy scale that is associated with the system's magnetic interactions and is consistent with theoretical predictions. The results demonstrate that string descriptions and associated topological characteristics are not unique to quantum models but can also provide a simplifying description of complex classical systems with non-trivial frustration.
RESUMO
Ischemic preconditioning (IPC) has been repeatedly reported to augment maximal exercise performance over a range of exercise durations and modalities. However, an examination of the relevant literature indicates that the reproducibility and robustness of ergogenic responses to this technique are variable, confounding expectations about the magnitude of its effects. Considerable variability among study methodologies may contribute to the equivocal responses to IPC. This review focuses on the wide range of methodologies used in IPC research, and how such variability likely confounds interpretation of the interactions of IPC and exercise. Several avenues are recommended to improve IPC methodological consistency, which should facilitate a future consensus about optimizing the IPC protocol, including due consideration of factors such as: location of the stimulus, the time between treatment and exercise, individualized tourniquet pressures and standardized tourniquet physical characteristics, and the incorporation of proper placebo treatments into future study designs.
RESUMO
BACKGROUND: The conventional type 1 dendritic cell subset (cDC1) is indispensable for tumor immune responses and the efficacy of immune checkpoint inhibitor (ICI) therapies in animal models but little is known about the role of the human CD141+ DC cDC1 equivalent in patients with melanoma. METHODS: We developed a flow cytometry assay to quantify and characterize human blood DC subsets in healthy donors and patients with stage 3 and stage 4 metastatic melanoma. To examine whether harnessing CD141+ DCs could improve responses to ICIs in human melanoma, we developed a humanized mouse model by engrafting immunodeficient NSG-SGM3 mice with human CD34+ hematopoietic stem cells (HSCs) from umbilical cord blood followed by transplantation of a human melanoma cell line and treatment with anti-programmed cell death protein-1 (anti-PD-1). RESULTS: Blood CD141+ DC numbers were significantly reduced in patients with stage 4 melanoma compared with healthy controls. Moreover, CD141+ DCs in patients with melanoma were selectively impaired in their ability to upregulate CD83 expression after stimulation with toll-like receptor 3 (TLR3) and TLR7/8 agonists ex vivo. Although DC numbers did not correlate with responses to anti-PD-1 and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) ICIs, their numbers and capacity to upregulate CD83 declined further during treatment in non-responding patients. Treatment with anti-PD-1 was ineffective at controlling tumor growth in humanized mice but efficacy was enhanced by indirectly expanding and activating DCs in vivo with fms-like tyrosine kinase-3 ligand (Flt3L) and a TLR3 agonist. Moreover, intratumoral injections of CD141+ DCs resulted in reduced tumor growth when combined with anti-PD-1 treatment. CONCLUSIONS: These data illustrate quantitative and qualitative impairments in circulating CD141+ DCs in patients with advanced melanoma and that increasing CD141+ DC number and function is an attractive strategy to enhance immunogenicity and response rates to ICIs.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Células Dendríticas/transplante , Transplante de Células-Tronco Hematopoéticas , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia Adotiva , Melanoma/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/terapia , Trombomodulina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos CD34/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Terapia Combinada , Citocinas/sangue , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Feminino , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Masculino , Melanoma/imunologia , Melanoma/metabolismo , Melanoma/patologia , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Objective: To determine the potential impact of prenatal buprenorphine exposure on head circumference at birth and analyze whether head circumference may be related to maternal buprenorphine dose at delivery, delayed maternal entry into buprenorphine treatment or exposure to a variety of other medications and substances.Methods: A retrospective cohort study was performed of 137 full-term infants exposed to buprenorphine during pregnancy from January 2013 to December 2017. Pearson's correlation was calculated to investigate the potential relationship between head circumference and maternal dose of buprenorphine at delivery. t-tests were conducted to analyze head circumference in relationship to dichotomous variables.Results: Head circumference in infants exposed to buprenorphine during pregnancy was not significantly different from national norms for either male infants (95% CI 28.2-33.5 cm, norm 31.5 cm, and 28.5-34.9 cm, norm 33.1 cm, for the 3rd and 10th percentile, respectively) or female infants (95% CI 28.7-32.8 cm, norm 31.9 cm, and 29.1-34.3, norm 32.8 cm for the 3rd and 10th percentile, respectively). Head circumference was not associated with delayed maternal entry into buprenorphine treatment (t = -1.0715, p = .287) or exposure to psychotropic medications during pregnancy (t = 0.4194, p = .677). There was no relationship between infant head circumference and maternal buprenorphine dose at delivery (r = 0.004, p = .967). Head circumference was not associated with maternal smoking (t = 0.003, p = .998) or exposure to marijuana (t = 0.7277, p = .468), illicit opioids (t = -0.6701, p = .504), illicit amphetamines (t = -0.4062, p = .687) or illicit benzodiazepines (t = -0.6288, p = .535) during pregnancy.Conclusions: Exposure to buprenorphine prenatally does not appear to be associated with reduced head circumference at birth. Head circumference at birth also does not appear related to either maternal buprenorphine dose at delivery or delayed entry into treatment. As previous literature suggests that high dose methadone exposure during pregnancy may be associated with smaller head circumference and that smaller head circumference may be associated with risk of neurocognitive disorders, our results further support the use of buprenorphine as a first line treatment for opioid use disorders during pregnancy.
Assuntos
Buprenorfina , Síndrome de Abstinência Neonatal , Transtornos Relacionados ao Uso de Opioides , Complicações na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Buprenorfina/efeitos adversos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Metadona , Gravidez , Estudos RetrospectivosRESUMO
We evaluated the time course of persistent automatic spreading activation from a mediated list of indirect associates (e.g., meow, day, and basement) that all converged upon a non-presented critical item (CI; e.g., black). Mediated lists were related to CIs through non-presented mediators (e.g., cat, night, and bottom). Three speeded tasks were used to evaluate the time course of semantic activation of the CI: a continuous semantic classification task (concrete/abstract decisions), a naming task (reading words aloud), or a recognition test (old/new memory decisions). Test lists were presented immediately following the mediated lists, and CIs were presented in the first, third, or eighth positions. The results revealed that in both the classification and naming tasks, CI priming was greatest in the first test position and declined across the remaining test positions. Importantly, priming was statistically reliable in the late test positions, providing evidence for long-term semantic priming (i.e., across positions on immediate tasks). False recognition, however, was stable across test positions. Collectively, these patterns suggest that spreading-activation processes decline, consistent with implicit spreading activation, and these processes may contribute to long-term false recognition.
Assuntos
Memória , Semântica , Humanos , Leitura , Reconhecimento PsicológicoRESUMO
BACKGROUND AND PURPOSE: To measure wellness interventions, researchers need valid and reliable tools to measure the concept of wellness. The purpose of this study is to examine the validity and reliability of the Lifestyle Survey instrument. METHODS: Community-dwelling older adults were recruited and asked to evaluate the reliability by engaging in a test retest reliability. Observer agreement was measured by calculating a kappa score for each item. Content validity was evaluated with a focus group session. RESULTS: (n = 56) older adults completed the survey on time one and time two. Of 115 items, 77.39% demonstrated moderate or higher kappa agreement. Focus group respondents identified rewording a few items. CONCLUSION: With refinement, the Lifestyle Survey is a valid and reliable measure of wellness among community-dwelling older adults.
Assuntos
Avaliação Geriátrica/métodos , Avaliação Geriátrica/estatística & dados numéricos , Nível de Saúde , Vida Independente/estatística & dados numéricos , Estilo de Vida , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/normas , Reprodutibilidade dos Testes , Inquéritos e Questionários/normasRESUMO
BACKGROUND: Dendritic cells (DCs) are crucial for the efficacy of cancer vaccines, but current vaccines do not harness the key cDC1 subtype required for effective CD8+ T-cell-mediated tumor immune responses. Vaccine immunogenicity could be enhanced by specific delivery of immunogenic tumor antigens to CD141+ DCs, the human cDC1 equivalent. CD141+ DCs exclusively express the C-type-lectin-like receptor CLEC9A, which is important for the regulation of CD8+ T cell responses. This study developed a new vaccine that harnesses a human anti-CLEC9A antibody to specifically deliver the immunogenic tumor antigen, NY-ESO-1 (New York esophageal squamous cell carcinoma 1), to human CD141+ DCs. The ability of the CLEC9A-NY-ESO-1 antibody to activate NY-ESO-1-specific naïve and memory CD8+ T cells was examined and compared with a vaccine comprised of a human DEC-205-NY-ESO-1 antibody that targets all human DCs. METHODS: Human anti-CLEC9A, anti-DEC-205 and isotype control IgG4 antibodies were genetically fused to NY-ESO-1 polypeptide. Cross-presentation to NY-ESO-1-epitope-specific CD8+ T cells and reactivity of T cell responses in patients with melanoma were assessed by interferon γ (IFNγ) production following incubation of CD141+ DCs and patient peripheral blood mononuclear cells with targeting antibodies. Humanized mice containing human DC subsets and a repertoire of naïve NY-ESO-1-specific CD8+ T cells were used to investigate naïve T cell priming. T cell effector function was measured by expression of IFNγ, MIP-1ß, tumor necrosis factor and CD107a and by lysis of target tumor cells. RESULTS: CLEC9A-NY-ESO-1 antibodies (Abs) were effective at mediating delivery and cross-presentation of multiple NY-ESO-1 epitopes by CD141+ DCs for activation of NY-ESO-1-specific CD8+ T cells. When benchmarked to NY-ESO-1 conjugated to an untargeted control antibody or to anti-human DEC-205, CLEC9A-NY-ESO-1 was superior at ex vivo reactivation of NY-ESO-1-specific T cell responses in patients with melanoma. Moreover, CLEC9A-NY-ESO-1 induced priming of naïve NY-ESO-1-specific CD8+ T cells with polyclonal effector function and potent tumor killing capacity in vitro. CONCLUSIONS: These data advocate human CLEC9A-NY-ESO-1 Ab as an attractive strategy for specific targeting of CD141+ DCs to enhance tumor immunogenicity in NY-ESO-1-expressing malignancies.
Assuntos
Antígenos de Neoplasias/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Células Dendríticas/imunologia , Lectinas Tipo C/metabolismo , Proteínas de Membrana/metabolismo , Receptores Mitogênicos/metabolismo , Trombomodulina/metabolismo , Animais , Feminino , Voluntários Saudáveis , Humanos , CamundongosRESUMO
OBJECTIVES: Sarcoma patients often undergo surveillance chest CT for detection of pulmonary metastases. No data exist on the optimal surveillance interval for chest CT. The aim of this study was to estimate pulmonary metastasis growth rate in sarcoma patients. METHODS: This was a retrospective review of 95 patients with pulmonary metastases (43 patients with histologically confirmed metastases and 52 with clinically diagnosed metastases) from sarcoma treated at an academic tertiary-care center between 01 January 2000 and 01 June 2019. Age, sex, primary tumor size, grade, subtype, size and volume of the pulmonary metastasis over successive chest CT scans were recorded. Two metastases per patient were chosen if possible. Multivariate linear mixed-effects models with random effects for each pulmonary metastasis and each patient were used to estimate pulmonary metastasis growth rate, evaluating the impact of patient age, tumor size, tumor grade, chemotherapy and tumor subtype. We estimated the pulmonary metastasis volume doubling time using these analyses. RESULTS: Maximal primary tumor size at diagnosis (LRT statistic = 2.58, df = 2, p = 0.275), tumor grade (LRT statistic = 1.13, df = 2, p = 0.567), tumor type (LRT statistic = 7.59, df = 6, p = 0.269), and patient age at diagnosis (LRT statistic = 0.735, df = 2, p = 0.736) were not statistically significant predictors of pulmonary nodule growth from baseline values. Chemotherapy decreased the rate of pulmonary nodule growth from baseline (LRT statistic = 7.96, df = 2, p = 0.0187). 95% of untreated pulmonary metastases are expected to grow less than 6 mm in 6.4 months. There was significant intrapatient and interpatient variation in pulmonary metastasis growth rate. Pulmonary metastasis volume growth rate was best fit with an exponential model in time. The volume doubling time for pulmonary metastases assuming an exponential model in time was 143 days (95% CI (104, 231) days). CONCLUSIONS: Assuming a 2 mm nodule is the smallest reliably detectable nodule by CT, the data suggest that an untreated pulmonary metastasis is expected to grow to 8 mm in 8.4 months (95% CI (4.9, 10.2) months). Tumor size, grade and sarcoma subtype did not significantly alter pulmonary metastasis growth rate. However, chemotherapy slowed the pulmonary metastasis growth rate. ADVANCES IN KNOWLEDGE: CT surveillance intervals for pulmonary metastases can be estimated based on metastasis growth rate. There was significant variation in the pulmonary metastasis growth rate between metastases within patient and between patients. Pulmonary nodule volume growth followed an exponential model, linear in time.
Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/secundário , Sarcoma/patologia , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
In several transgenic zebrafish models of hepatocellular carcinoma (HCC), hepatomegaly can be observed during early larval stages. Quantifying larval liver size in zebrafish HCC models provides a means to rapidly assess the effects of drugs and other manipulations on an oncogene-related phenotype. Here we show how to fix zebrafish larvae, dissect the tissues surrounding the liver, photograph livers using bright-field microscopy, measure liver area, and analyze results. This protocol enables rapid, precise quantification of liver size. As this method involves measuring liver area, it may underestimate differences in liver volume, and complementary methodologies are required to differentiate between changes in cell size and changes in cell number. The dissection technique described herein is an excellent tool to visualize the liver, gut, and pancreas in their natural positions for myriad downstream applications including immunofluorescence staining and in situ hybridization. The described strategy for quantifying larval liver size is applicable to many aspects of liver development and regeneration.
Assuntos
Fígado/anatomia & histologia , Peixe-Zebra/anatomia & histologia , Animais , Animais Geneticamente Modificados , Fixadores , Larva/anatomia & histologia , Fígado/diagnóstico por imagem , Microscopia/métodos , Tamanho do Órgão , Peixe-Zebra/genéticaRESUMO
All-optical helicity-dependent switching in ferromagnetic layers has revealed an unprecedented route to manipulate magnetic configurations by circularly polarized femtosecond laser pulses. In this work, rare-earth free synthetic ferrimagnetic heterostructures made from two antiferromagnetically exchange coupled ferromagnetic layers are studied. Experimental results, supported by numerical simulations, show that the designed structures enable all-optical switching which is controlled, not only by light helicity, but also by the relative Curie temperature of each ferromagnetic layer. Indeed, through the antiferromagnetic exchange coupling, the layer with the larger Curie temperature determines the final orientation of the other layer and so the synthetic ferrimagnet. For similar Curie temperatures, helicity-independent back switching is observed and the final magnetic configuration is solely determined by the initial magnetic state. This demonstration of electrically-detected, optical control of engineered rare-earth free heterostructures opens a novel route toward practical opto-spintronics.
RESUMO
BACKGROUND: One promising approach to influence nutrition behavior is to limit food and beverage marketing to children. Children are a lucrative market and schools may be an effective setting in which to intervene. Studies have shown that marketing in schools is prevalent but little is known about digital marketing (DM) to students in the school setting. METHODS: We used an online survey to assess DM environments in a national sample of middle schools. RESULTS: Our findings demonstrate that students are exposed to marketing through school devices. Gaps in school district, school and classroom policy and practice lead to student exposure to food and beverage marketing. CONCLUSIONS: Our data point to actionable policy and practice change at the school district, individual school, and classroom levels that could help limit unwanted and harmful food and beverage marketing to youth.