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1.
Ultrasound Obstet Gynecol ; 64(1): 36-43, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38339776

RESUMO

OBJECTIVE: Although remarkable strides have been made in fetal medicine and the prenatal diagnosis of congenital heart disease, around 60% of newborns with isolated coarctation of the aorta (CoA) are not identified prior to birth. The prenatal detection of CoA has been shown to have a notable impact on survival rates of affected infants. To this end, implementation of artificial intelligence (AI) in fetal ultrasound may represent a groundbreaking advance. We aimed to investigate whether the use of automated cardiac biometric measurements with AI during the 18-22-week anomaly scan would enhance the identification of fetuses that are at risk of developing CoA. METHODS: We developed an AI model capable of identifying standard cardiac planes and conducting automated cardiac biometric measurements. Our data consisted of pregnancy ultrasound image and outcome data spanning from 2008 to 2018 and collected from four distinct regions in Denmark. Cases with a postnatal diagnosis of CoA were paired with healthy controls in a ratio of 1:100 and matched for gestational age within 2 days. Cardiac biometrics obtained from the four-chamber and three-vessel views were included in a logistic regression-based prediction model. To assess its predictive capabilities, we assessed sensitivity and specificity on receiver-operating-characteristics (ROC) curves. RESULTS: At the 18-22-week scan, the right ventricle (RV) area and length, left ventricle (LV) diameter and the ratios of RV/LV areas and main pulmonary artery/ascending aorta diameters showed significant differences, with Z-scores above 0.7, when comparing subjects with a postnatal diagnosis of CoA (n = 73) and healthy controls (n = 7300). Using logistic regression and backward feature selection, our prediction model had an area under the ROC curve of 0.96 and a specificity of 88.9% at a sensitivity of 90.4%. CONCLUSIONS: The integration of AI technology with automated cardiac biometric measurements obtained during the 18-22-week anomaly scan has the potential to enhance substantially the performance of screening for fetal CoA and subsequently the detection rate of CoA. Future research should clarify how AI technology can be used to aid in the screening and detection of congenital heart anomalies to improve neonatal outcomes. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Coartação Aórtica , Inteligência Artificial , Coração Fetal , Ultrassonografia Pré-Natal , Humanos , Feminino , Coartação Aórtica/diagnóstico por imagem , Coartação Aórtica/embriologia , Gravidez , Ultrassonografia Pré-Natal/métodos , Coração Fetal/diagnóstico por imagem , Coração Fetal/embriologia , Idade Gestacional , Biometria/métodos , Curva ROC , Sensibilidade e Especificidade , Dinamarca , Recém-Nascido , Adulto , Estudos de Casos e Controles , Valor Preditivo dos Testes
3.
Eur J Endocrinol ; 177(2): 157-168, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28522646

RESUMO

BACKGROUND: Men with type 2 diabetes mellitus (T2D) often have lowered testosterone levels and an increased risk of cardiovascular disease (CVD). Ectopic fat increases the risk of CVD, whereas subcutaneous gluteofemoral fat protects against CVD and has a beneficial adipokine-secreting profile. HYPOTHESIS: Testosterone replacement therapy (TRT) may reduce the content of ectopic fat and improve the adipokine profile in men with T2D. DESIGN AND METHODS: A randomized, double-blinded, placebo-controlled study in 39 men aged 50-70 years with T2D and bioavailable testosterone levels <7.3 nmol/L. Patients were randomized to TRT (n = 20) or placebo gel (n = 19) for 24 weeks. Thigh subcutaneous fat area (TFA, %fat of total thigh volume), subcutaneous abdominal adipose tissue (SAT, % fat of total abdominal volume) and visceral adipose tissue (VAT, % fat of total abdominal volume) were measured by magnetic resonance (MR) imaging. Hepatic fat content was estimated by single-voxel MR spectroscopy. Adiponectin and leptin levels were measured by in-house immunofluorometric assay. Coefficients (b) represent the placebo-controlled mean effect of intervention. RESULTS: TFA (b = -3.3 percentage points (pp), P = 0.009), SAT (b = -3.0 pp, P = 0.006), levels of adiponectin (b = -0.4 mg/L, P = 0.045), leptin (b = -4.3 µg/mL, P < 0.001), leptin:adiponectin ratio (b = -0.53, P = 0.001) and HDL cholesterol (b = -0.11 mmol/L, P = 0.009) decreased during TRT compared with placebo. Hepatic fat content and VAT were unchanged. CONCLUSIONS: The effects of TRT on cardiovascular risk markers were ambiguous. We observed potentially harmful changes in cardiovascular risk parameters, markedly reduced subcutaneous fat and unchanged ectopic fat during TRT and a reduction in adiponectin levels. On the other hand, the decrease in leptin and leptin:adiponectin ratio assessments could reflect an amelioration of the cardiovascular risk profile linked to hyperleptinaemia in ageing men with T2D.


Assuntos
Adiponectina/sangue , Diabetes Mellitus Tipo 2/sangue , Leptina/sangue , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Testosterona/administração & dosagem , Idoso , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Terapia de Reposição Hormonal/métodos , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade
4.
Nanoscale ; 8(21): 11002-11, 2016 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-27174233

RESUMO

Development of safe and efficient radiotherapy routines requires quantification of the delivered absorbed dose to the cancer tissue in individual patients. In vivo dosimetry can provide accurate information about the absorbed dose delivered during treatment. In the current study, a novel silver-nanosensor formulation based on poly(vinylpyrrolidinone)-coated silver nanoparticles formulated in a gelation matrix composed of sucrose acetate isobutyrate has been developed for use as an in vivo dosimeter for external beam radiotherapy. In situ photonuclear reactions trigger the formation of radioactive (106)Ag, which enables post treatment verification of the delivered dose using positron emission tomography imaging. The silver-nanosensor was investigated in a tissue equivalent thorax phantom using clinical settings and workflow for both standard fractionated radiotherapy (2 Gy) and stereotactic radiotherapy (10- and 22 Gy) in a high-energy beam setting (18 MV). The developed silver-nanosensor provided high radiopacity on the planning CT-scans sufficient for patient positioning in image-guided radiotherapy and provided dosimetric information about the absorbed dose with a 10% and 8% standard deviation for the stereotactic regimens, 10 and 22 Gy, respectively.


Assuntos
Dosimetria in Vivo , Nanopartículas Metálicas , Tomografia por Emissão de Pósitrons , Radioterapia , Prata , Humanos , Posicionamento do Paciente , Imagens de Fantasmas
5.
Am J Physiol Endocrinol Metab ; 305(4): E496-506, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23800880

RESUMO

Physical exercise increases peripheral insulin sensitivity, but regional differences are poorly elucidated in humans. We investigated the effect of aerobic exercise training on insulin-stimulated glucose uptake in five individual femoral muscle groups and four different adipose tissue regions, using dynamic (femoral region) and static (abdominal region) 2-deoxy-2-[¹8F]fluoro-d-glucose (FDG) PET/CT methodology during steady-state insulin infusion (40 mU·m⁻²·min⁻¹). Body composition was measured by dual X-ray absorptiometry and MRI. Sixty-one healthy, sedentary [V(O2max) 36(5) ml·kg⁻¹·min⁻¹; mean(SD)], moderately overweight [BMI 28.1(1.8) kg/m²], young [age: 30(6) yr] men were randomized to sedentary living (CON; n = 17 completers) or moderate (MOD; 300 kcal/day, n = 18) or high (HIGH; 600 kcal/day, n = 18) dose physical exercise for 11 wk. At baseline, insulin-stimulated glucose uptake was highest in femoral skeletal muscle followed by intraperitoneal visceral adipose tissue (VAT), retroperitoneal VAT, abdominal (anterior + posterior) subcutaneous adipose tissue (SAT), and femoral SAT (P < 0.0001 between tissues). Metabolic rate of glucose increased similarly (~30%) in the two exercise groups in femoral skeletal muscle (MOD 24[9, 39] µmol·kg⁻¹·min⁻¹, P = 0.004; HIGH 22[9, 35] µmol·kg⁻¹·min⁻¹, P = 0.003) (mean[95% CI]) and in five individual femoral muscle groups but not in femoral SAT. Standardized uptake value of FDG decreased ~24% in anterior abdominal SAT and ~20% in posterior abdominal SAT compared with CON but not in either intra- or retroperitoneal VAT. Total adipose tissue mass decreased in both exercise groups, and the decrease was distributed equally among subcutaneous and intra-abdominal depots. In conclusion, aerobic exercise training increases insulin-stimulated glucose uptake in skeletal muscle but not in adipose tissue, which demonstrates some interregional differences.


Assuntos
Tecido Adiposo Branco/metabolismo , Exercício Físico , Transportador de Glucose Tipo 4/metabolismo , Glucose/metabolismo , Resistência à Insulina , Músculo Esquelético/metabolismo , Sobrepeso/terapia , Tecido Adiposo Branco/diagnóstico por imagem , Tecido Adiposo Branco/efeitos dos fármacos , Adiposidade , Adulto , Transporte Biológico/efeitos dos fármacos , Índice de Massa Corporal , Meios de Contraste/metabolismo , Fluordesoxiglucose F18/metabolismo , Técnica Clamp de Glucose , Transportador de Glucose Tipo 4/biossíntese , Humanos , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Insulina/farmacologia , Estudos Longitudinais , Masculino , Imagem Multimodal , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/efeitos dos fármacos , Sobrepeso/metabolismo , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Regulação para Cima , Adulto Jovem
6.
Phys Rev Lett ; 86(26 Pt 1): 5994-7, 2001 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-11415412

RESUMO

The dispersion of the low-energy magnetic excitations of the Pr sublattice in PrBa(2)Cu(3)O(6.2) is determined by inelastic neutron scattering measurements on a single crystal. The dispersion, which shows the effect of interactions with the Cu spin waves, is well described by a model of the coupled Cu-Pr magnetic system. This model enables values for the principal exchange constants to be determined. The results suggest that both Pr-Pr and Cu-Pr interactions are important in producing the anomalously high ordering temperature of the Pr sublattice. Measurements of the Cu optic spin wave mode show that the interlayer Cu-Cu exchange is significantly lower than in YBa(2)Cu(3)O(6.2).

7.
J Med Chem ; 24(3): 285-9, 1981 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7265114

RESUMO

The syntheses of the methyl ester, butyl ester, (ethoxycarbonyl)methyl ester, and 11 (acyloxy)methyl esters of the potent gamma-aminobutyric acid agonist isoguvacine (1,2,3,6-tetrahydropyridine-4-carboxylic acid) and described. The chemical stability of the esters and their in vitro rates of hydrolysis under approximately physiological conditions by nonspecific esterases from human serum were examined. A selected number of the esters were tested for antagonism of convulsions induced by bicuculline, isoniazide, and by electroschock. While in the compounds showed only weak activities in the bicuculline and isoniazide tests, a good correlation between in vitro rates of enzymatic hydrolysis and the time of onset of the antagonism of the electroschock-induced convulsions could be found.


Assuntos
Anticonvulsivantes/síntese química , Ácidos Isonicotínicos/síntese química , Animais , Anticonvulsivantes/farmacologia , Estabilidade de Medicamentos , Ésteres , Humanos , Hidrólise , Camundongos
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