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1.
Phys Rev Lett ; 129(23): 235002, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36563220

RESUMO

We present two-dimensional turbulent electric field calculations via physics-informed deep learning consistent with (i) drift-reduced Braginskii theory under the framework of an axisymmetric fusion plasma with purely toroidal field and (ii) experimental estimates of the fluctuating electron density and temperature on open field lines obtained from analysis of gas puff imaging of a discharge on the Alcator C-Mod tokamak. The inclusion of effects from the locally puffed atomic helium on particle and energy sources within the reduced plasma turbulence model is found to strengthen correlations between the electric field and electron pressure. The neutrals are also directly associated with broadening the distribution of turbulent field amplitudes and increasing E×B shearing rates. This demonstrates a novel approach in plasma experiments by solving for nonlinear dynamics consistent with partial differential equations and data without encoding explicit boundary nor initial conditions.

2.
Ann Oncol ; 29(8): 1853-1860, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29982279

RESUMO

Background: Neoadjuvant anti-PD-1 may improve outcomes for patients with resectable NSCLC and provides a critical window for examining pathologic features associated with response. Resections showing major pathologic response to neoadjuvant therapy, defined as ≤10% residual viable tumor (RVT), may predict improved long-term patient outcome. However, %RVT calculations were developed in the context of chemotherapy (%cRVT). An immune-related %RVT (%irRVT) has yet to be developed. Patients and methods: The first trial of neoadjuvant anti-PD-1 (nivolumab, NCT02259621) was just reported. We analyzed hematoxylin and eosin-stained slides from the post-treatment resection specimens of the 20 patients with non-small-cell lung carcinoma who underwent definitive surgery. Pretreatment tumor biopsies and preresection radiographic 'tumor' measurements were also assessed. Results: We found that the regression bed (the area of immune-mediated tumor clearance) accounts for the previously noted discrepancy between CT imaging and pathologic assessment of residual tumor. The regression bed is characterized by (i) immune activation-dense tumor infiltrating lymphocytes with macrophages and tertiary lymphoid structures; (ii) massive tumor cell death-cholesterol clefts; and (iii) tissue repair-neovascularization and proliferative fibrosis (each feature enriched in major pathologic responders versus nonresponders, P < 0.05). This distinct constellation of histologic findings was not identified in any pretreatment specimens. Histopathologic features of the regression bed were used to develop 'Immune-Related Pathologic Response Criteria' (irPRC), and these criteria were shown to be reproducible amongst pathologists. Specifically, %irRVT had improved interobserver consistency compared with %cRVT [median per-case %RVT variability 5% (0%-29%) versus 10% (0%-58%), P = 0.007] and a twofold decrease in median standard deviation across pathologists within a sample (4.6 versus 2.2, P = 0.002). Conclusions: irPRC may be used to standardize pathologic assessment of immunotherapeutic efficacy. Long-term follow-up is needed to determine irPRC reliability as a surrogate for recurrence-free and overall survival.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Pulmão/patologia , Adulto , Antineoplásicos Imunológicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Viabilidade , Humanos , Ipilimumab/farmacologia , Ipilimumab/uso terapêutico , Pulmão/imunologia , Pulmão/cirurgia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Terapia Neoadjuvante/métodos , Neoplasia Residual , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Pneumonectomia , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Reprodutibilidade dos Testes , Resultado do Tratamento
3.
Breast Cancer Res Treat ; 171(2): 273-282, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29858752

RESUMO

PURPOSE: The purpose of the study was to evaluate protein expression of PD-L1 and CD20 as prognostic biomarkers of patient outcome in inflammatory breast cancer (IBC) samples. METHODS: PD-L1 and CD20 protein expression was measured by immunohistochemistry in 221 pretreatment IBC biopsies. PD-L1 was assessed in tumor cells (PD-L1+ tumor cells) and tumor stromal infiltrating lymphocytes (PD-L1+ TILs); CD20 was scored in tumor-infiltrating B cells. Kaplan-Meier curves and Cox proportional hazard models were used for survival analysis. RESULTS: PD-L1+ tumor cells, PD-L1+ TILs, and CD20+ TILs were found in 8%, 66%, and 62% of IBC, respectively. PD-L1+ tumor cells strongly correlated with high TILs, pathological complete response (pCR), CD20+ TILs, but marginally with breast cancer-specific survival (BCSS, P = 0.057). PD-L1+ TILs strongly correlated with high TILs, CD20+ TILs, and longer disease-free survival (DFS) in all IBC and in triple-negative (TN) IBC (P < 0.035). IBC and TN IBC patients with tumors containing both CD20+ TILs and PD-L1+ TILs (CD20+TILs/PD-L1+TILs) showed longer DFS and improved BCSS (P < 0.002) than patients lacking both, or those with either CD20+ TILs or PD-L1+ TILs alone. In multivariate analyses, CD20+TILs/PD-L1+TILs status was an independent prognostic factor for DFS in IBC (hazard ratio (HR): 0.53, 95% CI 0.37-0.77) and TN IBC (HR: 0.39 95% CI 0.17-0.88), and for BCSS in IBC (HR: 0.60 95% CI 0.43-0.85) and TN IBC (HR: 0.38 95% CI 0.17-0.83). CONCLUSION: CD20+TILs/PD-L1+TILs status represents an independent favorable prognostic factor in IBC and TN IBC, suggesting a critical role for B cells in antitumor immune responses. Anti-PD-1/PD-L1 and B cell-activating immunotherapies should be explored in these settings.


Assuntos
Antígenos CD20/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Antígeno B7-H1/metabolismo , Neoplasias Inflamatórias Mamárias/imunologia , Neoplasias Inflamatórias Mamárias/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Antígenos CD20/genética , Linfócitos B/patologia , Antígeno B7-H1/genética , Biomarcadores , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Inflamatórias Mamárias/mortalidade , Neoplasias Inflamatórias Mamárias/patologia , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/patologia , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
4.
Public Health ; 142: 22-30, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28057193

RESUMO

OBJECTIVE: In 2006, food industry self-regulatory efforts aimed to balance the mix of food advertisements to limit children's exposure to unhealthy food products. An update to these efforts proposed to eliminate all unhealthy advertisements during peak child viewing times and implement uniform nutrition criteria by December, 2013. Marketing techniques are not currently addressed in self-regulatory efforts. The food industry's pledge prompted researchers to conduct a content analysis to assess nutritional quality and presence of persuasive marketing techniques in child-directed food and beverage advertisements. STUDY DESIGN: Content analysis. METHODS: 32 h of children's television programming were recorded in February, 2013. Three independent coders assessed the nutritional content of food and beverage advertisements using the UK Nutrition Profiling System and assessed presence of persuasive techniques (PTs) using a rating form developed for this study. RESULTS: Overall, 13.75% of advertisements promoted a food or beverage product. Most food advertisements, 54.6%, represented unhealthy products and 95.48% of food advertisements contained at least one PT. The number of PTs was not significantly different for healthy (M = 4.98, SD = 2.07) and unhealthy food advertisements (M = 4.66, SD = 1.82) however food advertisements aimed at children used significantly more PTs (M = 5.5, SD = 1.43) than those targeting adults (M = 1.52, SD = 1.54), t (153) = 11.738, P < 0.0001. Saturday morning children's programming showed significantly fewer food advertisements compared to weekday morning children's programming. CONCLUSIONS: While a majority of food-related advertisements represented unhealthy items, advertisements airing during Saturday morning programming featured fewer food advertisements overall and were more frequently for healthier items compared to weekdays. Industry self-regulation may not be effective for reducing overall unhealthy ad exposure but may play a role in reduced exposure on weekends. Despite policy efforts, additional changes are needed to improve ad exposure experienced by children with a focus on addressing the persistent use of persuasive marketing techniques in food advertising intended for children.


Assuntos
Publicidade/estatística & dados numéricos , Alimentos , Marketing/métodos , Televisão , Bebidas , Criança , Dieta Saudável , Indústria Alimentícia , Humanos , Valor Nutritivo , Comunicação Persuasiva , Fatores de Tempo , Estados Unidos
5.
J Dairy Sci ; 99(11): 8802-8816, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27638259

RESUMO

Feeding saturated fatty acids may enhance milk yield in part by decreasing insulin sensitivity and shifting glucose utilization toward the mammary gland. Our objective was to evaluate the effects of palmitic acid (C16:0) on milk production and insulin sensitivity in cows. Twenty multiparous mid-lactation Holstein cows were enrolled in a study consisting of a 5-d covariate, 49-d treatment, and 14-d posttreatment period. All cows received a common sorghum silage-based diet and were randomly assigned to a diet containing no supplemental fat (control; n=10; 138±45d in milk) or C16:0 at 4% of ration DM (PALM; 98% C16:0; n=10; 136±44d in milk). Blood and milk were collected at routine intervals. Intravenous glucose tolerance tests (300mg/kg of body weight) were performed at d -1, 24, and 49 relative to start of treatment. Data were analyzed as repeated measures using a mixed model with fixed effects of treatment and time, and milk yield served as a covariate. The PALM treatment increased milk yield by wk 7. Furthermore, PALM increased milk fat yield and energy-corrected milk at wk 3 and 7. Changes in milk production occurred in parallel with enhanced energy intake. Increased milk fat yield during PALM treatment was due to increased C16:0 and C16:1 incorporation; PALM had no effect on concentration of milk components, BW, or body condition score. Two weeks posttreatment, energy-corrected milk and milk fat yield remained elevated in PALM-fed cows whereas yields of milk were similar between treatments. Increased milk fat yield after PALM treatment was due to increased de novo lipogenesis and uptake of preformed fatty acids. The basal concentration of nonesterified fatty acids (NEFA) in plasma increased by d 4, 6, and 8 of PALM treatment, a response not observed thereafter. Although PALM supplementation did not modify insulin, glucose, or triacylglycerol levels in plasma, total cholesterol in plasma was elevated by wk 3. Estimated insulin sensitivity was lower during the first week of PALM treatment; however, glucose disposal following glucose tolerance tests was not modified. In contrast, C16:0 feeding reduced glucose-stimulated NEFA disappearance by wk 7. Results demonstrate that increasing dietary energy from C16:0 for 7wk improves milk yield and milk composition without modifying systemic glucose tolerance. Reduced glucose-stimulated NEFA disappearance with C16:0 feeding and elevated circulating NEFA may reflect changes in adipose tissue insulin sensitivity.


Assuntos
Leite/metabolismo , Ácido Palmítico/metabolismo , Animais , Bovinos , Dieta/veterinária , Suplementos Nutricionais , Ácidos Graxos/metabolismo , Ácidos Graxos não Esterificados/sangue , Feminino , Glucose/metabolismo , Lactação
6.
J Dairy Sci ; 99(11): 8817-8830, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27638262

RESUMO

Reduced insulin action is a key adaptation that facilitates glucose partitioning to the mammary gland for milk synthesis and enhances adipose tissue lipolysis during early lactation. The progressive recovery of insulin sensitivity as cows advance toward late lactation is accompanied by reductions in circulating nonesterified fatty acids (NEFA) and milk yield. Because palmitic acid can promote insulin resistance in monogastrics through sphingolipid ceramide-dependent mechanisms, palmitic acid (C16:0) feeding may enhance milk production by restoring homeorhetic responses. We hypothesized that feeding C16:0 to mid-lactation cows would enhance ceramide supply and ceramide would be positively associated with milk yield. Twenty multiparous mid-lactation Holstein cows were enrolled in a study consisting of a 5-d covariate, 49-d treatment, and 14-d posttreatment period. All cows were randomly assigned to a sorghum silage-based diet containing no supplemental fat (control; n=10; 138±45 d in milk) or C16:0 at 4% of ration dry matter (PALM; 98% C16:0; n=10; 136±44 d in milk). Blood and milk were collected at routine intervals. Liver and skeletal muscle tissue were biopsied at d 47 of treatment. Intravenous glucose tolerance tests (300mg/kg of body weight) were performed at d -1, 24, and 49 relative to start of treatment. The plasma and tissue concentrations of ceramide and glycosylated ceramide were determined using liquid chromatography coupled with tandem mass spectrometry. Data were analyzed as repeated measures using a mixed model with fixed effects of treatment and time, and milk yield served as a covariate. The PALM treatment increased milk yield, energy-corrected milk, and milk fat yield. The most abundant plasma and tissue sphingolipids detected were C24:0-ceramide, C24:0-monohexosylceramide (GlcCer), and C16:0-lactosylceramide. Plasma concentrations of total ceramide and GlcCer decreased as lactation advanced, and ceramide and GlcCer were elevated in cows fed PALM. Palmitic acid feeding increased hepatic ceramide levels, a response not observed in skeletal muscle tissue. Plasma ceramides (e.g., C24:0-ceramide) were positively correlated with plasma NEFA and milk yield, and positively correlated with NEFA levels following a glucose challenge. Our data demonstrate a remodeled plasma and hepatic sphingolipidome in mid-lactation dairy cows fed PALM. The potential involvement in ceramide in homeorhetic nutrient partitioning to support lactation requires further consideration.


Assuntos
Ácidos Graxos não Esterificados/sangue , Leite/química , Tecido Adiposo/efeitos dos fármacos , Animais , Bovinos , Ceramidas , Dieta/veterinária , Ácidos Graxos , Feminino , Glucose/farmacologia , Insulina/sangue , Lactação , Ácido Palmítico/farmacologia
7.
Diabet Med ; 30(8): e233-8, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23586928

RESUMO

BACKGROUND: Maturity-onset diabetes of the young (MODY) caused by heterozygous mutations in the glucokinase (GCK) gene typically presents with lifelong, stable, mild fasting hyperglycaemia. With the exception of pregnancy, patients with GCK-MODY usually do not require pharmacological therapy. We report two unrelated patients whose initial genetic test results indicated a deletion of GCK exon 10, but whose clinical phenotypes were not typical of GCK-MODY. CASE REPORTS: In case 1, the patient was hyperglycaemic at diagnosis (glucose > 30 mmol/l) and elevated glucose levels > 10 mmol/l persisted after withdrawal of insulin therapy. The patient in case 2 was also hyperglycaemic at diagnosis [HbA1c > 86 mmol/mol (10%)], which improved with the introduction of oral hypoglycaemic agents. These clinical features were not consistent with GCK-MODY. Both patients had a single nucleotide variant that prevented multiplex ligation-dependent probe analysis, which generated a false positive result of a GCK exon 10 deletion. CONCLUSION: False positive genetic results in these two unrelated cases were attributable to the presence of a rare single nucleotide variant that prevented ligation of the probe in the multiplex ligation-dependent probe analysis kit used and falsely indicated deletion of exon 10 within GCK. Both cases had clinical features that did not tally with the typical GCK-MODY phenotype. These cases emphasize the need to interpret the results of definitive genetic tests within the specific clinical context. Increased medical sequencing is likely to lead to more reports of novel mutations of uncertain significance. If genetic investigations do not agree with the clinical picture, clinicians should exercise caution when making therapeutic changes based on these results.


Assuntos
Regiões 3' não Traduzidas , Diabetes Mellitus Tipo 2/genética , Glucoquinase/genética , Mutação , Adulto , Análise Mutacional de DNA , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Monitoramento de Medicamentos , Éxons , Reações Falso-Positivas , Feminino , Deleção de Genes , Glucoquinase/química , Humanos , Hiperglicemia/etiologia , Hiperglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Resultado do Tratamento , Adulto Jovem
8.
Rev Sci Instrum ; 93(6): 063504, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35778003

RESUMO

The role of turbulence in setting boundary plasma conditions is presently a key uncertainty in projecting to fusion energy reactors. To robustly diagnose edge turbulence, we develop and demonstrate a technique to translate brightness measurements of HeI line radiation into local plasma fluctuations via a novel integrated deep learning framework that combines neutral transport physics and collisional radiative theory for the 33D - 23P transition in atomic helium with unbounded correlation constraints between the electron density and temperature. The tenets for experimental validity are reviewed, illustrating that this turbulence analysis for ionized gases is transferable to both magnetized and unmagnetized environments with arbitrary geometries. Based on fast camera data on the Alcator C-Mod tokamak, we present the first two-dimensional time-dependent experimental measurements of the turbulent electron density, electron temperature, and neutral density, revealing shadowing effects in a fusion plasma using a single spectral line.

9.
Phys Rev E ; 104(2-2): 025205, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34525532

RESUMO

One of the most intensely studied aspects of magnetic confinement fusion is edge plasma turbulence which is critical to reactor performance and operation. Drift-reduced Braginskii two-fluid theory has for decades been widely applied to model boundary plasmas with varying success. Towards better understanding edge turbulence in both theory and experiment, we demonstrate that a physics-informed deep learning framework constrained by partial differential equations can accurately learn turbulent fields consistent with the two-fluid theory from partial observations of electron pressure which is not otherwise possible using conventional equilibrium models. This technique presents a paradigm for the advanced design of plasma diagnostics and validation of magnetized plasma turbulence theories in challenging thermonuclear environments.

10.
Domest Anim Endocrinol ; 74: 106517, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739764

RESUMO

Inadequate milk production by sows often limits the growth of piglets. A successful lactation requires prolactin (PRL)-induced differentiation of the alveolar epithelium within the mammary glands of sows between days 90-110 of gestation. We hypothesized that induction of late gestational hyperprolactinemia in primiparous sows by oral administration of the dopamine antagonist metoclopramide (MET) would enhance mammary epithelial differentiation, milk yield, and piglet growth rate and that these effects would carry over into a subsequent lactation. Twenty-six gilts were assigned to receive either MET (n = 13, 0.8 mg/kg) or vehicle (CON, n = 13) twice daily from days 90-110 of gestation. The same sows were followed into their second lactation without additional treatment. On day 90 of gestation, circulating PRL concentrations peaked 45 min after feeding MET (P < 0.001) and then returned to baseline 3 h later. This response occurred daily out to day 104 of gestation (P < 0.05). Compared with CON, MET-treated gilts had enlarged alveoli on gestation day 110 (P < 0.05). Treatment with MET did not affect feed intake, body weight, or body fatness during pregnancy or lactation. Piglets born to MET-treated sows had both increased body weights and average daily gain on lactation days 14 and 21 (P < 0.05). Milk intake by piglets was estimated from deuterium oxide dilution. Although milk intake by piglets nursing MET sows was not statistically different from those nursing CON sows on day 21 of lactation (P = 0.18), there was a greater increase in milk consumption by piglets born to MET-treated sows between days 9 and 21 of lactation than for those in CON litters (P < 0.001). In one group of second parity sows (n = 11) that were treated with MET during their first gestation, milk yield increased by 21% during their second lactation (P < 0.05) in association with a 14% decline in body fatness across lactation compared with a 7% decline in CON sows (P < 0.05). These findings demonstrate that MET-induced hyperprolactinemia in primiparous sows during late pregnancy can increase milk yield and piglet growth rate, setting the stage for further large-scale studies.


Assuntos
Animais Recém-Nascidos/crescimento & desenvolvimento , Lactação/efeitos dos fármacos , Metoclopramida/administração & dosagem , Prolactina/sangue , Sus scrofa/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Peso Corporal , Antagonistas dos Receptores de Dopamina D2/administração & dosagem , Feminino , Idade Gestacional , Paridade , Projetos Piloto , Gravidez , Prolactina/fisiologia
12.
Int J Obes (Lond) ; 33(3): 305-16, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19153582

RESUMO

OBJECTIVE: To examine the effect of an intensive lifestyle weight loss intervention (ILI) compared to diabetes support and education (DSE) on changes in fitness and physical activity in the Look AHEAD trial. DESIGN: Randomized clinical trial to compare a lifestyle intervention for weight loss with a DSE condition in individuals with type 2 diabetes. SUBJECTS: Data from 4376 overweight or obese adults with type 2 diabetes (age=58.7+/-6.8 years, body mass index (BMI)=35.8+/-5.8 kg/m(2)) who completed 1 year of the Look AHEAD trial and had available fitness data were analyzed. INTERVENTION: Subjects were randomly assigned to DSE or ILI. DSE received standard care plus three education sessions over the 1-year period. ILI included individual and group contact throughout the year, restriction in energy intake and 175 min per week of prescribed physical activity. MEASUREMENTS: Fitness was assessed using a submaximal graded exercise test. Physical activity was assessed by questionnaire in a subset of 2221 subjects. RESULTS: Change in fitness was statistically greater in ILI vs DSE after adjustment for baseline fitness (20.9 vs 5.7%; P<0.0001). Multivariate analysis showed that change in fitness was greater in overweight vs obese Class II and III (P<0.05). Physical activity increased by 892+/-1694 kcal per week in ILI vs 108+/-1254 kcal per week in DSE (P<0.01). Changes in fitness (r=0.41) and physical activity (r=0.42) were significantly correlated with weight loss (P<0.0001). CONCLUSIONS: The ILI was effective in increasing physical activity and improving cardiorespiratory fitness in overweight and obese individuals with type 2 diabetes. This effect may add to weight loss in improving metabolic control in patients in lifestyle intervention programs.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/terapia , Angiopatias Diabéticas/prevenção & controle , Obesidade/terapia , Aptidão Física , Redução de Peso/fisiologia , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Exercício Físico/fisiologia , Teste de Esforço , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/complicações , Obesidade/fisiopatologia , Comportamento de Redução do Risco , Inquéritos e Questionários
14.
Domest Anim Endocrinol ; 66: 14-20, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30205268

RESUMO

Prolactin controls mammary development as well as the lactogenic and galactopoietic processes in sows and increasing prolactin during gestation can augment milk yield. The dopamine receptor antagonist domperidone can increase circulating prolactin concentrations in pigs, but the ideal dose to achieve sustained hyperprolactinemia remains unknown. An experiment was performed to develop a protocol for using domperidone in studies of rapid and sustained hyperprolactinemia in late-pregnant gilts. On day 90 of gestation, gilts were divided into 4 groups: (1) intramuscular (IM) injections of canola oil (3 mL, controls [CTL], n = 9), (2) IM injections with 0.1 mg/kg BW of domperidone (low [LO], n = 8), (3) IM injections with 0.5 mg/kg BW of domperidone (medium [ME], n = 11), and (4) IM injections with 1.0 mg/kg BW of domperidone (high [HI], n = 11). Injections were given daily at 8:05 from days 90 to 109 of gestation. Treated gilts also received domperidone per os (0.5 mg/kg BW) at 8:00 and 20:00 on days 89, 90, and 91 of gestation. Three jugular blood samples were collected from all gilts at 6-h intervals on days 89, 90, and 91 of gestation, then twice daily on days 92, 93, and 94. Thereafter, samples were obtained at 8:00 every other day until day 114 of gestation. Blood was sampled serially from 9 CTL and 11 HI gilts on days 89 and 94 of gestation. On day 89 of gestation, prolactin concentrations for LO, ME, and HI gilts increased within 6 h of domperidone per os (P < 0.001). From days 89 until 93 of gestation, the area under the curve (AUC) for LO, ME, and HI gilts was greater than that for CTL gilts (P < 0.001), whereas from days 89 until 114, ME and HI gilts had greater AUC than CTL and LO gilts (P < 0.05). Results demonstrate that the combination of per os treatment with IM injections of 0.5 mg/kg of domperidone in an oil emulsion leads to the rapid and sustained release of prolactin over 24 d in late-pregnant gilts. Higher doses of domperidone failed to further increase circulating prolactin levels. These findings provide a useful strategy to induce sustained hyperprolactinemia in late-pregnant gilts.


Assuntos
Domperidona/administração & dosagem , Hiperprolactinemia/induzido quimicamente , Prolactina/sangue , Sus scrofa , Animais , Relação Dose-Resposta a Droga , Emulsões , Feminino , Idade Gestacional , Injeções Intramusculares/veterinária , Lactação/efeitos dos fármacos , Lactação/fisiologia , Leite/química , Gravidez , Óleo de Brassica napus
15.
Animal ; 13(11): 2547-2555, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31104643

RESUMO

Reductions in insulin sensitivity in periparturient dairy cows develop as a means to support lactation; however, excessive mobilization of fatty acids (FA) increases the risk for peripartal metabolic disorders. Our objectives were to investigate the effect of prepartum body condition score (BCS) on systemic glucose and insulin tolerance, and to compare direct and indirect measurements of insulin sensitivity in peripartal lean and overweight dairy cows. Fourteen multiparous Holstein cows were allocated into two groups according to their BCS at day -28 prepartum: lean (n = 7; BCS ≤ 3.0) or overweight; (n = 7; BCS ≥ 4.0). Liver biopsies were performed on day -27, -14 and 4, relative to expected parturition. Intravenous insulin or glucose tolerances tests were performed following each liver biopsy. Relative to lean cows, overweight cows exhibited lower dry matter intake, lost more BCS and displayed increased plasma FA and ß-hydroxybutyrate concentrations and elevated liver lipid content during peripartum. Glucose clearance rate was lower for all cows postpartum. Prepartum BCS had minimal effects on insulin and glucose tolerance; however, the ability of the cow to restore blood glucose levels following an insulin challenge was suppressed by increased BCS. Glucose-dependent parameters of insulin and glucose tolerance were not correlated with surrogate indices of insulin sensitivity. We conclude that prepartum BCS had minimal effect on systemic insulin sensitivity following parturition. The observed inconsistency between surrogate indices of insulin sensitivity and direct measurements of insulin and glucose tolerance adds support to growing concerns regarding their usefulness as tools to estimate systemic insulin action in periparturient cows.


Assuntos
Bovinos/fisiologia , Glucose/fisiologia , Insulina/fisiologia , Lactação/fisiologia , Período Periparto/fisiologia , Ácido 3-Hidroxibutírico/sangue , Animais , Ácidos Graxos/farmacologia , Ácidos Graxos não Esterificados/sangue , Ácidos Graxos não Esterificados/metabolismo , Feminino , Teste de Tolerância a Glucose/veterinária , Humanos , Insulina/administração & dosagem , Insulina/sangue , Resistência à Insulina , Lipídeos/análise , Fígado/efeitos dos fármacos , Fígado/patologia , Parto , Período Pós-Parto , Gravidez
16.
Br Dent J ; 233(6): 441, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36151151
17.
Artigo em Inglês | MEDLINE | ID: mdl-34188348

RESUMO

PURPOSE: Atherosclerosis detection remains challenging in coronary CT angiography for patients with cardiac implants. Pacing electrodes of a pacemaker or lead components of a defibrillator can create substantial blooming and streak artifacts in the heart region, severely hindering the visualization of a plaque of interest. We present a novel reconstruction method that incorporates a deformable model for metal leads to eliminate metal artifacts and improve anatomy visualization even near the boundary of the component. METHODS: The proposed reconstruction method, referred as STF-dKCR, includes a novel parameterization of the component that integrates deformation, a 3D-2D preregistration process that estimates component shape and position, and a polyenergetic forward model for x-ray propagation through the component where the spectral properties are jointly estimated. The methodology was tested on physical data of a cardiac phantom acquired on a CBCT testbench. The phantom included a simulated vessel, a metal wire emulating a pacing lead, and a small Teflon sphere attached to the vessel wall, mimicking a calcified plaque. The proposed method was also compared to the traditional FBP reconstruction and an interpolation-based metal correction method (FBP-MAR). RESULTS: Metal artifacts presented in standard FBP reconstruction were significantly reduced in both FBP-MAR and STF-dKCR, yet only the STF-dKCR approach significantly improved the visibility of the small Teflon target (within 2 mm of the metal wire). The attenuation of the Teflon bead improved to 0.0481 mm-1 with STF-dKCR from 0.0166 mm-1 with FBP and from 0.0301 mm-1 with FBP-MAR - much closer to the expected 0.0414 mm-1. CONCLUSION: The proposed method has the potential to improve plaque visualization in coronary CT angiography in the presence of wire-shaped metal components.

18.
Int J Food Microbiol ; 257: 247-253, 2017 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-28704728

RESUMO

The purpose of this study was to develop a novel and robust molecular assay for the detection of human pathogenic yersiniae (i.e. Yersinia enterocolitica, Y. pseudotuberculosis and Y. pestis) in complex food samples. The assay combines multiplexed real-time PCR (qPCR) and Pyrosequencing for detecting and differentiating human pathogenic yersiniae with high confidence through sequence based confirmation. The assay demonstrated 100% specificity and inclusivity when tested against a panel of 14 Y. enterocolitica, 22 Y. pestis, 24 Y. pseudotuberculosis and a diverse selection of 17 other non-Yersinia bacteria. Pyrosequencing reads ranged from 28 to 40bp in length and had 94-100% sequence identity to the correct species in the GenBank nr database. Microbial enrichments of 48 ready-to-eat foods collected in the Greater Toronto Area from March 2014 to May 2014, including 46 fresh sprout and 2 salad products, were then tested using the assay. All samples were negative for Y. pestis and Y. pseudotuberculosis. Both salads (n=2) and 35% of sprout products (n=46) including 7.1% of alfalfa sprouts (n=14), 81% of bean sprouts (n=16), 12% of mixed sprouts (n=8) tested positive for Y. enterocolitica which was not detected in broccoli sprouts (n=5), onion sprouts (n=1), and pea sprouts (n=2). Cycle thresholds (Ct) of positive samples for Y. enterocolitica were between 23.0 and 37.9 suggesting post enrichment concentrations of approximately 1×102 to 1×106Y. enterocolitica per 1mL of enriched broth. An internal amplification control which was coamplified with targets revealed PCR inhibition in five samples which was resolved following a one in ten dilution. Pyrosequencing of qPCR amplicons suggests monoclonality and revealed a single nucleotide polymorphism that is present in Y. enterocolitica biotype 1A suggesting low pathogenicity of the detected strains. This study is the first to combine Pyrosequencing and qPCR for the detection of human pathogenic yersiniae and is applicable to a broad range of complex samples including ready-to-eat food samples.


Assuntos
Contaminação de Alimentos/análise , Microbiologia de Alimentos/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Yersinia enterocolitica/isolamento & purificação , Yersinia pestis/isolamento & purificação , Yersinia pseudotuberculosis/isolamento & purificação , Sequência de Bases , DNA Bacteriano/genética , Fast Foods/microbiologia , Humanos , Polimorfismo de Nucleotídeo Único/genética , Análise de Sequência de DNA , Especificidade da Espécie , Verduras/microbiologia , Yersinia enterocolitica/genética , Yersinia enterocolitica/patogenicidade , Yersinia pestis/genética , Yersinia pseudotuberculosis/genética
19.
Proc SPIE Int Soc Opt Eng ; 101322017 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-28603335

RESUMO

Acquisition of CT images with comparable diagnostic power can potentially be achieved with lower radiation exposure than the current standard of care through the adoption of hardware-based fluence-field modulation (e.g. dynamic bowtie filters). While modern CT scanners employ elements such as static bowtie filters and tube-current modulation, such solutions are limited in the fluence patterns that they can achieve, and thus are limited in their ability to adapt to broad classes of patient morphology. Fluence-field modulation also enables new applications such as region-of-interest imaging, task specific imaging, reducing measurement noise or improving image quality. The work presented in this paper leverages a novel fluence modulation strategy that uses "Multiple Aperture Devices" (MADs) which are, in essence, binary filters, blocking or passing x-rays on a fine scale. Utilizing two MAD devices in series provides the capability of generating a large number of fluence patterns via small relative motions between the MAD filters. We present the first experimental evaluation of fluence-field modulation using a dual-MAD system, and demonstrate the efficacy of this technique with a characterization of achievable fluence patterns and an investigation of experimental projection data.

20.
J Biomed Opt ; 11(1): 014018, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16526895

RESUMO

A low-cost, fast, and noninvasive method for early diagnosis of malignant lesions of oral mucosa based on diffuse reflectance spectral signatures is presented. In this technique, output of a tungsten halogen lamp is guided to the tissue through the central fiber of a reflection probe whose surrounding six fibers collects tissue reflectance. Ex vivo diffuse reflectance spectra in the 400 to 600-nm region is measured from surgically removed oral cavity lesions using a miniature fiber optic spectrometer connected to a computer. Reflectance spectral intensity is higher in malignant tissues and shows dips at 542 and 577 nm owing to absorption from oxygenated hemoglobin (HbO2). Measurements carried out, within an hour of surgical excision, on malignant lesion and adjoining uninvolved mucosa show that these absorption features are more prominent in neoplastic tissues owing to increased microvasculature and blood content. It is observed that reflectance intensity ratio of hemoglobin bands, R540/R575, from malignant sites are always lower than that from normal sites and vary according to the histological grade of malignancy. The diffuse reflectance intensity ratio R540/R575 of the hemoglobin bands appears to be a useful tool to discriminate between malignant lesions and normal mucosa of the oral cavity in a clinical setting.


Assuntos
Biomarcadores Tumorais/análise , Diagnóstico por Computador/métodos , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/metabolismo , Proteínas de Neoplasias/análise , Oxiemoglobinas/análise , Fotometria/métodos , Análise Espectral/métodos , Humanos , Neoplasias Bucais/classificação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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